bluuebunny/crossref_metadata_2025_split huggingface dataset:
Confrontment and solution to gonadotropin resistance and low oocyte retrieval in in vitro fertilization for type I BPES: a case series with review of literature
Authors: Yu Yiqi , Ji Mengxia , Xu Weihai , Zhang Ling , Qi Ming , Shu Jing 
Published: October 2021

Abstract
Background
FOXL2 mutations in human cause Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES). While type II BPES solely features eyelid abnormality, type I BPES involves not only eyelid but also ovary, leading to primary ovarian insufficiency (POI) and female infertility. Current mainstream reproductive option for type I BPES is embryo or oocyte donation. Attempts on assisted reproductive technology (ART) aiming biological parenthood in this population were sparse and mostly unsuccessful.

Case presentation
Two Chinese type I BPES patients with low anti-müllerian hormone (AMH) and elevated follicle stimulating hormone (FSH) presented with primary infertility in their early 30s. Genetic studies confirmed two heterozygous duplication mutations that were never reported previously in East Asian populations. They received in vitro fertilization (IVF) treatment and both exhibited resistance to gonadotropin and difficulty in retrieving oocytes in repeated cycles. Doubled to quadrupled total gonadotropin doses were required to awaken follicular response. Patient 1 delivered a baby girl with the same eyelid phenotype and patient 2 had ongoing live intrauterine pregnancy at the time of manuscript submission.

Conclusions
This is the second reported live birth of biological offspring in type I BPES patients, and first success using IVF techniques. It confirmed that ART is difficult but feasible in type I BPES. It further alerts clinicians and genetic counsellors to type female BPES patients with caution in view of the precious and potentially narrowed reproductive window.
Cocultured porcine granulosa cells respond to excess non-esterified fatty acids during in vitro maturation
Authors: Shi Meihong , Sirard Marc-André 
Published: October 2021

Abstract
Background
Non-esterified fatty acids (NEFAs) are one of the main lipid components of follicular fluid at concentrations that depend on circulating levels. Elevated levels of NEFAs impair oocyte quality, development potential, and may subsequently influence the metabolism and reproductive fitness of offspring. Granulosa cells (GCs) are the follicular cells that are closely communicating with the oocyte. However, the responses of GCs exposed to high levels of NEFAs when cocultured with cumulus-oocyte complexes (COCs), and how they attenuate the negative effects of NEFAs on oocytes, are unclear.

Results
To better understand this protective effect, monolayers of porcine GCs were cocultured with COCs during in vitro maturation (IVM) in the presence of elevated levels of NEFAs. Genomic expression analysis was conducted to explore the responses of the GCs to the elevated levels of NEFAs. After limma algorithm analysis, 1,013 genes were differentially expressed between GCs cultured with and without elevated NEFAs. Among them, 438 genes were upregulated and 575 were downregulated. The differentially expressed genes were enriched in pathways related to metabolism, inflammation, and epithelial-mesenchymal transition.

Conclusions
The pathways and upstream regulators suggested that the cocultured GCs responded to the elevated NEFAs with (1) inhibition of the transition from granulosa to luteal cell, (2) interactions of metabolism change, anti-inflammation, mitochondrial function, and cell transition, (3) intercommunication with cocultured COCs of anti-inflammatory factors.
Massive parallel sequencing in individuals with multiple primary tumours reveals the benefit of re-analysis
Authors: Wallander Karin , Thonberg Håkan , Nilsson Daniel , Tham Emma 
Published: October 2021

AbstractMultiple primary cancers, defined as three or more primary tumours, are rare, and there are few genetic studies concerning them. There is a need for increased knowledge on the heritability of multiple primary cancers and genotype-phenotype correlations. We have performed whole-genome/exome sequencing (WGS/WES) in ten individuals with three or more primary tumours, with no previous findings on standard clinical genetic investigations. In one individual with a clinical diagnosis of MEN1, a likely pathogenic cryptic splice site variant was detected in the MEN1 gene. The variant (c.654C > A) is synonymous but we showed in a cDNA analysis that it affects splicing and leads to a frameshift, with the theoretical new amino acid sequence p.(Gly219Glufs*13). In one individual with metachronous colorectal cancers, ovarian cancer, endometrial cancer and chronic lymphocytic leukaemia, we found a likely pathogenic variant in the MLH1 gene (c.27G > A), and two risk factor variants in the genes CHEK2 and HOXB13. The MLH1 variant is synonymous but has previously been shown to be associated to constitutional low-grade hypermethylation of the MLH1 promoter, and segregates with disease in families with colorectal and endometrial cancer. No pathogenic single nucleotide or structural variants were detected in the remaining eight individuals in the study. The pathogenic variants found by WGS/WES were in genes already sequenced by Sanger sequencing and WES in the clinic, without any findings. We conclude that, in individuals with an unequivocal clinical diagnosis of a specific hereditary cancer syndrome, where standard clinical testing failed to detect a causative variant, re-analysis may lead to a diagnosis.
Using motivational interviewing combined with digital shoe-fitting to improve adherence to wearing orthopedic shoes in people with diabetes at risk of foot ulceration: study protocol for a cluster-randomized controlled trial
Authors: Jongebloed-Westra M. , Bode C. , van Netten J. J. , ten Klooster P. M. , Exterkate S. H. , Koffijberg H. , van Gemert-Pijnen J. E. W. C. 
Published: October 2021

Abstract
Background
Diabetic foot ulcers have a high impact on mobility and daily functioning and lead to high treatment costs, for example, by hospitalization and amputation. To prevent (re)ulcerations, custom-made orthopedic shoes are considered essential. However, adherence to wearing the orthopedic shoes is low, and improving adherence was not successful in the past. We propose a novel care approach that combines motivational interviewing (MI) with a digital shoe-fitting procedure to improve adherence to orthopedic shoes. The aim of this trial is to assess the (cost-)effectiveness of this novel care approach compared to usual care (no MI and casting-based shoe-fitting) in promoting footwear adherence and ulcer prevention.

Methods
The trial will include people with diabetes, with IWGDF Risk categories 1–3, who have been prescribed orthopedic shoes. Participants will be randomized at the level of the podiatrist to the novel care approach or usual care. The primary outcome is the proportion of participants who adhere to the use of their orthopedic shoes, that is, who take at least 80% of their total daily steps with orthopedic shoes. A temperature microsensor will be built into the participants’ orthopedic shoes to measure wearing time continuously over 12 months. In addition, daily activity will be measured periodically using log data with an activity monitor. Data from the temperature microsensor and activity monitor will be combined to calculate adherence. (Re-)experienced complications after receiving orthopedic shoes will be registered. Questionnaires and interviews will measure the experiences of participants regarding orthopedic shoes, experiences of podiatrists regarding motivational interviewing, care consumption, and quality of life. Differences in costs and quality of life will be determined in a cost-effectiveness analysis.

Discussion
This trial will generate novel insights into the socio-economic and well-being impact and the clinical effectiveness of the novel care approach on adherence to wearing orthopedic shoes.

Trial registration
Netherlands Trial Register NL7710. Registered on 6 May 2019
Design, computational studies, synthesis and in vitro antimicrobial evaluation of benzimidazole based thio-oxadiazole and thio-thiadiazole analogues
Authors: Noureldin Nada A. , Richards Jennifer , Kothayer Hend , Baraka Mohammed M. , Eladl Sobhy M. , Wootton Mandy , Simons Claire 
Published: October 2021

Abstract
Background
Two series of benzimidazole based thio-oxadiazole and thio-thiadiazole analogues were designed and synthesised as novel antimicrobial drugs through inhibition of phenylalanyl-tRNA synthetase (PheRS), which is a promising antimicrobial target. Compounds were designed to mimic the structural features of phenylalanyl adenylate (Phe-AMP) the PheRS natural substrate.

Methods
A 3D conformational alignment for the designed compounds and the PheRS natural substrate revealed a high level of conformational similarity, and a molecular docking study indicated the ability of the designed compounds to occupy both Phe-AMP binding pockets. A molecular dynamics (MD) simulation comparative study was performed to understand the binding interactions with PheRS from different bacterial microorganisms. The synthetic pathway of the designed compounds proceeded in five steps starting from benzimidazole. The fourteen synthesised compounds 5a-d, 6a-c, 8a-d and 9a-c were purified, fully characterised and obtained in high yield.

Results
In vitro antimicrobial evaluation against five bacterial strains showed a moderate activity of compound 8b with MIC value of 32 μg/mL against S. aureus, while all the synthesised compounds showed weak activity against both E. faecalis and P. aeruginosa (MIC 128 μg/mL).

Conclusion
Compound 8b provides a lead compound for further structural development to obtain high affinity PheRS inhibitors.
Factors influencing mass drug administration adherence and community drug distributor opportunity costs in Liberia: a mixed-methods approach
Authors: Agboraw Efundem , Sosu Fred , Dean Laura , Siakeh Alice , Thomson Rachael , Kollie Karsor , Worrall Eve 
Published: October 2021

Abstract
Background
Preventive chemotherapy delivered via mass drug administration (MDA) is essential for the control of neglected tropical diseases (NTDs), including lymphatic filariasis (LF), schistosomiasis and onchocerciasis. Successful MDA relies heavily on community drug distributor (CDD) volunteers as the interface between households and the health system. This study sought to document and analyse demand-side (households) and supply-side (health system) factors that affect MDA delivery in Liberia.

Methods
Working in two purposively selected counties, we conducted a household MDA access and adherence survey; a CDD survey to obtain information on direct and opportunity costs associated with MDA work; an observational survey of CDDs; and key informant surveys (KIS) with community-level health workers. Data from the CDD survey and Liberian minimum wage rates were used to calculate the opportunity cost of CDD participation per MDA round. The observational data were used to calculate the time spent on individual household-level tasks and CDD time costs per house visited. KIS data on the organisation and management of the MDA in the communities, and researcher reflections of open-ended survey responses were thematically analysed to identify key demand- and supply-side challenges.

Results
More respondents were aware of MDA than NTD in both counties. In Bong, 39% (103/261) of respondents reported taking the MDA tablet in the last round, with “not being informed” as the most important reason for non-adherence. In Maryland, 56% (147/263) reported taking MDA with “being absent” at the time of distribution being important for non-adherence. The mean cost per CDD of participating in the MDA round was −$11.90 (median $5.04, range −$169.62 to $30.00), and the mean time per household visited was 17.14 min which equates to a mean opportunity cost of $0.03 to $0.05 per household visited. Thematic analysis identified challenges, including shortages of and delays in medicine availability; CDD frustration over costs; reporting challenges; and household concerns about drug side effects.

Conclusions
Improved adherence to MDA and subsequent elimination of NTDs in Liberia would be supported by an improved medicine supply chain, financial compensation for CDDs, improved training, healthcare workforce strengthening, greater community involvement, capacity building, and community awareness.

Graphical Abstract
Novel temporal and spatial patterns of metastatic colonization from breast cancer rapid-autopsy tumor biopsies
Authors: Huang Xiaomeng , Qiao Yi , Brady Samuel W. , Factor Rachel E. , Downs-Kelly Erinn , Farrell Andrew , McQuerry Jasmine A. , Shrestha Gajendra , Jenkins David , Johnson W. Evan , Cohen Adam L. , Bild Andrea H. , Marth Gabor T. 
Published: October 2021

Abstract
Background
Metastatic breast cancer is a deadly disease with a low 5-year survival rate. Tracking metastatic spread in living patients is difficult and thus poorly understood.

Methods
Via rapid autopsy, we have collected 30 tumor samples over 3 timepoints and across 8 organs from a triple-negative metastatic breast cancer patient. The large number of sites sampled, together with deep whole-genome sequencing and advanced computational analysis, allowed us to comprehensively reconstruct the tumor’s evolution at subclonal resolution.

Results
The most unique, previously unreported aspect of the tumor’s evolution that we observed in this patient was the presence of “subclone incubators,” defined as metastatic sites where substantial tumor evolution occurs before colonization of additional sites and organs by subclones that initially evolved at the incubator site. Overall, we identified four discrete waves of metastatic expansions, each of which resulted in a number of new, genetically similar metastasis sites that also enriched for particular organs (e.g., abdominal vs bone and brain). The lung played a critical role in facilitating metastatic spread in this patient: the lung was the first site of metastatic escape from the primary breast lesion, subclones at this site were likely the source of all four subsequent metastatic waves, and multiple sites in the lung acted as subclone incubators. Finally, functional annotation revealed that many known drivers or metastasis-promoting tumor mutations in this patient were shared by some, but not all metastatic sites, highlighting the need for more comprehensive surveys of a patient’s metastases for effective clinical intervention.

Conclusions
Our analysis revealed the presence of substantial tumor evolution at metastatic incubator sites in a patient, with potentially important clinical implications. Our study demonstrated that sampling of a large number of metastatic sites affords unprecedented detail for studying metastatic evolution.
Language of transducer manipulation 2.0: continuing to codify terms for effective teaching
Authors: End Bradley , Prats Michael I. , Minardi Joseph , Sharon Melinda , Bahner David P. , Boulger Creagh T. 
Published: October 2021

Abstract
Objectives
Accurate communication is an integral component of ultrasound education. In light of the recent global pandemic, this has become even more crucial as many have moved to virtual education out of necessity. Several studies and publications have sought to establish common terminology for cardinal ultrasound probe motions. To date, no studies have been performed to determine which of these terms have been adopted by the ultrasound community at large.

Methods
A survey was developed which asked respondents to describe videos of six common probe motions in addition to providing basic demographic and training data. The survey was disseminated electronically across various academic listservs and open access resources.

Results
Data were collected over a 6-week period and yielded 418 unique responses. Responses demonstrated significant variation in terminology related to all 6 cardinal probe motions. While some degree of difference in response can be accounted for by discipline of training, inter-group variation still exists in terminology to describe common probe motions. Of the survey respondents, 57.5% felt that inconsistent probe motion terminology made teaching ultrasound more difficult.

Conclusions
The results demonstrate that despite efforts to codify probe motions, variation still exists between ultrasound practitioners and educators in the description of cardinal probe motions. This lack of consensus can contribute to challenges in both virtual and in-person ultrasound education.
High sleep quality can increase the performance of CrossFit® athletes in highly technical- and cognitive-demanding categories
Authors: Klier Kristina , Dörr Selina , Schmidt Annette 
Published: October 2021

Abstract
Background
In current sports science, the important role of sleep quality for health and peak performance is well acknowledged. More precisely, it is evident that the negative combination of stressful factors, low resources, and bad sleep habits causes short-term performance losses as well as long-term health consequences. As the maximization of human performance consisting of multiple fixed workloads is the main motivation in CrossFit® (CF), the aim of the present study was to investigate the influence of high sleep quality on performance in CrossFit® athletes (CFA) and the different training categories that are addressed in CF.

Methods
In total, 149 CFA (81 females, 68 males; 32.01 ± 7.49 years old, 2.56 ± 1.77 active years in CF) filled in the online survey comprising the Pittsburgh Sleep Quality Index (PSQI) and CF performance-specific questions.

Results
It was found that CFA with high sleep quality reported higher values in all performance-related outcomes. Especially in Hero-/Girl-Workouts (χ2 = (1, n = 83) = 9.92, p = .002, φ = 0.37) and Gymnastics (χ2 = (1, n = 129) = 8.74, p = .003, φ = 0.28), performance differed significantly between good and poor sleeping CFA. Since those CF categories are highly technical- and cognitive-demanding high sleep quality seems to play a fundamental role in complex motor skill learning and performance development.

Conclusions
These results reveal for the first time the positive effects of high sleep quality for performance in CFA and could be used as basis for future studies. Future research should also develop and empirically test suitable interventions to foster high sleep quality in CFA.
Trial Registration: The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of University of the Federal Armed Forces Munich, Germany (06/04/2018).
Controllability of higher-order fractional damped stochastic systems with distributed delay
Authors: Arthi G. , Suganya K. , Ma Yong-Ki 
Published: October 2021

AbstractIn this paper, the controllability analysis is proposed for both linear and nonlinear higher-order fractional damped stochastic dynamical systems with distributed delay in Hilbert spaces which involve fractional Caputo derivative of different orders. Based on the properties of fractional calculus, the fixed point technique, and the construction of controllability Gramian matrix, we establish the controllability results for the considered systems. Finally, examples are constructed to illustrate the applicability of obtained results.
Reflecting on perceived failure of entrepreneurship development initiatives to help ignite economic development in Malawi
Authors: Mwatsika Charles 
Published: October 2021

AbstractThis study reflects on the perceived failure of entrepreneurship development initiatives to help ignite economic development in Malawi. A cross-sectional survey of 337 enterprises collected top-of-the-mind definitions of entrepreneurship, and innovations and their values carried out. Content analyses, comparison of mean values, 2 independent samples tests and multiple linear regression analyses showed that entrepreneurship is perceived as starting and managing one’s own business; being self-employed. Carrying out innovations is low and of low value, but enterprises which carried out innovations had higher median values than those that did not. The study found opportunity-motivated, growth-oriented, limited liability enterprises in the medium-to-large size category to be productive types of enterprises, but there were very few. It is argued that initiatives fail to help ignite economic development because knowledge which guides entrepreneurship development misses the essence of entrepreneurship—carrying out innovations. Secondly, there are no initiatives to support SME innovation and growth through product development, investments in modern production facilities and access to export markets. It is encouraged that key stakeholders adjust their understanding of entrepreneurship to neoclassical economic perspectives, encourage innovative start-ups and provide support to grow the numbers of productive enterprises.
Differentiating brucella spondylitis from tuberculous spondylitis by the conventional MRI and MR T2 mapping: a prospective study
Authors: Guo Hui , Lan Siqin , He Yuanlin , Tiheiran Maijudan , Liu Wenya 
Published: October 2021

Abstract
Background
Brucella spondylitis (BS) and tuberculous spondylitis (TS), caused initially by bacteremia, are the two leading types of granulomatous spinal infections. BS is easy to miss or may be misdiagnosed as TS. Our purpose aims to differentiate BS from TS in conventional MR imaging and MR T2 mapping.

Methods
We performed on 26 BS and 27 TS patients conventional MR imaging and MR T2 mapping. We analyzed the features in conventional MR imaging and measured T2 values of the lesion vertebrae (LV) and unaffected adjacent vertebrae (UAV) in BS and TS patients, respectively.

Results
There were no significant differences in sex, age, national between BS and TS. There was significantly lower severity of vertebral destruction, vertebral posterior convex deformity, dead bone, and abscess scope in BS when compared to TS (p  <  0.001, p  =  0.048, p  <  0.001, p  <  0.001, respectively). The vertebral hyperplasia was significantly higher in BS when compared to TS (p  <  0.001). The T2 value of the LV with BS was markedly higher than that in the UAV with BS and that in the LV and UAV with TS (p  <  0.001, p  <  0.037, p  <  0.001, respectively). The T2 value of the LV with TS was significantly higher than that of the UAV in TS and BS (p  <  0.001, p  <  0.001, respectively). There were no significant differences in the T2 value of the UAV between BS and TS (p  =  0.568).

Conclusions
The qualitative and quantitative evaluation may differentiate BS from TS. The conventional MR imaging helps to distinguish BS from TS by several distinctive features. MR T2 mapping has the additional potential to provide quantitative information between BS and TS.