bluuebunny/crossref_metadata_2025_split huggingface dataset:
QTL mapping of a Brazilian bioethanol strain links the cell wall protein-encoding gene GAS1 to low pH tolerance in S. cerevisiae
Authors: Coradini Alessandro L. V. , da Silveira Bezerra de Mello Fellipe , Furlan Monique , Maneira Carla , Carazzolle Marcelo F. , Pereira Gonçalo Amarante Guimaraes , Teixeira Gleidson Silva 
Published: December 2021

AbstractBackgroundSaccharomyces cerevisiaeis largely applied in many biotechnological processes, from traditional food and beverage industries to modern biofuel and biochemicals factories. During the fermentation process, yeast cells are usually challenged in different harsh conditions, which often impact productivity. Regarding bioethanol production, cell exposure to acidic environments is related to productivity loss on both first- and second-generation ethanol. In this scenario, indigenous strains traditionally used in fermentation stand out as a source of complex genetic architecture, mainly due to their highly robust background—including low pH tolerance.ResultsIn this work, we pioneer the use of QTL mapping to uncover the genetic basis that confers to the industrial strain Pedra-2 (PE-2) acidic tolerance during growth at low pH. First, we developed a fluorescence-based high-throughput approach to collect a large number of haploid cells using flow cytometry. Then, we were able to apply a bulk segregant analysis to solve the genetic basis of low pH resistance in PE-2, which uncovered a region in chromosome X as the major QTL associated with the evaluated phenotype. A reciprocal hemizygosity analysis revealed the alleleGAS1, encoding a β-1,3-glucanosyltransferase, as the casual variant in this region. TheGAS1sequence alignment of distinctS. cerevisiaestrains pointed out a non-synonymous mutation (A631G) prevalence in wild-type isolates, which is absent in laboratory strains. We further showcase thatGAS1allele swap between PE-2 and a low pH-susceptible strain can improve cell viability on the latter of up to 12% after a sulfuric acid wash process.ConclusionThis work revealedGAS1as one of the main causative genes associated with tolerance to growth at low pH in PE-2. We also showcase howGAS1PE-2can improve acid resistance of a susceptible strain, suggesting that these findings can be a powerful foundation for the development of more robust and acid-tolerant strains. Our results collectively show the importance of tailored industrial isolated strains in discovering the genetic architecture of relevant traits and its implications over productivity.
Accurate prediction of acute pancreatitis severity based on genome-wide cell free DNA methylation profiles
Authors: Sun Hong-Wei , Dai Sheng-Jie , Kong Hong-Ru , Fan Jie-Xiang , Yang Fang-Yuan , Dai Ju-Qing , Jin Yue-Peng , Yu Guan-Zhen , Chen Bi-Cheng , Shi Ke-Qing 
Published: December 2021

Abstract
Background
Patients with severe acute pancreatitis (SAP) have a high mortality, thus early diagnosis and interventions are critical for improving survival. However, conventional tests are limited in acute pancreatitis (AP) stratification. We aimed to assess AP severity by integrating the informative clinical measurements with cell free DNA (cfDNA) methylation markers.

Methods
One hundred and seventy-five blood samples were collected from 61 AP patients at multiple time points, plus 24 samples from healthy individuals. Genome-wide cfDNA methylation profiles of all samples were characterized with reduced representative bisulfite sequencing. Clinical blood tests covering 93 biomarkers were performed on AP patients within 24 h. SAP predication models were built based on cfDNA methylation and conventional blood biomarkers separately and in combination.

Results
We identified 565 and 59 cfDNA methylation markers informative for acute pancreatitis and its severity. These markers were used to develop prediction models for AP and SAP with area under the receiver operating characteristic of 0.92 and 0.81, respectively. Twelve blood biomarkers were systematically screened for a predictor of SAP with a sensitivity of 87.5% for SAP, and a specificity of 100% in mild acute pancreatitis, significantly higher than existing blood tests. An expanded model integrating 12 conventional blood biomarkers with 59 cfDNA methylation markers further improved the SAP prediction sensitivity to 92.2%.

Conclusions
These findings have demonstrated that accurate prediction of SAP by the integration of conventional and novel blood molecular markers, paving the way for early and effective SAP intervention through a non-invasive rapid diagnostic test.
COVID-19 and chronic diabetes: the perfect storm for reactivation tuberculosis?: a case series
Authors: Aguillón-Durán Genesis P. , Prieto-Martínez Ericka , Ayala Doris , García Juan , Thomas John M. , García Juan Ignacio , Henry Brandon Michael , Torrelles Jordi B. , Turner Joanne , Ledezma-Campos Eder , Restrepo Blanca I. 
Published: December 2021

Abstract
Background
The coronavirus disease 2019 pandemic is predicted to have a net negative effect on tuberculosis control, with an estimated excess of 6.3 million tuberculosis cases and 1.4 million deaths by 2025. Programmatic issues such as the lockdown of tuberculosis services affect all patients, while biosocial factors have a differential impact on an individual’s risk for tuberculosis or adverse tuberculosis outcomes.

Case presentation
We report three Hispanic cases of incident tuberculosis (two males, 43 and 44 years old; one female, 49 years old) after resolution of coronavirus disease episodes. Coincidentally, all cases shared a common risk factor: a chronic history poorly controlled diabetes.

Conclusions
Our findings alert to the threat posed by the synergy between coronavirus disease and diabetes, on tuberculosis reactivation. In medium- to high-risk settings for tuberculosis, we recommend implementation of routine screening for latent tuberculosis infection in these cases, and preventive tuberculosis treatment in those who are positive.
ViaFuse: Fiji macros to calculate skeletal muscle cell viability and fusion index
Authors: Hinkle Emma Rose , Essader Tasneem Omar , Gentile Gabrielle Marie , Giudice Jimena 
Published: December 2021

Abstract
Background
Measuring biological features of skeletal muscle cells is difficult because of their unique morphology and multinucleate nature upon differentiation. Here, we developed a new Fiji macro package called ViaFuse (that stands for viability and fusion) to measure skeletal muscle cell viability and differentiation. To test ViaFuse, we utilized immunofluorescence images of differentiated myotubes where the capping actin protein of muscle z-line subunit beta (CAPZB) was depleted in comparison with control cells.

Results
We compared the values achieved using the ViaFuse macros first with manual quantification performed by researchers and second with those obtained utilizing the MATLAB muscle-centric software MyoCount. We observed a high degree of correlation between all methods of quantification.

Conclusions
ViaFuse can detect the borders of myotubes and identify nuclear clumps which have been limitations of previous muscle-centric imaging software. The ViaFuse macros require little computer power or space to run and user inputs to the ViaFuse macros are minimal, thereby automating the analysis process in a quick, easy, and accurate fashion. Additionally, the ViaFuse macros work with Fiji, an existing imaging software widely used by skeletal muscle researchers. Furthermore, ViaFuse is compatible with many computer systems, has a very intuitive interface, and does not require prior complex mathematical knowledge. Therefore, we propose ViaFuse as a robust and meticulous method to quantify skeletal muscle cell viability and differentiation.
Protocol for a systematic review and meta-analysis of studies on the use of brain natriuretic peptide and N-terminal brain natriuretic peptide levels in the diagnosis of cardiopulmonary edema in acute respiratory failure
Authors: Terayama Takero , Taniguchi Takuya , Imai Ryosuke , Anan Keisuke , Yoshida Takuo , Ando Koichi , Okamori Satoshi , Okada Yohei 
Published: December 2021

Abstract
Background
Dyspnea with bilateral pulmonary edema is common among patients in emergency departments (EDs) or intensive care units (ICUs). For the initial management of patients with this condition, cardiopulmonary edema (CPE) must be differentiated from acute respiratory distress syndrome (ARDS) in clinical settings. Brain natriuretic peptide (BNP) and N-terminal brain natriuretic peptide (NT-proBNP) are useful in distinguishing these conditions. However, current data about the use of these indexes are limited. Hence, we planned to perform a systematic review and meta-analysis to determine the accuracy of the two indexes for the diagnosis of CPE.

Methods
We designed and registered a study protocol for a systematic review and meta-analysis. This study aims to determine the diagnostic accuracy of BNP and NT-proBNP based on the standards of the methodology of the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy and the Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies in reporting the findings of this review. We will search PubMed (MEDLINE), Cochrane Library, Embase, www.ClinicalTrials.gov, International Clinical Trials Registry Platform, and Google Scholar. Randomized controlled trials, cross-sectional studies, and observational cohort studies reporting the accuracy in diagnosing CPE among adult patients with dyspnea and bilateral pulmonary edema will be included in the analysis. There will be no limits regarding language and publication date for this review. Two reviewers will independently screen articles, extract data, evaluate for quality and bias using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2), and use Grading of Recommendations Assessment, Development and Evaluation to summarize the strength of body of evidence. Then, a meta-analysis will be performed, and different statistical methods will be used to investigate heterogeneity among studies. A subgroup analysis of elderly patients with left ventricular dysfunction or chronic renal dysfunction will be performed. In the meta-analysis, a hierarchical summary receiver operating characteristic model or a bivariate model will be used in each index test, as appropriate.

Discussion
A systematic review and meta-analysis of the accuracy of BNP and NT-proBNP for the diagnosis of CPE will be conducted. The result of this study can help clinicians to identify an appropriate initial treatment for patients with acute respiratory failure, including those with ARDS and CPE. To the best of our knowledge, this will be the first comprehensive systematic review focusing on ARDS management in a specific population.

Systematic review registration
PROSPERO ID CRD42020201576
Two pulse intrusive events of the Pliocene Tanigawa-dake granites revealed from zircon U–Pb dating
Authors: Minami Saki , Nagata Mitsuhiro , Sueoka Shigeru , Fukuda Shoma , Kajita Yuya , Ogita Yasuhiro , Kagami Saya , Yokoyama Tatsunori , Tagami Takahiro 
Published: December 2021

AbstractWe performed zircon U–Pb dating on the Pliocene Tanigawa-dake granites (Makihata and Tanigawa bodies) and the Cretaceous Minakami quartzdiorite, Northeast Japan Arc. Concordia ages were estimated to be 3.95 ± 0.11 Ma (± 2 sigma) for the Makihata body, 3.18 ± 0.13 Ma and 3.32 ± 0.15 Ma for the Tanigawa body, and 109.4 ± 2.2 Ma for the Minakami quartzdiorite. The Minakami quartzdiorite is possibly correlated to the bedrock in the Ashio belt because the age of the Minakami quartzdiorite is consistent with the zircon U–Pb ages of the earliest Tadamigawa granites (107–62 Ma) which are distributed to the northeast of the Tanigawa-dake region and belong to the Ashio belt. All the zircon U–Pb ages of the Tanigawa-dake granites are older than the previously reported cooling ages, i.e., K–Ar ages and zircon fission-track ages, being consistent with their difference in closure temperature. On the basis of these results, we concluded that the intrusive ages of the Tanigawa-dake granites are ~ 4–3 Ma, which are among the youngest exposed plutons on Earth. The U–Pb ages of the Makihata body and the Tanigawa body are different significantly in the 2 sigma error range. Thus, the Tanigawa body intruded later than the Makihata body by ~ 0.7 Myr.
Graphical Abstract
Co-designing genomics research with a large group of donor-conceived siblings
Authors: Nunn Jack S. , Crawshaw Marilyn , Lacaze Paul 
Published: December 2021

Abstract
Background
Human genomics research is growing rapidly. More effective methods are required for co-design and involving people, especially those sub-populations which are inherently high interest to medical research and thus at greater risk of being exploited. This case study documents how we worked with a large group of donor-conceived siblings who share the same sperm donor father, to explore how they might want to engage with and influence any future genomic research.

Method
A participatory action research process was used to explore the views of a group of 18 people who knew they are donor-conceived siblings. They are part of a larger group of up to 1000 people who share the same sperm donor father but the only ones in contact with each other; it is likely that many of the uncontacted siblings are unaware of their biological father, have been unable to trace others or have died. The discussion explored views about how the group would like to be involved in future research. Five members participated in co-design; 12 completed a pre-discussion online survey; and six participated in an online discussion forum and evaluation survey. The online discussion was led by one facilitator, supported by the study team.

Results
Of the 18 siblings approached in 2018, 14 participated in the co-design stages or the surveys and online discussion. Co-design informed the research process. Participants reported enjoying the overall experience of the surveys and discussion forum, which were perceived as inclusive and flexible. Most participants’ views regarding the value of involvement in research changed during the process, and ‘widened’ about who should be involved. Participants were supportive of future research being done with the siblings group. All who completed the final survey requested to remain part of the co-design process. Other themes in the online discussion included concerns about conflicting interests and a desire for research participation to improve the situation for people affected by assisted conception. The process informed later discussions in the sibling group about participating in a self-managed biobank and informed decision making about participating in genomics research.

Conclusion
Findings from this study help inform ways in which people from certain sub-populations can be involved in planning and defining their participation in genomic research, particularly those that are inherently high interest to medical research and thus at greater risk of exploitation. This process provides a replicable method of involving potential participants in co-designing genomics research using online discussions, with positive outcomes. Reporting this study using ‘Standardised data on initiatives (STARDIT)’ to report the process allows comparison with other studies.
Nonhyperbolic normal moveout stretch correction with deep learning automation
Authors: Abedi Mohammad Mahdi , Pardo David 
Published: December 2021

Normal-moveout (NMO) correction is a fundamental step in seismic data processing. It consists of mapping seismic data from recorded traveltimes to corresponding zero-offset times. This process produces wavelet stretching as an undesired by-product. We have addressed the NMO stretching problem with two methods: (1) an exact stretch-free NMO correction that prevents the stretching of primary reflections and (2) an approximate post-NMO stretch correction. Our stretch-free NMO produces parallel moveout trajectories for primary reflections. Our post-NMO stretch correction calculates the moveout of stretched wavelets as a function of offset. Both methods are based on the generalized moveout approximation and are suitable for application in complex anisotropic or heterogeneous environments. We use new moveout equations, modify the original parameter functions to be a constant over the primary reflections, and then interpolate the seismogram amplitudes at the calculated traveltimes. For fast and automatic modification of the parameter functions, we use deep learning. We design a deep neural network (DNN) using convolutional layers and residual blocks. To train the DNN, we generate a set of 40,000 synthetic NMO-corrected common-midpoint gathers and the corresponding desired outputs of the DNN. The data set is generated using different velocity profiles, wavelets, and offset vectors, and it includes multiples, ground roll, and band-limited random noise. The simplicity of the DNN task — a 1D identification of primary reflections — improves the generalization in practice. We use the trained DNN and find successful applications of our stretch-correction method on synthetic and different real data sets.
Early Intervention in Psychosis services: A systematic review and narrative synthesis of the barriers and facilitators to implementation
Authors: O’Connell N. , O’Connor K. , McGrath D. , Vagge L. , Mockler D. , Jennings R. , Darker C. D. 
Published: December 2021

AbstractBackgroundEarly intervention in psychosis (EIP) services target the early manifestation of psychosis and provide multidisciplinary care. They demonstrate effectiveness and cost-effectiveness. Implementation of EIP services is inconsistent and piecemeal. This systematic review and narrative synthesis aims to identify barriers and facilitators to EIP service implementation.MethodsWe conducted an electronic search of databases (EMBASE, Medline, Web of Science, and PsychINFO) to detect papers reporting EIP service implementation findings and associated barriers and facilitators. The search occurred between June to August 2020, and again in January 2021. Articles meeting inclusion criteria were extracted and narratively synthesized. A quality assessment was conducted using the Mixed Methods Appraisal Tool.ResultsTwenty-three studies were selected. The most common study design was descriptive accounts of implementation. Patient age ranged varied from 14 to 35 years. We identified three barrier and facilitator domains: (a) system; (b) services; and (c) staff, and a range of subdomains. The most frequent subdomains were “funding” and “strength of collaboration and communication between EIP and outside groups and services”. Associations between domains and subdomains were evident, particularly between systems and services.ConclusionsA range of barriers and facilitators to EIP implementation exist. Some of these are generic factors germane across health systems and services, while others are specific to EIP services. A thorough prior understanding of these challenges and enablers are necessary before implementation is attempted. Accounting for these issues within local and national contexts may help predict and increase the likelihood of services’ success, stability, and longevity.
Western Honduras Copán Population–Based Cancer Registry: Initial Estimates and a Model for Rural Central America
Authors: Norwood Dalton Argean , Montalvan-Sanchez Eleazar Enrique , Corral Juan E. , Estévez-Ordoñez Dagoberto , Paredes Andrea A. , Domínguez Lucia B. , Rodríguez Aida A. , Bravo Luis E. , Morgan Douglas R. , Domínguez Ricardo L. 
Published: December 2021

PURPOSE Population-based cancer registries (PBCRs) are critical for national cancer control planning, yet few low- and middle-income countries (LMICs) have quality PBCRs. The Central America Four region represents the principal LMIC region in the Western hemisphere. We describe the establishment of a PBCR in rural Western Honduras with first estimates for the 2013-2017 period. METHODS The Western Honduras PBCR was established through a collaboration of academic institutions and the Honduras Ministry of Health for collection of incident cancer data from public and private health services. Data were recorded using the Research Electronic Data Capture (REDCap) web-based platform with data monitoring and quality checks. Crude and age-standardized rates (ASRs) were calculated at the regional level, following WHO methodology. RESULTS The web-based platform for data collection, available ancillary data services (eg, endoscopy), and technical support from international centers (United States and Colombia) were instrumental for quality control. Crude cancer incidence rates were 112.2, 69.8, and 154.6 per 100,000 habitants overall, males, and females, respectively (excluding nonmelanoma skin cancer). The adjusted ASRs were 84.2, 49.6, and 118.9 per 100,000 overall habitants, males, and females, respectively. The most common sites among men were stomach (ASR 26.0, 52.4%), colorectal (ASR 5.11, 10.15%), and prostate (ASR 2.7, 5.4%). The most common sites in women were cervix (ASR 34.2, 36.7%), breast (ASR 11.2, 12.3%), and stomach (ASR 10.8, 11.7%). CONCLUSION The Copán-PBCR represents a successful model to develop cancer monitoring in rural LMICs. Innovations included the use of the REDCap platform and leverage of Health Ministry resources. This provides the first PBCR data for Honduras and the Central America Four and confirms that infection-driven cancers, such as gastric and cervical, should be priority targets for cancer control initiatives.
Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study
Authors: Budde Lihua E. , Assouline Sarit , Sehn Laurie H. , Schuster Stephen J. , Yoon Sung-Soo , Yoon Dok Hyun , Matasar Matthew J. , Bosch Francesc , Kim Won Seog , Nastoupil Loretta J. , Flinn Ian W. , Shadman Mazyar , Diefenbach Catherine , O'Hear Carol , Huang Huang , Kwan Antonia , Li Chi-Chung , Piccione Emily C. , Wei Michael C. , Yin Shen , Bartlett Nancy L. 
Published: December 2021

PURPOSE Mosunetuzumab is a bispecific antibody targeting CD20 and CD3 that redirects T cells to engage and eliminate malignant B cells and is being developed for relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs). METHODS This first-in-human trial (ClinicalTrials.gov identifier: NCT02500407 ) evaluated the safety and tolerability and efficacy of mosunetuzumab in patients with R/R B-NHL and established the recommended phase II dose. Data from dose escalation are presented. Single-agent mosunetuzumab was administered intravenously in 3-week cycles, at full dose in cycle 1 day 1 (group A) or with ascending (step-up) doses during cycle 1 on days 1, 8, and 15 (group B), for eight or 17 cycles on the basis of tumor response. RESULTS Two hundred thirty patients were enrolled. Doses up to 2.8 mg and 60 mg were assessed in groups A and B, respectively; maximum tolerated dose was not exceeded. In group B (n = 197), common adverse events (≥ 20% of patients) were neutropenia (28.4%), cytokine release syndrome (27.4%), hypophosphatemia (23.4%), fatigue (22.8%), and diarrhea (21.8%). Cytokine release syndrome was mostly low-grade (grade ≥ 3: 1.0%) and mainly confined to cycle 1. Across the doses investigated (group B), best overall response rates were 34.9% and 66.2% in patients with aggressive and indolent B-NHL, respectively, and complete response rates were 19.4% and 48.5%. Among patients with a complete response, the median duration of response was 22.8 months (95% CI, 7.6 to not estimable) and 20.4 (95% CI, 16 to not estimable) in patients with aggressive and indolent B-NHL, respectively. CONCLUSION Mosunetuzumab, administered with step-up dosing, has a manageable safety profile and induces durable complete responses in R/R B-NHL. The expansion stage of the study is ongoing at the dose level of 1/2/60/60/30 mg selected for further study.