bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanopore guided annotation of transcriptome architectures
Authors: Abebe Jonathan S. , Alwie Yasmine , Fuhrmann Erik , Leins Jonas , Mai Julia , Verstraten Ruth , Schreiner Sabrina , Wilson Angus C. , Depledge Daniel P. 
Published: July 2024

ABSTRACT

Nanopore direct RNA sequencing (DRS) enables the capture and full-length sequencing of native RNAs, without recoding or amplification bias. Resulting data sets may be interrogated to define the identity and location of chemically modified ribonucleotides, as well as the length of poly(A) tails, on individual RNA molecules. The success of these analyses is highly dependent on the provision of high-resolution transcriptome annotations in combination with workflows that minimize misalignments and other analysis artifacts. Existing software solutions for generating high-resolution transcriptome annotations are poorly suited to small gene-dense genomes of viruses due to the challenge of identifying distinct transcript isoforms where alternative splicing and overlapping RNAs are prevalent. To resolve this, we identified key characteristics of DRS data sets that inform resulting read alignments and developed the nanopore guided annotation of transcriptome architectures (NAGATA) software package (
https://github.com/DepledgeLab/NAGATA
). We demonstrate, using a combination of synthetic and original DRS data sets derived from adenoviruses, herpesviruses, coronaviruses, and human cells, that NAGATA outperforms existing transcriptome annotation software and yields a consistently high level of precision and recall when reconstructing both gene sparse and gene-dense transcriptomes. Finally, we apply NAGATA to generate the first high-resolution transcriptome annotation of the neglected pathogen human adenovirus type F41 (HAdV-41) for which we identify 77 distinct transcripts encoding at least 23 different proteins.

IMPORTANCE
The transcriptome of an organism denotes the full repertoire of encoded RNAs that may be expressed. This is critical to understanding the biology of an organism and for accurate transcriptomic and epitranscriptomic-based analyses. Annotating transcriptomes remains a complex task, particularly in small gene-dense organisms such as viruses which maximize their coding capacity through overlapping RNAs. To resolve this, we have developed a new software nanopore guided annotation of transcriptome architectures (NAGATA) which utilizes nanopore direct RNA sequencing (DRS) datasets to rapidly produce high-resolution transcriptome annotations for diverse viruses and other organisms.
Involvement of 2-deoxyglucose-6-phosphate phosphatases in facilitating resilience against ionic and osmotic stress in
Saccharomyces cerevisiae
Authors: Awasthy Chinmayee , Hefny Zeinab Abdelmoghis , Van Genechten Wouter , Himmelreich Uwe , Van Dijck Patrick 
Published: July 2024

ABSTRACT

The
Saccharomyces cerevisiae DOG
genes,
DOG1
and
DOG2
, encode for 2-deoxyglucose-6-phosphate phosphatases. These enzymes of the haloacid dehalogenase superfamily are known to utilize the non-natural 2-deoxyglucose-6-phosphate as their substrate. However, their physiological substrate and hence their biological role remain elusive. In this study, we investigated their potential role as enzymes in biosynthesizing glycerol through an alternative pathway, which involves the dephosphorylation of dihydroxyacetone phosphate into dihydroxyacetone, as opposed to the classical pathway which utilizes glycerol 3-phosphate. Overexpression of
DOG1
or
DOG2
rescued the osmotic and ionic stress-sensitive phenotype of
gpp1∆ gpp2∆
or
gpd1∆ gpd2∆
mutants, both affected in the production of glycerol. While small amounts of glycerol were observed in the
DOG
overexpression strains in the
gpp1∆ gpp2∆
background, no glycerol was detected in the
gpd1∆ gpd2∆
mutant background. This indicates that overexpression of the
DOG
enzymes can rescue the osmosensitive phenotype of the
gpd1∆ gpd2∆
mutant independent of glycerol production. We also did not observe a drop in glycerol levels in the
gpp1∆ gpp2∆ dog1∆ dog2∆
as compared to the
gpp1∆ gpp2∆
mutant, indicating that the Dog enzymes are not involved in glycerol biosynthesis. This indicates that Dog enzymes have a distinct substrate and their function within the cell remains undiscovered.

IMPORTANCE

Yeast stress tolerance is an important characteristic that is studied widely, not only regarding its fundamental insights but also for its applications within the biotechnological industry. Here, we investigated the function of two phosphatase encoding genes,
DOG1
and
DOG2
, which are induced as part of the general stress response pathway, but their natural substrate in the cells remains unclear. They are known to dephosphorylate the non-natural substrate 2-deoxyglucose-6-phosphate. Here, we show that overexpression of these genes overcomes the osmosensitive phenotype of mutants that are unable to produce glycerol. However, in these overexpression strains, very little glycerol is produced indicating that the Dog enzymes do not seem to be involved in a previously predicted alternative pathway for glycerol production. Our work shows that overexpression of the DOG genes may improve osmotic and ionic stress tolerance in yeast.
Commonalities and differences in injured patient experiences of accessing and receiving quality injury care: a qualitative study in three sub-Saharan African countries
Authors: Kennedy Ciaran , Ignatowicz Agnieszka , Odland Maria Lisa , Abdul-Latif Abdul-Malik , Belli Antonio , Howard Anthony , Whitaker John , Chu Kathryn M , Ferreira Karen , Owolabi Eyitayo O , Nyamathe Samukelisiwe , Tabiri Stephen , Ofori Bernard , Pognaa Kunfah Sheba Mary , Yakubu Mustapha , Bekele Abebe , Alyande Barnabas , Nzasabimana Pascal , Byiringiro Jean-Claude , Davies Justine 
Published: July 2024

ObjectivesTo understand commonalities and differences in injured patient experiences of accessing and receiving quality injury care across three lower-income and middle-income countries.DesignA qualitative interview study. The interviews were audiorecorded, transcribed and thematically analysed.SettingUrban and rural settings in Ghana, South Africa and Rwanda.Participants59 patients with musculoskeletal injuries.ResultsWe found five common barriers and six common facilitators to injured patient experiences of accessing and receiving high-quality injury care. The barriers encompassed issues such as service and treatment availability, transportation challenges, apathetic care, individual financial scarcity and inadequate health insurance coverage, alongside low health literacy and information provision. Facilitators included effective information giving and informed consent practices, access to health insurance, improved health literacy, empathetic and responsive care, comprehensive multidisciplinary management and discharge planning, as well as both informal and formal transportation options including ambulance services. These barriers and facilitators were prevalent and shared across at least two countries but demonstrated intercountry and intracountry (between urbanity and rurality) variation in thematic frequency.ConclusionThere are universal factors influencing patient experiences of accessing and receiving care, independent of the context or healthcare system. It is important to recognise and understand these barriers and facilitators to inform policy decisions and develop transferable interventions aimed at enhancing the quality of injury care in sub-Saharan African nations.
Untangling the relationships between age, gender, type of sport, perfectionistic self-presentation and motivation on body satisfaction: a cross-sectional study on aesthetic and non-aesthetic female and male athletes aged 10 to 22 years
Authors: Lundqvist Carolina , Kolbeinsson Örn , Asratian Anna , Wade Tracey D 
Published: July 2024

ObjectivesTo explore the relationships between age, gender, type of sport, perfectionistic self-presentation and motivation on body satisfaction among young athletes in one aesthetic sport (gymnastics) and one non-aesthetic sport (basketball). The study hypothesise that (1) age, gender and type of sport (aesthetic or non-aesthetic) will predict body satisfaction scores, (2) autonomous motivation will positively be related to body satisfaction and (3) perfectionistic self-presentation will negatively be related to body satisfaction.DesignCross-sectional.Method209 athletes (132 gymnasts and 77 basketball players) aged 10–22 (median=13) years were recruited. After data screening, 200 athletes were included in analyses (females: n=155; males: n=45). Participants completed an online survey, which assessed demographic information, athlete motivation (Behavioural Regulation in Sport Questionnaire), perfectionistic self-presentation (Perfectionistic Self-Presentation Scale—Junior Form) and body satisfaction (Body Appreciation Scale-2).ResultsHierarchical multiple regression showed age, self-assigned gender, and two facets of perfectionistic self-presentation (ie, perfectionistic presentation and non-disclosure of imperfection) to predict reported levels of body satisfaction significantly. Subsequently, adding motivational variables did not improve the model. A moderation analysis showed that the relationship between non-disclosure of imperfection and body satisfaction was significantly moderated by gender.ConclusionsTwo facets of perfectionistic self-presentation were associated with reported body satisfaction. Additionally, the relationship between non-disclosure of imperfection and body satisfaction appears to differ between female and male athletes. Researchers should move beyond sport types and identify factors (eg, perfectionistic self-presentation) at the individual and environmental levels that can protect young athletes’ body satisfaction.
Measuring the impact of specific surgical complications after ovarian cancer cytoreductive surgery on short-term outcomes
Authors: Mohammad Arwa , Ainio Chiara , Narasimhulu Deepa Maheswari , McGree Michaela , Weaver Amy L , Kumar Amanika , Garbi Annalisa , Mariani Andrea , Aletti Giovanni , Multinu Francesco , Langstraat Carrie , Cliby William 
Published: July 2024

Objective
We sought to measure the impact of specific peri-operative complications after primary cytoreductive surgery on relevant patient outcomes and use of resources.

Methods
A cohort of patients with advanced ovarian cancer who underwent primary cytoreductive surgery at two institutions (2006–2016) were studied. Specific known complications (‘exposures’) within 30 days of surgery were evaluated to determine the impact on outcomes. Exposures included bowel leak, superficial surgical site infection, deep surgical site infection, venous thromboembolic event, and cardiac event. Outcomes were prolonged lengths of stay, readmission or non-home discharge, reoperation, organ failure, delay to adjuvant chemotherapy, and 90-day mortality. Population attributable risk (PAR) was used to estimate the proportion of adverse outcomes that could be prevented by elimination of a causal exposure and considers both the strength of the association and the prevalence of the complication; adjusted PARs (aPAR) were calculated using adjusted relative risks (aRR) adjusted for stage (IIIC vs IV) and American Society of Anesthesiology score (<3 vs ≥3).

Results
A cohort of 892 patients was included. Each of the evaluated exposures had an impact on readmission/non-home discharge (aPAR range 5.3 to 13.5). A venous thromboembolic event was significantly associated with 90-day mortality (aRR=2.9 (95% CI 1.3 to 6.7); aPAR=8.6 (95% CI −1.8 to 19.1)) and organ failure (aRR=4.7 (95% CI 2.3 to 9.5); aPAR=13.9 (95% CI 2.8 to 25.1)). Similarly, a cardiac event was most strongly associated with organ failure and was very impactful (aPAR=19.0 (95% CI 6.8 to 31.1)).
Bowel leak was a major contributor to poor outcome, including reoperation (aPAR=45.5 (95% CI 34.3 to 56.6)), organ failure (aPAR=13.6 (95% CI 2.6 to 24.6)), readmission/non-home discharge (aPAR=5.3 (95% CI 1.6 to 9.0)), delay to adjuvant chemotherapy (aPAR=5.9 (95% CI 2.3 to 9.4)), and prolonged lengths of stay (aPAR=13.0 (95% CI 9.1 to 16.9)).

Conclusion
Going beyond reporting complications using common scales to measure their genuine impact provides important information for providers, patients, and payers. We report that less frequent exposures, including a venous thromboembolic event, cardiac events, and bowel leaks, have a high impact on patients and use of resources.
Molecular classification of endometrial carcinoma on endometrial biopsy: an early prognostic value to guide personalized treatment
Authors: Restaino Stefano , Poli Alice , Arcieri Martina , Mariuzzi Laura , Orsaria Maria , Tulisso Angelica , Pellecchia Giulia , Paparcura Federico , Petrillo Marco , Bogani Giorgio , Cianci Stefano , Capozzi Vito Andrea , Biasioli Anna , Buda Alessandro , Mauro Jessica , Fanfani Francesco , Fagotti Anna , Driul Lorenza , Scambia Giovanni , Vizzielli Giuseppe 
Published: July 2024

Objective
Molecular features are essential for estimating the risk of recurrence and impacting overall survival in patients with endometrial cancer. Additionally, the surgical procedure itself could be personalized based on the molecular characteristics of the tumor. This study aims to assess the feasibility of obtaining reliable molecular classification status from biopsy specimens collected during hysteroscopy to better modulate the appropriate surgical treatment.

Methods
This monocentric, retrospective, observational study was conducted on 106 patients who underwent a biopsy procedure followed by radical surgery for endometrial cancer, with concurrent molecular investigation. The molecular classification was determined through immunohistochemical staining for p53 and mismatch repair proteins, along with gene sequencing for POLE.

Results
Overall, 106 patients underwent molecular investigation, which was finally achieved on 99 patients (93.4%). Among these, the molecular analysis was conducted in 71 patients (67%) on the pre-operative endometrial biopsy and on the final uterine specimen in 28 patients (26.4%). Most of the endometrial biopsies were performed using Bettocchi hysteroscopy (66%). Molecular analysis was not possible in seven patients (6.6%), with six cases due to sample inadequacy and one case attributed to intra-mucosal carcinoma. The molecular results showed that the copy number low sub-group was the most common, and five cases of ‘multiple classifiers’ were observed in the low-risk category.

Conclusion
Our experience in obtaining molecular information from biopsy samples underscores the feasibility and efficacy of this technique, even in small tissue samples. This capability helps define the prognostic group of patients, facilitates timely decision-making, and develops a personalized strategy for each patient.
Use of social media for academic and professional purposes by gynecologic oncologists
Authors: Bhandoria Geetu Prakash , Jayraj Aarthi S , Tiwari Shyamji , Migliorelli Federico , Nelson Gregg , van Ramshorst Gabriëlle H , Kacperczyk-Bartnik Joanna , Angeles Martina Aida , Nair Navya , El Hajj Houssein , Bizzarri Nicolò 
Published: July 2024

ObjectiveTo investigate the prevalence and patterns of social media use among gynecologic oncologists for professional and academic purposes.MethodsA prospective online survey between November and December 2022 targeted gynecologic oncology practitioners (gynecologic oncologists, surgical oncologists, medical oncologists, radiation/clinical oncologists, and onco-pathologists/pathologists). The survey, distributed via various social media platforms, included 40 questions to capture qualitative and quantitative data on social media use.ResultsOf 131 respondents from 32 countries, 106 (80.9%) were gynecologic oncologists and affiliated with academic institutions (84.7%). Facebook (n=110, 83.9%), Twitter (n= 108, 82.4%), and Instagram (n=100, 76.3%) were the most used platforms. Respondents used social media to stay updated (n=101, 77.1%), network (n=97, 74%), learn about conferences and webinars (n=97, 74%), and engage in academic discussions (n=84, 64.1%). Following the COVID-19 pandemic, 100/129 (77.5%) reported increased social media use. However, only 32 (24.4%) used it to connect with patients, and concerns were raised about privacy and the need for separate professional and personal accounts. A quarter of respondents hesitated to share their opinions on social media due to the fear of controversy, with 26 (20%) experiencing cyberbullying, yet 120/130 (92.3%) believed it enabled junior professionals to express their views. Concerns about differentiating valid content, information reliability, and the professional perception of sourcing knowledge from social media were noted. Gender, age, specialty, and income level influenced patterns of social media use, with variations in preferences for platforms, content engagement, and purposes, highlighting a complex landscape of social media interaction among gynecologic oncologists.ConclusionWhile the use of social media among gynecologic oncologists is prevalent, particularly for academic and professional development, challenges such as cyberbullying, privacy concerns, and the need for formal training in social media navigation persist. Tailored training programs and guidelines could enhance social media’s effective and ethical use in this field, promoting a safe environment for professional expression and engagement.
Extensive-stage small-cell lung cancer in patients receiving atezolizumab plus carboplatin–etoposide: stratification of outcome based on a composite score that combines gene expression profiling and immune characterization of microenvironment
Authors: Tosi Anna , Lorenzi Martina , Del Bianco Paola , Roma Anna , Pavan Alberto , Scapinello Antonio , Resi Maria Vittoria , Bonanno Laura , Frega Stefano , Calabrese Fiorella , Guarneri Valentina , Rosato Antonio , Pasello Giulia 
Published: July 2024

PurposeSmall-cell lung cancer (SCLC) is an aggressive disease with a dismal prognosis. The addition of immune checkpoints inhibitors to standard platinum-based chemotherapy in first-line setting achieves a durable benefit only in a patient subgroup. Thus, the identification of predictive biomarkers is an urgent unmet medical need.Experimental designTumor samples from naive extensive-stage (ES) SCLC patients receiving atezolizumab plus carboplatin–etoposide were analyzed by gene expression profiling and two 9-color multiplex immunofluorescence panels, to characterize the immune infiltrate and SCLC subtypes. Associations of tissue biomarkers with time-to-treatment failure (TTF), progression-free survival (PFS) and overall survival (OS), were assessed.Results42 patients were included. Higher expression of exhausted CD8-related genes was independently associated with a longer TTF and PFS while increased density of B lymphocytes correlated with longer TTF and OS. Higher percentage of M2-like macrophages close to tumor cells and of CD8+T cells close to CD4+T lymphocytes correlated with increased risk of TF and longer survival, respectively. A lower risk of TF, disease progression and death was associated with a higher density of ASCL1+tumor cells while the expression of POU2F3 correlated with a shorter survival. A composite score combining the expression of exhausted CD8-related genes, B lymphocyte density, ASCL1 tumor expression and quantification of CD163+macrophages close to tumor cells, was able to stratify patients into high-risk and low-risk groups.ConclusionsIn conclusion, we identified tissue biomarkers and a combined score that can predict a higher benefit from chemoimmunotherapy in ES-SCLC patients.
Intercurrent infection as a risk factor for disease flares in patients with systemic lupus erythematosus
Authors: el Hadiyen Fatma , Tsang-A-Sjoe Michel W P , Lissenberg-Witte Birgit I , Voskuyl Alexandre E , Bultink Irene E M 
Published: July 2024

ObjectiveTo determine whether intercurrent infections are a risk factor for subsequent disease flares in systemic lupus erythematosus (SLE).MethodsDemographic and clinical characteristics of 203 patients with SLE participating in the Amsterdam SLE cohort were collected at baseline and during follow-up. Collection of data on infections and SLE flares was registry-based and infections and flares were categorised as minor or major, based on predefined criteria. Proportional hazard models with recurrent events and time-varying covariates were used to estimate the HR of SLE flares.ResultsThe incidence rates of major and minor infections were 5.3 per 100 patient years and 63.9 per 100 patient years, respectively. The incidence rates of flares were 3.6 and 15.1 per 100 patient years for major flares and minor flares, respectively.In the proportional hazard model, intercurrent infections (major and minor combined) were associated with the occurrence of SLE flares (major and minor combined; HR 1.9, 95% CI: 1.3 to 2.9). The hazard ratio for a major SLE flare following a major infection was 7.4 (95% CI: 2.2 to 24.6). Major infections were not associated with the occurrence of minor flares.ConclusionsThe results of the present study show that intercurrent infections are associated with subsequent SLE flares, which supports the hypothesis that infections may trigger SLE flares.
Exposure to fibres and risk of pleural mesothelioma in the Norwegian Offshore Petroleum Workers cohort
Authors: Berge Leon Alexander Mclaren , Shala Nita Kaupang , Barone-Adesi Francesco , Hosgood H Dean , Samuelsen Sven Ove , Bråtveit Magne , Kirkeleit Jorunn , Silverman Debra , Friesen Melissa C , Babigumira Ronnie , Grimsrud Tom K , Veierød Marit B , Stenehjem Jo S 
Published: July 2024

ObjectivesPleural mesothelioma is a rare respiratory cancer, mainly caused by inhalation of asbestos fibres. Other inorganic fibres are also suggested risk factors. We aimed to investigate the association between exposure to asbestos or refractory ceramic fibres (RCFs) and pleural mesothelioma among male Norwegian offshore petroleum workers.MethodsAmong 25 347 men in the Norwegian Offshore Petroleum Workers (NOPW) cohort (1965–1998), 43 pleural mesothelioma cases were identified through the Cancer Registry of Norway (1999–2022). A case–cohort study was conducted with 2095 randomly drawn non-cases from the cohort. Asbestos and RCF exposures were assessed with expert-made job-exposure matrices (JEMs). Weighted Cox regression was used to estimate HRs and 95% CIs, adjusted for age at baseline and pre-offshore employment with likely asbestos exposure.ResultsAn increased risk of pleural mesothelioma was indicated for the highest versus lowest tertile of average intensity of asbestos (HR=1.21, 95% CI: 0.57 to 2.54). Pre-offshore asbestos exposure (vs no such exposure) was associated with increased risk of pleural mesothelioma (HR=2.06, 95% CI: 1.11 to 3.81). For offshore workers with no pre-offshore asbestos exposure, an increased risk of pleural mesothelioma was found for the highest tertile of average intensity of asbestos (HR=4.13, 95% CI: 0.93 to 18), versus the lowest tertile. No associations were found between RCF and pleural mesothelioma.ConclusionsAssociations between JEM-based offshore asbestos exposure and pleural mesothelioma were confirmed in the NOPW cohort. Pleural mesothelioma risk was also associated with asbestos exposure before work in the offshore petroleum industry.