bluuebunny/crossref_metadata_2025_split huggingface dataset:
A three-gene cluster in Trichoderma reesei reveals a potential role of dmm2 in DNA repair and cellulase production
Authors: Cai Wanchuan , Chen Yumeng , Zhang Lei , Fang Xu , Wang Wei 
Published: March 2022

Abstract
Background
The ascomycete Trichoderma reesei is one of the most efficient industrial producers of cellulase. Gene targeting by homologous recombination is a key technique for improving strains and constructing mutants. In T. reesei, tku70 (homologous to human KU70) was deleted to block non-homologous end-joining, which led to 95% of transformants exhibiting homologous recombination.

Results
Two genes located in close proximity to tku70 were identified: the ferrochelatase gene hem8 (tre78582, homologous to Aspergillus niger hemH and Cryptococcus neoformans HEM15) and a putative DNA methylation modulator-2 gene dmm2 (tre108087, homologous to Neurospora crassa dmm-2). Genome-wide surveys of 324 sequenced fungal genomes revealed that the homologues of the three genes of interest are encoded in tandem in most Sordariomycetes. The expression of this three-gene cluster is regulated by blue light. The roles of these three genes were analyzed via deletion and complementation tests. The gene hem8 was originally described as a novel and highly distinct auxotrophic marker in T. reesei and we found that the product protein, HEM8, catalyzes the final step in heme biosynthesis from highly photoreactive porphyrins. The lethal phenotype of the hem8 deletion could be overcome by hematin supplementation. We also studied the functions of tku70 and dmm2 in DNA repair using mutagen sensitivity experiments. We found that the Δtku70 strain showed increased sensitivity to bleomycin, which induces DNA double-strand breaks, and that the Δdmm2 strain was sensitive to bleomycin, camptothecin (an inhibitor of type I topoisomerases), and hydroxyurea (a deoxynucleotide synthesis inhibitor). The double-mutant Δtku70&dmm2 showed higher sensitivity to hydroxyurea, camptothecin, and bleomycin than either of the single mutants. Knockout of dmm2 significantly increased cellulase production.

Conclusions
Our data show, for the first time, that ferrochelatase encoded by hem8 catalyzes the final step in heme biosynthesis from highly photoreactive porphyrins and that dmm2 encodes a putative DNA methylation modulator-2 protein related to DNA repair and cellulase expression in T. reesei. Our data provide important insights into the roles of this three-gene cluster in T. reesei and other Sordariomycetes and show that the DNA methylation modulator DMM2 affects cellulase gene expression in T. reesei.
An 8-gene machine learning model improves clinical prediction of severe dengue progression
Authors: Liu Yiran E. , Saul Sirle , Rao Aditya Manohar , Robinson Makeda Lucretia , Agudelo Rojas Olga Lucia , Sanz Ana Maria , Verghese Michelle , Solis Daniel , Sibai Mamdouh , Huang Chun Hong , Sahoo Malaya Kumar , Gelvez Rosa Margarita , Bueno Nathalia , Estupiñan Cardenas Maria Isabel , Villar Centeno Luis Angel , Rojas Garrido Elsa Marina , Rosso Fernando , Donato Michele , Pinsky Benjamin A. , Einav Shirit , Khatri Purvesh 
Published: March 2022

Abstract
Background
Each year 3–6 million people develop life-threatening severe dengue (SD). Clinical warning signs for SD manifest late in the disease course and are nonspecific, leading to missed cases and excess hospital burden. Better SD prognostics are urgently needed.

Methods
We integrated 11 public datasets profiling the blood transcriptome of 365 dengue patients of all ages and from seven countries, encompassing biological, clinical, and technical heterogeneity. We performed an iterative multi-cohort analysis to identify differentially expressed genes (DEGs) between non-severe patients and SD progressors. Using only these DEGs, we trained an XGBoost machine learning model on public data to predict progression to SD. All model parameters were “locked” prior to validation in an independent, prospectively enrolled cohort of 377 dengue patients in Colombia. We measured expression of the DEGs in whole blood samples collected upon presentation, prior to SD progression. We then compared the accuracy of the locked XGBoost model and clinical warning signs in predicting SD.

Results
We identified eight SD-associated DEGs in the public datasets and built an 8-gene XGBoost model that accurately predicted SD progression in the independent validation cohort with 86.4% (95% CI 68.2–100) sensitivity and 79.7% (95% CI 75.5–83.9) specificity. Given the 5.8% proportion of SD cases in this cohort, the 8-gene model had a positive and negative predictive value (PPV and NPV) of 20.9% (95% CI 16.7–25.6) and 99.0% (95% CI 97.7–100.0), respectively. Compared to clinical warning signs at presentation, which had 77.3% (95% CI 58.3–94.1) sensitivity and 39.7% (95% CI 34.7–44.9) specificity, the 8-gene model led to an 80% reduction in the number needed to predict (NNP) from 25.4 to 5.0. Importantly, the 8-gene model accurately predicted subsequent SD in the first three days post-fever onset and up to three days prior to SD progression.

Conclusions
The 8-gene XGBoost model, trained on heterogeneous public datasets, accurately predicted progression to SD in a large, independent, prospective cohort, including during the early febrile stage when SD prediction remains clinically difficult. The model has potential to be translated to a point-of-care prognostic assay to reduce dengue morbidity and mortality without overwhelming limited healthcare resources.
Asymptomatic foot and ankle structural injuries: a 3D imaging and finite element analysis of elite fencers
Authors: Lu Congfei , Fan Yuxuan , Yu Genyu , Chen Hua , Sinclair Jonathan , Fan Yifang 
Published: March 2022

Abstract
Background
Fencing is a highly asymmetrical combat sport, that imposes high mechanical demands over repeated exposures on the musculoskeletal structures, a primary cause of injuries in fencers. However, there are limited epidemiological studies on the structural injuries of the foot and ankle in fencers. This study aimed to investigate foot and ankle structural injuries, and explore how metatarsophalangeal joint structural changes may affect the mechanisms of foot and ankle injuries in asymptomatic fencers.

Methods
3D images of foot and ankle morphology using computed tomography were obtained from ten elite fencers. We then constructed finite element models of the first metatarsophalangeal joint in the foot of their trail legs. The validated models were used to simulate stress distribution changes from different ankle joint angles during lunging.

Results
The findings showed that stress distribution changes at the medial and lateral sesamoid may have caused sesamoid fractures, and that habitual and concentrated stress on the metatarsal bones might have flattened the sesamoid groove. This process may damage the integrity of the first metatarsophalangeal joint, and consequently affect the efficiency of the windlass mechanism in fencers. During lunging, different ankle joint angles of the trail foot increased the total stress difference of the medial and lateral foot, and thus influenced the lunging quality and its stability.

Conclusions
Our findings revealed that the asymmetric nature of fencing might have caused asymptomatic foot and ankle structural injuries, and finite element analysis results indicated that this might increase the incidence of the serious injuries if unattended. Regular computed tomography examination should be introduced to monitor elite fencers’ lower limb alterations, permitting unique angle adjustments in the trail foot without sacrificing technical or physiologic properties based on the exam results and reduce the lower limb injury risk.
Transcriptome resequencing data for rock pigeon (Columba livia)
Authors: Kharrati-Koopaee Hamed , Esmailizadeh Ali , Sabahi Fatemeh 
Published: March 2022

Abstract
Objective
How do birds navigate their way? It is one of the interesting question about homing pigeons, however the genetic of navigation has reminded as a puzzle. Optic lobe, olfactory bulb, hippocampus and cere were collected for RNA sampling. The generated RNA-seq represent RNA resequencing data for racing homer (homing) pigeon and other rock pigeon breeds. The obtained data set can provide new insight about hippocampus role and GSR contribution to pigeon magnetoreception.

Data description
To investigate the navigation ability of rock pigeon breeds, 60 whole transcriptome sequence data sets related to homing pigeon, Shiraz tumblers, feral pigeons and Persian high flyers were obtained. RNA extraction was performed from three brain regions (optic lobe, olfactory bulb, hippocampus) and cere. Paired-end 150 bp short reads (Library size 350 bp) were sequenced by Illumina Hiseq 2000. In this way, about 342.1 Gbp and 130.3 Gb data were provided. The whole transcriptome data sets have been deposited at the NCBI SRA database (PRJNA532674). The submitted data set may play critical role to describe the mechanism of navigation ability of rock pigeon breeds.
Efficacy of SGLT2 inhibitors as additional treatment in Japanese type 2 diabetic patients: second or third choice?
Authors: Fujiwara Makoto , Shimizu Masaru , Maejima Yuko , Shimomura Kenju 
Published: March 2022

Abstract
Objectives
Due to the increase of type 2 diabetes (T2D), the number of patients in treatment with multiple anti-diabetic agents is increased. According to the recent recommendation of treatment guidelines, sodium-glucose cotransporter 2 (SGLT2) inhibitors would be used as additional treatment to the currently administered anti-diabetic drugs for poorly controlled T2D patients. Here, we assessed the efficacy of SGLT2 inhibitors added to the current treatment with metformin, dipeptidyl peptidase-4 (DPP4) inhibitors, or both in Japanese T2D patients.

Results
Japanese T2D subjects with poor glucose control, who were treated with metformin (n = 10), DPP4 inhibitors (n = 11), or both (n = 28) and who were in need of additional treatment, were recruited. HbA1c levels before and 6 months after addition of SGLT2 inhibitor treatment were used to compare the effectiveness. The HbA1c levels after addition of SGLT2 inhibitors significantly decreased in all groups. The change in HbA1c levels (delta HbA1c) showed no significant difference between the three groups. The present data indicated that addition of SGLT2 inhibitors to metformin and/or DPP4 inhibitors is equally effective in the treatment of Japanese T2D patients.
Epigenome-wide DNA methylation profiling of conditioned pain modulation in individuals with non-specific chronic low back pain
Authors: Goodin Burel R. , Overstreet Demario S. , Penn Terence M. , Bakshi Rahm , Quinn Tammie L. , Sims Andrew , Ptacek Travis , Jackson Pamela , Long D. Leann , Aroke Edwin N. 
Published: March 2022

Abstract
Background
The pathoanatomic cause of chronic low back pain (cLBP) cannot be identified for up to 90% of individuals. However, dysfunctional processing of endogenous nociceptive input, measured as conditioned pain modulation (CPM), has been associated with cLBP and may involve changes in neuronal gene expression. Epigenetic-induced changes such as DNA methylation (DNAm) have been associated with cLBP.

Methods
In the present study, the relationship between CPM and DNAm changes in a sample of community-dwelling adults with nonspecific cLBP (n = 48) and pain-free controls (PFC; n = 50) was examined using reduced representation bisulfite sequencing. Gene ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied to identify key pathways involved in efficient versus deficient CPM.

Results
Based on CPM efficiency, we identified 6006 and 18,305 differentially methylated CpG sites (DMCs) with q values < 0.01 among individuals with cLBP and PFCs, respectively. Most of the DMCs were hypomethylated and annotated to genes of relevance to pain, including OPRM1, ADRB2, CACNA2D3, GNA12, LPL, NAXD, and ASPHD1. In both cLBP and PFC groups, the DMCs annotated genes enriched many GO terms relevant to pain processing, including transcription regulation by RNA polymerase II, nervous system development, generation of neurons, neuron differentiation, and neurogenesis. Both groups also enriched the pathways involved in Rap1-signaling, cancer, and dopaminergic neurogenesis. However, MAPK-Ras signaling pathways were enriched in the cLBP, not the PFC group.

Conclusions
This is the first study to investigate the genome-scale DNA methylation profiles of CPM phenotype in adults with cLBP and PFCs. Based on CPM efficiency, fewer DMC enrichment pathways were unique to the cLBP than the PFCs group. Our results suggest that epigenetically induced modification of neuronal development/differentiation pathways may affect CPM efficiency, suggesting novel potential therapeutic targets for central sensitization. However, CPM efficiency and the experience of nonspecific cLBP may be independent. Further mechanistic studies are required to confirm the relationship between CPM, central sensitization, and nonspecific cLBP.
Combining plasma phospho-tau and accessible measures to evaluate progression to Alzheimer’s dementia in mild cognitive impairment patients
Authors: Pichet Binette Alexa , Palmqvist Sebastian , Bali Divya , Farrar Gill , Buckley Christopher J. , Wolk David A. , Zetterberg Henrik , Blennow Kaj , Janelidze Shorena , Hansson Oskar 
Published: March 2022

Abstract
Background
Up to now, there are no clinically available minimally invasive biomarkers to accurately identify mild cognitive impairment (MCI) patients who are at greater risk to progress to Alzheimer’s disease (AD) dementia. The recent advent of blood-based markers opens the door for more accessible biomarkers. We aimed to identify which combinations of AD related plasma biomarkers and other easily accessible assessments best predict progression to AD dementia in patients with mild cognitive impairment (MCI).

Methods
We included patients with amnestic MCI (n = 110) followed prospectively over 3 years to assess clinical status. Baseline plasma biomarkers (amyloid-β 42/40, phosphorylated tau217 [p-tau217], neurofilament light and glial fibrillary acidic protein), hippocampal volume, APOE genotype, and cognitive tests were available. Logistic regressions with conversion to amyloid-positive AD dementia within 3 years as outcome was used to evaluate the performance of different biomarkers measured at baseline, used alone or in combination. The first analyses included only the plasma biomarkers to determine the ones most related to AD dementia conversion. Second, hippocampal volume, APOE genotype and a brief cognitive composite score (mPACC) were combined with the best plasma biomarker.

Results
Of all plasma biomarker combinations, p-tau217 alone had the best performance for discriminating progression to AD dementia vs all other combinations (AUC 0.84, 95% CI 0.75–0.93). Next, combining p-tau217 with hippocampal volume, cognition, and APOE genotype provided the best discrimination between MCI progressors vs. non-progressors (AUC 0.89, 0.82–0.95). Across the few best models combining different markers, p-tau217 and cognition were consistently the main contributors. The most parsimonious model including p-tau217 and cognition had a similar model fit, but a slightly lower AUC (0.87, 0.79–0.95, p = 0.07).

Conclusion
We identified that combining plasma p-tau217 and a brief cognitive composite score was strongly related to greater risk of progression to AD dementia in MCI patients, suggesting that these measures could be key components of future prognostic algorithms for early AD.

Trial registration
NCT01028053, registered December 9, 2009.
MRI in female pelvis: an ESUR/ESR survey
Authors: Nougaret Stephanie , Lakhman Yulia , Gourgou Sophie , Kubik-Huch Rahel , Derchi Lorenzo , Sala Evis , Forstner Rosemarie ,   the European Society of Radiology (ESR) and the European Society of Urogenital Radiology (ESUR)
Published: March 2022

Abstract
Objectives
While magnetic resonance imaging (MRI) is considered the gold standard for the imaging of female pelvis, there is an ongoing debate about the most appropriate indications and optimal imaging protocols. The European Society of Urogenital Radiology (ESUR) launched a survey to evaluate the current utilization of female pelvic MRI in clinical practice.

Methods
The ESUR female imaging subgroup developed an online survey that was then approved by the ESR board and circulated among the ESR members. The questions in the survey encompassed training and experience, indications for imaging and MR imaging protocols, reporting styles and preferences. The results of the survey were tabulated, and subgroups were compared using χ2 test.

Results
A total of 5900 ESR members with an interest in both MRI and female pelvic imaging were invited to participate; 840 (14.23%) members completed the survey. Approximately 50% of respondents were academic radiologists (50.6%) and nearly 60% women (59.69%). One third of the respondents were subspecialized in Gynecological imaging. Nearly half of the survey participants were aware of the presence of ESUR guidelines for imaging of the female pelvis (47.1%). The adoption of the ESUR recommendations was higher among subspecialized and/or academic and/or senior and/or European radiologists compared to all others. The current ESUR recommendations about female pelvic MRI protocols were generally followed. However wide variations in practice were identified with respect to the use of contrast media.

Conclusion
Female pelvic MRI protocol was generally following the ESUR recommendations, especially among subspecialized and academic radiologists. However, the fact that they are followed by only half of the participants highlights the need for wider awareness of these recommendations.
The utility of splenic imaging parameters in cardiac magnetic resonance for the diagnosis of immunoglobulin light-chain amyloidosis
Authors: Lama Niki , Briasoulis Alexandros , Karavasilis Efstratios , Stamatelopoulos Kimon , Chasouraki Angeliki , Alexopoulou Efthymia , Spiliopoulos Stavros , Theodorakakou Foteini , Dimopoulos Meletios Athanasios , Kastritis Efstathios , Kelekis Nikolaos L. 
Published: March 2022

Abstract
Objectives
Cardiac magnetic resonance (CMR) imaging is a key test in the diagnosis of cardiac amyloidosis (CA). Extracardiac involvement is common in light chain (AL) amyloidosis and MRI findings may assist in its diagnosis. We sought to investigate the utility of splenic CMR parameters for the diagnosis of CA.

Methods
Thirty-four patients with AL amyloidosis and 32 patients with severe left ventricular hypertrophy in the setting of aortic stenosis (LVH-AS) who completed 3T cardiac MRI at the time of their diagnosis of AL or LVH-AS were assessed with T1, T2 (modified Look-Locker inversion recovery), extracellular volume (ECV) mapping, and late gadolinium enhancement (LGE) imaging of the heart and spleen.

Results
Age, left ventricular mass index, wall thickness, ejection fraction, and splenic dimensions did not differ significantly between groups. All AL patients had cardiac involvement. T1 and T2 spleen mapping did not differ significantly between groups but AL patients had higher median ECV in the spleen than in LVH-AS (AL 46.9%, LVH-AS: 31%, p < 0.001), and significantly lower short tau inversion recovery ratio (AL: 1.7, LVH-AS: 2.7, p < 0.001) both with very good diagnostic performance to diagnose AL. We identified 16 AL patients with spleen involvement and 16 without. Spleen ECV and “normalized” spleen ratio, defined as the ratio of spleen LGE to muscle values exhibited strong correlation and had excellent diagnostic performance to discriminate those with spleen involvement.

Conclusion
Our findings show that spleen CMR parameters can identify spleen involvement in AL patients and differentiate them from those without AL amyloidosis.
Impact of defacing on automated brain atrophy estimation
Authors: Rubbert Christian , Wolf Luisa , Turowski Bernd , Hedderich Dennis M. , Gaser Christian , Dahnke Robert , Caspers Julian ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: March 2022

Abstract
Background
Defacing has become mandatory for anonymization of brain MRI scans; however, concerns regarding data integrity were raised. Thus, we systematically evaluated the effect of different defacing procedures on automated brain atrophy estimation.

Methods
In total, 268 Alzheimer’s disease patients were included from ADNI, which included unaccelerated (n = 154), within-session unaccelerated repeat (n = 67) and accelerated 3D T1 imaging (n = 114).
Atrophy maps were computed using the open-source software veganbagel for every original, unmodified scan and after defacing using afni_refacer, fsl_deface, mri_deface, mri_reface, PyDeface or spm_deface, and the root-mean-square error (RMSE) between z-scores was calculated.
RMSE values derived from unaccelerated and unaccelerated repeat imaging served as a benchmark. Outliers were defined as RMSE > 75th percentile and by using Grubbs’s test.

Results
Benchmark RMSE was 0.28 ± 0.1 (range 0.12–0.58, 75th percentile 0.33).
Outliers were found for unaccelerated and accelerated T1 imaging using the 75th percentile cutoff: afni_refacer (unaccelerated: 18, accelerated: 16), fsl_deface (unaccelerated: 4, accelerated: 18), mri_deface (unaccelerated: 0, accelerated: 15), mri_reface (unaccelerated: 0, accelerated: 2) and spm_deface (unaccelerated: 0, accelerated: 7). PyDeface performed best with no outliers (unaccelerated mean RMSE 0.08 ± 0.05, accelerated mean RMSE 0.07 ± 0.05).
The following outliers were found according to Grubbs’s test: afni_refacer (unaccelerated: 16, accelerated: 13), fsl_deface (unaccelerated: 10, accelerated: 21), mri_deface (unaccelerated: 7, accelerated: 20), mri_reface (unaccelerated: 7, accelerated: 6), PyDeface (unaccelerated: 5, accelerated: 8) and spm_deface (unaccelerated: 10, accelerated: 12).

Conclusion
Most defacing approaches have an impact on atrophy estimation, especially in accelerated 3D T1 imaging. Only PyDeface showed good results with negligible impact on atrophy estimation.
Structural failure in bridging stentgrafts for branched endovascular aneurysm repair: a case–control study
Authors: Hauck Sven R. , Kupferthaler Alexander , Freund Martin C. , Pichler Peter , Stelzmüller Marie-Elisabeth , Burghuber Christopher , Ehrlich Marek , Teufelsbauer Harald , Loewe Christian , Funovics Martin A. 
Published: March 2022

Abstract
Objective
To present a case series of spontaneous structural failure of bridging stentgrafts (BSGs) after branched endovascular aortic repair (bEVAR), as well as their failure types and their detection. While bEVAR is a safe and effective procedure, one main limitation is the reintervention rate associated with the BSGs. Structural failure of BSGs, defined as fabric disruption, stent fracture with leak or complete separation is a major cause for reinterventions and difficult to detect in computed tomography angiography (CTA).

Methods
From a multicenter bEVAR complication database, structural BSG failures were identified. Patient and BSG characteristics, detection mode, failure type, treatment and outcome were recorded and compared with bEVAR patients with intact BSGs.

Results
Twenty-three BSG failures were detected in 12 patients with only 43% directly identified in CTA, after a mean of 21.4 months after implantation. The BSGs were Advanta (n = 4), E-Ventus (n = 16) and BeGraft (n = 3) in 10 renal, 9 superior mesenteric, and 4 celiac branches. Religning with another BSG was successful in 20/22 cases, one BSG failure necessitated renal branch embolization (organ loss), and one mesenteric bypass surgery. Two reintervention-related mortalities occurred.

Conclusion
Structural failure of BSGs is a serious limitation for bEVAR, which can result in high reintervention rates and serious complications. BSG failure typically occurs in single-layer types and events are clustered in patients. The necessary reinterventions carry serious morbidity and mortality. Since the use as BSG in bEVAR is off-label with all current BSG manufacturers, caution is advised regarding patient-informed consent.