bluuebunny/crossref_metadata_2025 huggingface dataset:
Prolonged response to treatment based on cell-free DNA analysis and molecular profiling in three patients with metastatic cancer: a case series
Authors: Naqvi Mohammad Faraz , Vo Henry Hiep , Vining David , Tsimberidou Apostolia-Maria
Published: March 2021

Background:

Patients with advanced and/or metastatic solid tumors have limited treatment options. Mutations that serve as biomarkers of carcinogenesis can be found in cell-free DNA of patients’ plasma. Analysis of circulating tumor DNA (ctDNA) was developed as a non-invasive, cost-effective alternative to tumor biopsy when such biopsy is not technically feasible or it is associated with high risk for complications. The role of ctDNA in precision oncology is promising but its clinical significance across tumor types remains to be validated. We report a case series of three heavily pretreated patients with advanced solid tumors who received matched targeted therapy based on ctDNA analysis and/or tumor molecular profiling.

Case presentation:

Three patients with advanced, metastatic cancer and the following characteristics are presented: a 71-year-old woman with ovarian cancer and BRCA2 mutation identified in ctDNA and tumor tissue was treated with a PARP inhibitor and achieved partial response by RECIST (Response Evaluation Criteria in Solid Tumors) for 22.6+ months; a 40-year-old woman with adenoid cystic carcinoma of the parotid gland was treated with a MEK/RAF pathway inhibitor on the basis of RAF1 amplification on ctDNA analysis and had stable disease for 20.2 months; and a 56-year-old woman with breast cancer and a BRCA1 mutation identified by ctDNA analysis was treated with a PARP inhibitor and achieved stable disease for 9.1 months. All three patients are alive at the time of this report.

Conclusions:

These results suggest that ctDNA analysis can contribute to selection of targeted therapy in patients with advanced, metastatic cancer. Prospective clinical trials to evaluate and optimize ctDNA biomarkers, as well as the integration of novel and/or alternative targeted therapies, are warranted to fully assess the role of ctDNA analysis in cancer therapy.

Trial registration:

www.clinicaltrials.gov (NCT02152254). Registered May 28, 2014. https://www.clinicaltrials.gov/ct2/show/NCT02152254 . MD Anderson protocol # PA12-1161 (approval ID IRB1 FWA00000121) and # PA11-0377 (approval ID IRB4 FWA00005015).
Building eConsult (Electronic Consults) Capability at an Academic Medical Center to Improve Efficiencies in Delivering Specialty Care
Authors: Thompson Matthew A. , Fuhlbrigge Anne L. , Pearson Duane W. , Saxon David R. , Oberst-Walsh Linda A. , Thomas John F.
Published: March 2021

As the COVID-19 health crisis continues to reshape healthcare, systems across the country face increasing pressure to adapt their models of care to expand access to care, while also improving efficiency and quality in the face of limited resources. Consequently, many have shown a growing interest and receptivity to the expansion of telehealth models to help meet these demands. Electronic consultations (eConsults) are a telehealth modality that allow for a non-face-to-face asynchronous consultation between a primary care provider (PCP) and a specialist aimed at facilitating specialist input without the need for a patient visit. The aim of this case study is to describe eConsults, how they differ from traditional in person models of care and other models of telemedicine and to review the evidence related to the effectiveness of eConsults by PCPs and clinicians from multiple specialties at the University of Colorado School of Medicine. We have worked to develop an infrastructure, delivery system integration, and care model adaptations that aim to improve delivery system performance by ensuring proper care in appropriate settings and lowering costs through reduced utilization. Lastly, we have increased care coordination, improved collaboration and better care transitions through strengthening of relationships between community-based PCPs and academic medical center-based specialists. This work has resulted in cost savings to patients and positive provider satisfaction.
Does Facet Distraction Affect Patient Outcomes After ACDF?
Authors: Karamian Brian A. , Levy Hannah A. , Canseco Jose A. , Goyal Dhruv K. C. , Divi Srikanth N. , Lee Joseph K. , Kurd Mark F. , Rihn Jeffrey A. , Hilibrand Alan S. , Kepler Christopher K. , Vaccaro Alexander R. , Schroeder Gregory D.
Published: March 2021

Study Design:

Retrospective cohort study

Objective:

The aim of this study is to determine if there is a correlation between the amount of facet distraction and postoperative patient-reported outcomes after ACDF.

Methods:

A retrospective cohort analysis of patients undergoing 1 to 3 level ACDF for degenerative pathologies at a single academic center was performed. Each patient received upright, lateral cervical spine x-rays at the immediate postoperative time point from which interfacet distance (facet distraction) was measured. Patient-reported outcome measures including NDI, PCS-12, MCS-12, VAS Neck, and VAS Arm pain scores were obtained preoperatively and at short-term (<3 months) and long-term (>1 year) follow-up. Receiver operating curves were generated to evaluate the possibility of a critical interfacet distraction distance. Univariate and multivariate analysis were performed to compare outcomes between groups based on the degree of facet distraction.

Results:

A total of 229 patients met the inclusion criteria. Receiver operating curves failed to yield a critical interfacet distraction distance associated with worse post-operative outcomes. Patients were instead grouped based on facet distraction distance below and above the third quartile (0.8mm-2.0 mm, 2.0mm-3.7 mm), with 173 and 56 patients in each respective group. Univariate analysis did not detect any statistically significant differences in outcome measures, recovery ratio, or % MCID achievement at short- and long-term follow-up between groups. Multivariate analysis also failed to demonstrate any significant differences between the facet distraction groups.

Conclusion:

Increased interfacet distance did not correlate with increased neck pain or disability after an ACDF.
Impact of COVID-19 on Recovered Athletes Returning to Competitive Play in the NBA “Bubble”
Authors: Vaudreuil Nicholas J. , Kennedy Amy J. , Lombardo Stephen J. , Kharrazi F. Daniel
Published: March 2021

Background:

The global pandemic caused by COVID-19 has had far-reaching implications for the world of professional sports. The National Basketball Association (NBA) suspended active regular season play in 2020 after a player tested positive for SARS-CoV-2. No previous studies have examined the impact of COVID-19 on return to play in the NBA.

Purpose/Hypothesis:

The purpose of this study was to examine performance measures for NBA players who had recovered from COVID-19 and returned to play in the NBA bubble. We hypothesized that these athletes would play fewer minutes and have decreased performance statistics compared with performance during the 2019-2020 regular season prior to the lockdown and with career averages.

Study Design:

Case series; Level of evidence, 4.

Methods:

NBA players positive for SARS-CoV-2 who played in both the 2019-2020 regular season and the NBA bubble were identified. Data collected included player demographics and player performance statistics.

Results:

A total of 20 players were included in the study. Players who had recovered from COVID-19 played significantly fewer minutes per game in the NBA bubble (25.8 vs 28.7; P = .04) and made fewer field goals per game (4.6 vs 5.4; P = .02) compared with the season prior to shutdown. While NBA bubble players demonstrated slight decreases in averages for points ( P = .06), rebounds ( P =.13), assists ( P = .23), steals ( P = .30), and blocks ( P = .71) per game, these were not statistically significant. Aside from an increase in made free throws per game during the bubble (3.3 vs 2.8; P = .04), player performance was not significantly different from career averages.

Conclusion:

For players who tested positive for SARS-CoV-2 prior to playing in the NBA bubble, the current study demonstrated that despite playing significantly fewer minutes per game, performance was not statistically different from either their pre-COVID 2019-2020 level of play or from their career averages.
Providing Home-Based Support for Children with Chronic Conditions in an Urban Slum: Experiences from a Community-Based Palliative Care Program in Bangladesh
Authors: Chowdhury Mostofa Kamal , Shopna Khadija , Lynch-Godrei Anisha , Jain Mehr , Farheen Nadia , Begum Noorjahan , Ahmad Nezamuddin , Doherty Megan
Published: March 2021

We describe the palliative care needs of children with chronic conditions and their caregivers in an urban slum in Bangladesh. In this cross-sectional study, we interviewed 25 caregivers whose children receive support from a community-based program lead by community health workers, that provides medication, medical supplies, food, caregiver training, and psychological support free of charge. The chronic conditions of children in the program included cerebral palsy (80%), congenital heart disease (8%), neurodegenerative conditions (4%), cancer (4%), and intellectual disabilities (4%). Common symptoms included cough or breathing problems (64%), fever (56%), and pain (56%). Most caregivers (96%) reported they were unable to do any paid work due to their child’s needs and in all families, the child’s condition had a significant impact on their financial situation. Community-based palliative care programs can be developed to support children with chronic conditions who may not access care from acute care facilities.
Always on, never done? How the mind recovers after a stressful workday?
Authors: Wendsche Johannes , de Bloom Jessica , Syrek Christine , Vahle-Hinz Tim
Published: March 2021

Many workers experience their jobs as effortful or even stressful, which can result in strain. Although recovery from work would be an adaptive strategy to prevent the adverse effects of work-related strain, many workers face problems finding enough time to rest and to mentally disconnect from work during nonwork time. What goes on in workers’ minds after a stressful workday? What is it about their jobs that makes them think about their work? This special issue aims to bridge the gap between research on recovery processes mainly examined in Occupational Health Psychology, and research on work stress and working hours, often investigated in the field of Human Resource Management. We first summarize conceptual and theoretical streams from both fields of research. In the following, we discuss the contributions of the five special issue papers and conclude with key messages and directions for further research.
Agent-based simulation of short-term peer-to-peer rentals: Evidence from the Amsterdam housing market
Authors: Overwater Arnold , Yorke-Smith Neil
Published: March 2021

Gentrification, displacement and social exclusion are hot topics of debate in the city of Amsterdam, the Netherlands. A current phenomena is short-term rentals of private homes. In its peer-to-peer form, this phenomena has grown sharply, facilitated by services such as Airbnb. Its growth has caused controversies among communities in touristic areas of Amsterdam, since it contributes to a changed social fabric, increased housing prices and overall gentrification. In the Netherlands and elsewhere, municipal and national policy makers are interested to regulate short-term rentals. In order to provide insights into qualitative policy effects, we develop a micro-level agent-based simulation. Our spatial model simulates residential migration based on income and house pricing. The underlying economic theory is that of Smith’s rent-gap hypothesis. Our model is among the first agent-based approaches investigating this type of rental market, and the first to model a specific housing market, including social housing, in a geographically accurate way. Simulation analysis shows that the touristic rental market has caused considerable changes in housing prices and population development. We find that more lower income citizens remain in the city centre when regulation of the market is stronger, and that banning the touristic market restrains the overall increase in house prices, compared to the business-as-usual scenario. However, the feasibility of enforcement of regulation, and its libertarian consequences, must be considered.
We Do Big Things From Very Little: The Well-being of Rural Neighbourhood House Employees and Volunteers
Authors: Binder Marley J. , Barrett Elizabeth , Beattie Jessica
Published: March 2021

Neighbourhood houses are under increased pressure to demonstrate their value, contributing to rising stress and potentially psychological harm. This research aims to understand what effect working within the rural neighbourhood house sector has on employee and volunteer well-being. A phenomenological methodology was employed using semi-structured interviews. The qualitative interview data were analysed thematically to elicit emergent themes. Participants described how involvement in the sector both positively and negatively influenced their well-being. The two major themes, with associated sub-themes, that emerged from the participant interviews were: (a) ‘interconnectedness and community’; and (b) ‘burnout and stress’. Rural Australians have poorer health outcomes, with these often exacerbated through increased physical-work demands, family conflict and poor mental health. Rural neighbourhood houses are important organisations that engage and connect with those that may be disadvantaged, but this often comes at a cost to those who operate these vital services. A myriad of factors, including funding, isolation, unpaid work hours and lack of support, negatively contribute to the participants’ well-being. The article suggests solutions to improve the well-being of rural neighbourhood house employees and volunteers.
Optimization of molding process parameters for CF/PEEK composites based on Taguchi method
Authors: Dai Guangming , Zhan Lihua , Guan Chenglong , Huang Minghui
Published: March 2021

In this article, nine groups of laminates were prepared according to the Taguchi L9(33) test array to study the influence of three process parameters, including molding pressure, molding temperature, and holding time on the performance of unidirectional carbon fiber/polyetheretherketone (CF/PEEK) laminates. A differential scanning calorimetry test was employed to select a reasonable process parameters range. The transverse tensile strength of the laminates was measured, and the fiber–matrix interfacial bonding behavior of the tested samples was analyzed by scanning electron microscopy. The results showed that the significance of factors to transverse tensile strength were molding temperature, holding time, and molding pressure in sequence. The optimal molding process parameters for CF/PEEK composite laminate were molding temperature of 400°C, molding pressure of 3 MPa, and holding time of 30 min. The optimization results were meaningful for the extension and application of thermoplastic composites.
Protecting providers and patients: results of an Internet survey of health care workers’ risk perceptions and ethical concerns during the COVID-19 pandemic
Authors: O’Neal Lauren , Heisler Michele , Mishori Ranit , Haar Rohini J.
Published: March 2021

Background

The COVID-19 pandemic has generated worldwide scarcity of critical resources to protect against and treat disease. Shortages of face masks and other protective equipment place health workers, already on the frontline of the disease, at higher risk. Moral distress from making difficult decisions about allocating scarce resources and care to patients ill with COVID-19 can further add to burdens health workers face. This study investigates clinical health workers’ risk perceptions and concerns about the ethics of their clinical decision-making, the actions of their institutions to address resource scarcity concerns during the COVID-19 pandemic, and their ability to voice safety concerns, as well as their own views on how scarce resources should be allocated.

Methods

An online survey was open to health care workers who provide clinical care to patients, with no specialty training or geographic location requirements, from May 19 to June 30, 2020. Participants were recruited through purposive sampling using medical association and institutional email lists, and by snowball sampling.

Results

Of 839 participants, a majority were physicians (540, 69.4%) working in academic medical centers (270, 35.2%) or private health systems in the community (234, 30.5%) in the USA (760, 90.7%). Most reported being concerned about their own health (494, 73.6%) and about the possibility of spreading COVID-19 to family and friends (534, 85.9%) during the pandemic. All respondents reported shortages or rationing of at least one type of medical resource (e.g., sanitizing supplies and personal protective equipment). More than half of respondents (351, 53.9%) did not feel they received sufficient training in how to allocate scarce resources in the pandemic. Many felt moral distress related to conflicts between institutional constraints and what they believed was right (459, 66.5%). Though a majority (459, 67.7%) reported feeling “comfortable” internally communicating with their administration about safety issues, far fewer reported feeling “confident” speaking publicly about safety issues without retaliation from their institution (255, 37.3%).

Conclusions

In the face of limited resources, surveyed health care workers reported concern about their own and their families’ health from exposure. Securing adequate protective equipment must be a high priority for pandemic management. In addition, more governmental and facility-level ethical guidance is required for allocation of resources given ongoing scarcity, and facilities must create conditions so health care workers can speak openly about safety issues without fear of retaliation.
Mitochondrial genotype alters the impact of rapamycin on the transcriptional response to nutrients in Drosophila
Authors: Santiago John C. , Boylan Joan M. , Lemieux Faye A. , Gruppuso Philip A. , Sanders Jennifer A. , Rand David M.
Published: March 2021

Background

In addition to their well characterized role in cellular energy production, new evidence has revealed the involvement of mitochondria in diverse signaling pathways that regulate a broad array of cellular functions. The mitochondrial genome (mtDNA) encodes essential components of the oxidative phosphorylation (OXPHOS) pathway whose expression must be coordinated with the components transcribed from the nuclear genome. Mitochondrial dysfunction is associated with disorders including cancer and neurodegenerative diseases, yet the role of the complex interactions between the mitochondrial and nuclear genomes are poorly understood.

Results

Using a Drosophila model in which alternative mtDNAs are present on a common nuclear background, we studied the effects of this altered mitonuclear communication on the transcriptomic response to altered nutrient status. Adult flies with the ‘native’ and ‘disrupted’ genotypes were re-fed following brief starvation, with or without exposure to rapamycin, the cognate inhibitor of the nutrient-sensing target of rapamycin (TOR). RNAseq showed that alternative mtDNA genotypes affect the temporal transcriptional response to nutrients in a rapamycin-dependent manner. Pathways most greatly affected were OXPHOS, protein metabolism and fatty acid metabolism. A distinct set of testis-specific genes was also differentially regulated in the experiment.

Conclusions

Many of the differentially expressed genes between alternative mitonuclear genotypes have no direct interaction with mtDNA gene products, suggesting that the mtDNA genotype contributes to retrograde signaling from mitochondria to the nucleus. The interaction of mitochondrial genotype (mtDNA) with rapamycin treatment identifies new links between mitochondria and the nutrient-sensing mTORC1 (mechanistic target of rapamycin complex 1) signaling pathway.
Dynamic transcriptome analysis identifies genes related to fatty acid biosynthesis in the seeds of Prunus pedunculata Pall
Authors: Bao Wenquan , Ao Dun , Wang Lin , Ling Zhihao , Chen Maoshan , Bai Yue , Wuyun Ta-Na , Chen Junxing , Zhang Shuning , Li Fengming
Published: March 2021

Background

Prunus pedunculata Pall, the deciduous shrub of Amygdalus subgenus in Rosaceae, is a new kind of desert oil-bearing tree. It has a long story of being planted in the West and North of China for sand fixation and desert control. In addition, the seeds of P. pedunculata are rich of oil, especially the monounsaturated fatty acid and polyunsaturated fatty acid. However, little is known about the molecular mechanisms of oil accumulation during the seed development of P. pedunculata.

Results

The seeds of P. pedunculata from three independent plants at 10, 18, 24, 31, 39, 45, 59 and 73 days after flowering (DAF) were obtained and the oil compositions were evaluated. It showed that oleic acid was the dominant type of oil content in the mature seeds (from 32.724% at 10DAF to 72.06% at 73DAF). Next, transcriptome sequencing for the developing seeds produced 988.795 million high quality reads and TRINITY assembled 326,271 genes for the first transcriptome for P. pedunculata. After the assembled transcriptome was evaluated by BUSCO with 85.9% completeness, we identified 195,342, 109,850 and 121,897 P. pedunculata genes aligned to NR, GO and KEGG pathway databases, respectively. Then, we predicted 23,229 likely proteins from the assembled transcriptome and identified 1917 signal peptides and 5512 transmembrane related proteins. In the developing seeds we detected 91,362 genes (average FPKM > 5) and correlation analysis indicated three possible development stages – early (10 ~ 24DAF), middle (31 ~ 45DAF) and late (59 ~ 73DAF). We next analyzed the differentially expressed genes (DEGs) in the developing seeds. Interestingly, compared to 10DAF the number of DEGs was increased from 4406 in 18DAF to 27,623 in 73DAF. Based on the gene annotation, we identified 753, 33, 8 and 645 DEGs related to the fatty acid biosynthesis, lipid biosynthesis, oil body and transcription factors. Notably, GPAT, DGD1, LACS2, UBC and RINO were highly expressed at the early development stage, ω6-FAD, SAD, ACP, ACCA and AHG1 were highly expressed at the middle development stage, and LACS6, DGD1, ACAT1, AGPAT, WSD1, EGY2 and oleosin genes were highly expressed at the late development stage.

Conclusions

This is the first time to study the developing seed transcriptome of P. pedunculata and our findings will provide a valuable resource for future studies. More importantly, it will improve our understanding of molecular mechanisms of oil accumulation in P. pedunculata.
Isolation and characterizations of a novel recombinant scFv antibody against exotoxin A of Pseudomonas aeruginosa
Authors: Shadman Zahra , Farajnia Safar , Pazhang Mohammad , Tohidkia Mohammadreza , Rahbarnia Leila , Najavand Saeed , Toraby Sayna
Published: March 2021

Background

Pseudomonas aeruginosa is the leading cause of nosocomial infections, especially in people with a compromised immune system. Targeting virulence factors by neutralizing antibodies is a novel paradigm for the treatment of antibiotic-resistant pseudomonas infections. In this respect, exotoxin A is one of the most potent virulence factors in P. aeruginosa. The present study was carried out to identify a novel human scFv antibody against the P. aeruginosa exotoxin A domain I (ExoA-DI) from a human scFv phage library.

Methods

The recombinant ExoA-DI of P. aeruginosa was expressed in E. coli, purified by Ni-NTA column, and used for screening of human antibody phage library. A novel screening procedure was conducted to prevent the elimination of rare specific clones. The phage clone with high reactivity was evaluated by ELISA and western blot.

Results

Based on the results of polyclonal phage ELISA, the fifth round of biopanning leads to the isolation of several ExoA-DI reactive clones. One positive clone with high affinity was selected by monoclonal phage ELISA and used for antibody expression. The purified scFv showed high reactivity with the recombinant domain I and full-length native exotoxin A.

Conclusions

The purified anti-exotoxin A scFv displayed high specificity against exotoxin A. The human scFv identified in this study could be the groundwork for developing a novel therapeutic agent to control P. aeruginosa infections.
Subacute cerebellar ataxia following respiratory symptoms of COVID-19: a case report
Authors: Werner Jana , Reichen Ina , Huber Michael , Abela Irene A. , Weller Michael , Jelcic Ilijas
Published: March 2021

Background

Severe acute respiratory syndrome virus 2 (SARS-CoV-2) is spreading globally and causes most frequently fever and respiratory symptoms, i.e. Coronavirus disease 2019 (COVID-19), however, distinct neurological syndromes associated with SARS-CoV-2 infection have been described. Among SARS-CoV-2-infections-associated neurological symptoms fatigue, headache, dizziness, impaired consciousness and anosmia/ageusia are most frequent, but less frequent neurological deficits such as seizures, Guillain-Barré syndrome or ataxia may also occur.

Case presentation

Herein we present a case of a 62-year-old man who developed a subacute cerebellar syndrome with limb-, truncal- and gait ataxia and scanning speech 1 day after clinical resolution of symptomatic SARS-CoV-2 infection of the upper airways. Apart from ataxia, there were no signs indicative of opsoclonus myoclonus ataxia syndrome or Miller Fisher syndrome. Cerebral magnetic resonance imaging showed mild cerebellar atrophy. SARS-CoV-2 infection of the cerebellum was excluded by normal cerebrospinal fluid cell counts and, most importantly, absence of SARS-CoV-2 RNA or intrathecal SARS-CoV-2-specific antibody production. Other causes of ataxia such as other viral infections, other autoimmune and/or paraneoplastic diseases or intoxication were ruled out. The neurological deficits improved rapidly after high-dose methylprednisolone therapy.

Conclusions

The laboratory and clinical findings as well as the marked improvement after high-dose methylprednisolone therapy suggest a post-infectious, immune-mediated cause of ataxia. This report should make clinicians aware to consider SARS-CoV-2 infection as a potential cause of post-infectious neurological deficits with an atypical clinical presentation and to consider high-dose corticosteroid treatment in case that a post-infectious immune-mediated mechanism is assumed.
The effectiveness of the laid-back position on lactation-related nipple problems and comfort: a meta-analysis
Authors: Wang Zhi , Liu Qiuyue , Min Lihua , Mao Xiaorong
Published: March 2021

Background

The importance of breastfeeding for maternal and child health is agreed upon worldwide. However, lactation-related nipple problems are common and are important factors affecting breastfeeding. Multiple studies recommended laid-back breastfeeding, but they are of various levels of quality, and the results are inconclusive.

Methods

We systematically searched the following twelve databases from inception to January 28,2020: Cochrane Library, EMBASE, Medline, Ovid, PubMed, Web of Science, CINAHL, Scopus, Chinese National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), WanFang, and VIP. All studies regarding laid-back breastfeeding or biological nurturing were considered, regardless of whether they were randomized controlled trials. Two trained investigators independently evaluated the quality of the selected articles and screened the data. All the data were analysed separately using Review Manager Version 5.3 and STATA/SE Version 15.1.

Results

A total of 12 studies involving 1936 groups of postpartum women and their newborns were included. The results of the meta-analysis showed that nipple pain (RR = 0.24; 95% CI 0.14, 0.40;p < 0.00001), nipple trauma (RR = 0.47; 95% CI 0.29, 0.75;p = 0.002) and correct latching position (RR = 1.22; 95% CI 1.11, 1.33;p < 0.0001) in the experimental groups were all better than those of the control groups, and the differences were statistically significant (p < 0.05), which indicates that the laid-back position has a positive effect on maternal breastfeeding. However, the results of position comfort showed that there was no statistical significance between the two groups (ES = 0.09; 95% CI -0.63, 0.81;p = 0.798).

Conclusion

Compared with traditional breastfeeding positions, the laid-back position has been proven to be related to a decreased incidence of nipple pain and nipple trauma and is seemingly conducive to the use of the correct latching position. It is suggested that the laid-back position is helpful in solving lactation-related nipple problems and can be recommended as a position for breastfeeding. However, no significant difference in position comfort was found between the two groups based on the current evidence, and further studies are still needed to validate these results due to the limitations of the included studies.
Impact of gestational diabetes mellitus diagnosed during the third trimester on pregnancy outcomes: a case-control study
Authors: Shindo Ryosuke , Aoki Shigeru , Nakanishi Sayuri , Misumi Toshihiro , Miyagi Etsuko
Published: March 2021

Background

In 2010, the International Association of Diabetes and Pregnancy Study Group (IADPSG) proposed new criteria indicating that gestational diabetes mellitus (GDM) can be diagnosed if the fasting threshold of ≤92 mg/dL, 1-h threshold of ≤180 mg/dL, or 2-h threshold of ≤153 mg/dL are exceeded during the 75-g 2-h oral glucose tolerance test (OGTT) performed at 24–28 weeks of gestation. The World Health Organization (WHO) recommends using the proposed diagnostic threshold values of the IADPSG to diagnose GDM; however, it does not limit the timing of the 75-g OGTT. Since 2010 in Japan, GDM has been diagnosed using the same criteria as that proposed by the WHO. However, neither the JSOG nor the WHO has provided any evidence that it is appropriate to use a threshold beyond the range recommended by the IADPSG.

Methods

This was a single-centre retrospective study based on the medical records and delivery registry database of our centre. We included women who underwent a 50-g glucose challenge test (GCT) with results < 140 mg/dL at 24–28 weeks of gestation and subsequently underwent a 75-g OGTT after 29 weeks of gestation with abnormal glucose tolerance suspected based on clinical findings. The reference values for the 75-g OGTT followed the IADPSG criteria. Subjects were classified into the normal glucose tolerance (NGT) group and the GDM group. The type of delivery and neonatal outcomes of the two groups were compared. A multivariable analysis was performed to match the backgrounds of both groups.

Results

In total, the NGT and GDM group comprised 189 and 49 women, respectively. Emergency caesarean delivery rates were similar in the GDM and NGT groups (10.6 and 12.2%, respectively; adjusted odds ratio [OR], 1.25; 95% confidence interval [CI], 0.43–3.64; p = 0.74); however, the elective caesarean delivery rate was higher in the GDM group than in the NGT group (16.3 and 5.3%, respectively, adjusted OR, 3.60; 95% CI, 1.27–10.19; p = 0.01). No significant differences were observed in other maternal and neonatal outcomes between both groups.

Conclusion

Although a diagnosis of GDM during the third trimester does not improve pregnancy outcomes, it increases the elective caesarean delivery rate.
FOXD1 regulates cell division in clear cell renal cell carcinoma
Authors: Bond Kyle H. , Fetting Jennifer L. , Lary Christine W. , Emery Ivette F. , Oxburgh Leif
Published: March 2021

Background

Forkhead transcription factors control cell growth in multiple cancer types.Foxd1is essential for kidney development and mitochondrial metabolism, but its significance in renal cell carcinoma (ccRCC) has not been reported.

Methods

Transcriptome data from the TCGA database was used to correlateFOXD1expression with patient survival.FOXD1was knocked out in the 786-O cell line and known targets were analyzed. Reduced cell growth was observed and investigated in vitro using growth rate and Seahorse XF metabolic assays and in vivo using a xenograft model. Cell cycle characteristics were determined by flow cytometry and immunoblotting. Immunostaining for TUNEL and γH2AX was used to measure DNA damage. Association of theFOXD1pathway with cell cycle progression was investigated through correlation analysis using the TCGA database.

Results

FOXD1expression level in ccRCC correlated inversely with patient survival. Knockout ofFOXD1in 786-O cells altered expression of FOXD1 targets, particularly genes involved in metabolism (MICU1) and cell cycle progression. Investigation of metabolic state revealed significant alterations in mitochondrial metabolism and glycolysis, but no net change in energy production. In vitro growth rate assays showed a significant reduction in growth of 786-OFOXD1null. In vivo, xenografted 786-OFOXD1nullshowed reduced capacity for tumor formation and reduced tumor size. Cell cycle analysis showed that 786-OFOXD1nullhad an extended G2/M phase. Investigation of mitosis revealed a deficiency in phosphorylation of histone H3 in 786-OFOXD1null, and increased DNA damage. Genes correlate withFOXD1in the TCGA dataset associate with several aspects of mitosis, including histone H3 phosphorylation.

Conclusions

We show that FOXD1 regulates the cell cycle in ccRCC cells by control of histone H3 phosphorylation, and that FOXD1 expression governs tumor formation and tumor growth. Transcriptome analysis supports this role for FOXD1 in ccRCC patient tumors and provides an explanation for the inverse correlation between tumor expression ofFOXD1and patient survival. Our findings reveal an important role for FOXD1 in maintaining chromatin stability and promoting cell cycle progression and provide a new tool with which to study the biology of FOXD1 in ccRCC.
Detection of tumor-derived extracellular vesicles in plasma from patients with solid cancer
Authors: Vitale Silvia R. , Helmijr Jean A. , Gerritsen Marjolein , Coban Hicret , van Dessel Lisanne F. , Beije Nick , van der Vlugt-Daane Michelle , Vigneri Paolo , Sieuwerts Anieta M. , Dits Natasja , van Royen Martin E. , Jenster Guido , Sleijfer Stefan , Lolkema Martijn , Martens John W. M. , Jansen Maurice P. H. M.
Published: March 2021

Background

Extracellular vesicles (EVs) are actively secreted by cells into body fluids and contain nucleic acids of the cells they originate from. The goal of this study was to detect circulating tumor-derived EVs (ctEVs) by mutant mRNA transcripts (EV-RNA) in plasma of patients with solid cancers and compare the occurrence of ctEVs with circulating tumor DNA (ctDNA) in cell-free DNA (cfDNA).

Methods

For this purpose, blood from 20 patients and 15 healthy blood donors (HBDs) was collected in different preservation tubes (EDTA, BCT, CellSave) and processed into plasma within 24 h from venipuncture. EVs were isolated with the ExoEasy protocol from this plasma and from conditioned medium of 6 cancer cell lines and characterized according to MISEV2018-guidelines. RNA from EVs was isolated with the ExoRNeasy protocol and evaluated for transcript expression levels of 96 genes by RT-qPCR and genotyped by digital PCR.

Results

Our workflow applied on cell lines revealed a high concordance between cellular mRNA and EV-RNA in expression levels as well as variant allele frequencies for PIK3CA, KRAS and BRAF. Plasma CD9-positive EV and GAPDH EV-RNA levels were significantly different between the preservation tubes. The workflow detected only ctEVs with mutant transcripts in plasma of patients with high amounts (> 20%) of circulating tumor DNA (ctDNA). Expression profiling showed that the EVs from patients resemble healthy donors more than tumor cell lines supporting that most EVs are derived from healthy tissue.

Conclusions

We provide a workflow for ctEV detection by spin column-based generic isolation of EVs and PCR-based measurement of gene expression and mutant transcripts in EV-RNA derived from cancer patients’ blood plasma. This workflow, however, detected tumor-specific mutations in blood less often in EV-RNA than in cfDNA.
Do work ability and life satisfaction matter for return to work? Predictive ability of the work ability index and life satisfaction questionnaire among women with long-term musculoskeletal pain
Authors: Rashid Mamunur , Heiden Marina , Nilsson Annika , Kristofferzon Marja-Leena
Published: March 2021

Background

Impaired work ability and reduced life satisfaction due to long-term musculoskeletal pain, particularly in neck, shoulders and back, are considered occupational health problems that can result in workers taking sick leave. The aim of the study was to determine whether work ability and life satisfaction predict return to work (RTW) among women with long-term neck/shoulder and/or back pain, and to assess the ability of the Work Ability Index (WAI) and the Life Satisfaction Questionnaire (LiSat-11) to discriminate between those who did RTW and those who did not RTW (NRTW).

Methods

This is a cohort study with 1-year follow-up. A survey was sent to 600 women receiving sick leave benefits from the Swedish Social Insurance Agency. In total, 208 women responded at baseline, and 141 at a 1-year follow-up. To identify whether work ability and life satisfaction predicted RTW, multiple logistic regression analyses were performed with and without adjustment for type of work and pain intensity. To assess the discriminative ability of the WAI and the LiSat-11 for women who did RTW and those who did NRTW, receiver operating characteristic curves were fitted.

Results

Work ability predicted RTW, and the results remained significant after adjusting for type of work and pain intensity (OR 1.12, 95% CI: 1.04–1.22). Life satisfaction was not significant. The WAI at baseline adequately discriminated between RTW and NRTW after 1 year (Area under curve 0.78, 95% CI: 0.70–0.86), but the LiSat-11 did not.

Conclusions

This study supports a relationship between work ability and RTW among women on sick leave for long-term neck/shoulder and/or back pain. The results indicate that the WAI, but not the LiSat-11, can discriminate between RTW and NRTW in the population under study. Although the discriminative ability of the WAI needs to be verified in new samples before it can be recommended for use in rehabilitation settings, we suggest that healthcare professionals consider how women perceive their work ability in order to better support them in their RTW.
Deep learning diagnostic and risk-stratification pattern detection for COVID-19 in digital lung auscultations: clinical protocol for a case–control and prospective cohort study
Authors: Glangetas Alban , Hartley Mary-Anne , Cantais Aymeric , Courvoisier Delphine S. , Rivollet David , Shama Deeksha M. , Perez Alexandre , Spechbach Hervé , Trombert Véronique , Bourquin Stéphane , Jaggi Martin , Barazzone-Argiroffo Constance , Gervaix Alain , Siebert Johan N.
Published: March 2021

Background

Lung auscultation is fundamental to the clinical diagnosis of respiratory disease. However, auscultation is a subjective practice and interpretations vary widely between users. The digitization of auscultation acquisition and interpretation is a particularly promising strategy for diagnosing and monitoring infectious diseases such as Coronavirus-19 disease (COVID-19) where automated analyses could help decentralise care and better inform decision-making in telemedicine. This protocol describes the standardised collection of lung auscultations in COVID-19 triage sites and a deep learning approach to diagnostic and prognostic modelling for future incorporation into an intelligent autonomous stethoscope benchmarked against human expert interpretation.

Methods

A total of 1000 consecutive, patients aged ≥ 16 years and meeting COVID-19 testing criteria will be recruited at screening sites and amongst inpatients of the internal medicine department at the Geneva University Hospitals, starting from October 2020. COVID-19 is diagnosed by RT-PCR on a nasopharyngeal swab and COVID-positive patients are followed up until outcome (i.e., discharge, hospitalisation, intubation and/or death). At inclusion, demographic and clinical data are collected, such as age, sex, medical history, and signs and symptoms of the current episode. Additionally, lung auscultation will be recorded with a digital stethoscope at 6 thoracic sites in each patient. A deep learning algorithm (DeepBreath) using a Convolutional Neural Network (CNN) and Support Vector Machine classifier will be trained on these audio recordings to derive an automated prediction of diagnostic (COVID positive vs negative) and risk stratification categories (mild to severe). The performance of this model will be compared to a human prediction baseline on a random subset of lung sounds, where blinded physicians are asked to classify the audios into the same categories.

Discussion

This approach has broad potential to standardise the evaluation of lung auscultation in COVID-19 at various levels of healthcare, especially in the context of decentralised triage and monitoring.

Trial registration: PB_2016-00500, SwissEthics. Registered on 6 April 2020.
An acquired plica-induced notch in the medial femoral condyle in a patient with medial patellar plica syndrome: a case report
Authors: Kim Sung-Jae , Koh Yong Gon , Kim Yong Sang
Published: March 2021

Background

An inflamed and thickened medial patellar plica (MPP) caused by repeated mechanical irritation from trauma or overuse leads to impingement between the anterior medial femoral condyle and the medial articular facet of the patella and produces pain or clicking, which is known as MPP syndrome. In patients with MPP syndrome, cartilage damage may occur depending on the shape of the MPP and the duration of the impingement.

Case presentation

Preoperative magnetic resonance imaging in a 17-year-old male patient with MPP syndrome showed a hypertrophic MPP along with an abnormal notch in the articular surface of the medial femoral condyle. We considered that the impinged hypertrophic plica between the anterior medial femoral condyle and the medial articular facet of the patella resulted in cartilage damage on the articular surface of the medial femoral condyle. However, during arthroscopic surgery, we found that the cartilage of the notch, which was located beneath the MPP, was completely intact. We concluded that this abnormal notch had developed gradually in the MPP without cartilage damage.

Conclusions

Surgeons should be mindful that acquired plica-induced notches in the articular surface of the medial femoral condyle can present in patients with MPP syndrome.
Work environment, job satisfaction and burnout among Spanish dentists: a cross-sectional study
Authors: Molina-Hernández Javier , Fernández-Estevan Lucía , Montero Javier , González-García Lorena
Published: March 2021

Background

The main aim of the present study was to examine the relationships among work environment, job satisfaction and burnout in dentists and to analyse the way in which certain sociodemographic variables, such as gender, professional experience and weekly working hours, predict the perception of the work environment.

Methods

A battery of online questionnaires was sent to 3876 dentists officially registered in the triple-province region of Valencia; the battery included the Survey of Organizational Attributes for Dental Care, the Warr–Cook–Wall Overall Job Satisfaction Scale, the Maslach Burnout Inventory and a series of sociodemographic questions formulated for the specific purpose of this study. To assess the relations with the independent variables, we calculated the Pearson correlation coefficient, the Z-scores were calculated to make effect sizes comparable, and the associations between the scales and the sociodemographic variables were investigated by adjusted multiple regression analysis.

Results

A total of 336 participants (9.4%) correctly completed the survey in this study. The mean (M) age was 37.6 years old (standard deviation (SD) = 9.6, median (Me) = 34). Participants reported high scores on the work environment and job satisfaction scales, with only limited experiences of burnout (3.8%). Work environment and burnout were significantly and positively predicted by years of professional experience (β = .078; p = .000 and β = .107; p = .004, respectively), and job satisfaction was significantly and positively predicted by weekly hours of work (β = .022; p = .001), without significant differences according to gender.

Conclusions

Dentists who work over 20 hours a week and have more years of professional experience report having better perceptions of well-being at work, with no significant difference according to gender. It is important to highlight the aspects that improve well-being in dentistry to reduce burnout, which would lead to greater work engagement and better attention to patients.
Perceived general health in relation to oral health status in a rural Kenyan elderly population
Authors: Fukuda Hideki , Hayashi Yoshihiko , Toda Kazuo , Kaneko Satoshi , Wagaiyu Evelyn
Published: March 2021

Background

This study aimed to determine the present oral health status of the rural Kenyan elderly population and to investigate whether oral health status is associated with the perceived general health.

Methods

A total of 131 individuals aged 65 years and over in Mbita Constituency, Homa Bay County in Kenya were randomly selected and visited at home. The home visit study, which was conducted from 2014 to 2016, included oral examination by a dentist and administration of a self-reporting questionnaire. The number of teeth present and functional tooth unit (FTU) points were calculated using the dental chart. Perceived general health, subjective masticatory ability, and self-reported periodontal symptoms were collected using a questionnaire sheet. Fisher’s exact test and nonparametric test were used to determine the difference in percentage and means. The odds ratio of good general health based on the participants’ masticatory satisfaction was calculated by logistic analysis.

Results

Satisfactory mastication was dependent on the number of teeth present, FTU points, and self-reported “gum bleeding” and “tooth mobility”. Furthermore, satisfactory mastication was associated with perceived general health status independent of sex and age. The adjusted odds ratio of good perceived general health was 2.29 (95% confidence interval 1.05–4.99) for participants who had the subjective masticatory ability.

Conclusion

Among the Kenyan elderly population, satisfactory mastication was related to the number of teeth present, FTU points, and self-reported periodontal symptoms. Furthermore, satisfactory mastication was associated with perceived general health status independently.