bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequency of Withdrawal of Life-Sustaining Therapy for Perceived Poor Neurologic Prognosis
Authors: Steinberg Alexis , Abella Benjamin S. , Gilmore Emily J. , Hwang David Y. , Kennedy Niki , Lau Winnie , Mullen Isabelle , Ravishankar Nidhi , Tisch Charlotte F. , Waddell Adam , Wallace David J. , Zhang Qiang , Elmer Jonathan 
Published: July 2021

OBJECTIVES:
To measure the frequency of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis among decedents in hospitals of different sizes and teaching statuses.

DESIGN:
We performed a multicenter, retrospective cohort study.

SETTING:
Four large teaching hospitals, four affiliated small teaching hospitals, and nine affiliated nonteaching hospitals in the United States.

PATIENTS:
We included a sample of all adult inpatient decedents between August 2017 and August 2019.

MEASUREMENTS AND MAIN RESULTS:
We reviewed inpatient notes and categorized the immediately preceding circumstances as withdrawal of life-sustaining therapy for perceived poor neurologic prognosis, withdrawal of life-sustaining therapy for nonneurologic reasons, limitations or withholding of life support or resuscitation, cardiac death despite full treatment, or brain death. Of 2,100 patients, median age was 71 years (interquartile range, 60–81 yr), median hospital length of stay was 5 days (interquartile range, 2–11 d), and 1,326 (63%) were treated at four large teaching hospitals. Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis occurred in 516 patients (25%) and was the sole contributing factor to death in 331 (15%). Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis was common in all hospitals: 30% of deaths at large teaching hospitals, 19% of deaths in small teaching hospitals, and 15% of deaths at nonteaching hospitals. Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis happened frequently across all hospital units. Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis contributed to one in 12 deaths in patients without a primary neurologic diagnosis. After accounting for patient and hospital characteristics, significant between-hospital variability in the odds of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis persisted.

CONCLUSIONS:
A quarter of inpatient deaths in this cohort occurred after withdrawal of life-sustaining therapy for perceived poor neurologic prognosis. The rate of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis occurred commonly in all type of hospital settings. We observed significant unexplained variation in the odds of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis across participating hospitals.
Improved Surgical Outcome with Double Incision and Free Nipple Graft in Gender Confirmation Mastectomy
Authors: Kamali Alexander , Sigurjónsson Hannes , Gran Isak , Farnebo Filip , Conneryd Lundgren Kalle , Granath Fredrik , Sommar Pehr 
Published: July 2021

Background:
Mastectomy and chest-wall contouring is the most common gender confirmation surgery. With increasing prevalence of transgender individuals, there is a demand for better surgical outcomes and aesthetic results. Our aim was to evaluate surgical techniques used and assess modifications in gender confirmation mastectomies at Karolinska University hospital in Stockholm, Sweden.

Methods:
A retrospective cohort study was performed on 464 patients undergoing gender confirmation mastectomies in our department between 2009 and 2018. Patient demographics, psychiatric comorbidity, surgical method, and outcome were analyzed. Follow-up was at least one year.

Results:
The most frequently used surgical technique for gender confirmation mastectomies was double incision with free nipple graft (243 patients, 52.4%), followed by periareolar incision (113 patients, 24.4%) and semicircular incision (67 patients, 14.4%). The double incision technique and periareolar technique were associated with 18.9% and 28.3% complications, 3.3% and 12.4% acute reoperations, 28.4% and 65.5% secondary revisions, respectively. The double incision technique increased from being used in 17.8% of all mastectomies during 2009–2013 to 62.9% during 2014–2018, while periareolar incision decreased from 43.0% to 18.5%.

Conclusions:
The current study describes a successful transition of surgical technique from periareolar incision to double incision with free nipple graft in gender confirmation mastectomy, leading to significant improvements in the overall outcome with fewer complications, less acute reoperations and less secondary corrections. Hence, we consider the double incision with free nipple graft technique to be the favored technique in the vast majority of cases in female-to-male chest wall contouring.
OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY EVALUATION OF PERIPAPILLARY MICROVASCULAR CHANGES AFTER RHEGMATOGENOUS RETINAL DETACHMENT REPAIR
Authors: Bonfiglio Vincenza , Ortisi Elina , Nebbioso Marcella , Reibaldi Michele , Lupidi Marco , Russo Andrea , Fallico Matteo , Scollo Davide , Macchi Iacopo , Pizzo Alessandra , Panebianco Roberta , Patanè Clara , Vadalà Maria , Toro Mario D. , Rejdak Robert , Nowomiejska Katarzyna , Avitabile Teresio , Longo Antonio 
Published: July 2021

Purpose:
To evaluate the radial peripapillary capillary plexus (RPCP) vessel density (VD) and the retinal nerve fiber layer (RNFL) thickness in eyes successfully treated with pars plana vitrectomy for primary rhegmatogenous retinal detachment.

Methods:
In this cross-sectional multicenter clinical study, eyes with a minimum 12-month follow-up were reexamined. The RPCP VD and RNFL thickness in the rhegmatogenous retinal detachment subfields of the affected eye (study group) were compared with the corresponding areas of the healthy fellow eyes (control group).

Results:
Fifty-three eyes were included in the study. A significantly lower RPCP VD and RNFL thickness were observed in those subfields affected by rhegmatogenous retinal detachment compared with those of the control group (P < 0.001). No statistically significant differences were observed between undetached subfields in the study group and their corresponding images in the control group. In the study group, a significant correlation was found between RPCP VD and RNFL thickness in subfields with detached retina (r = 0.393, P < 0.001) and undetached retina (r = 0.321, P < 0.001).

Conclusion:
Radial peripapillary capillary plexus VD changes were found in the subfields of detached retina successfully treated with pars plana vitrectomy and they correlated with RNFL thinning. These data suggest a coexistence of neuronal and microvascular damage in patients affected by rhegmatogenous retinal detachment.
Avoiding the blood supply to the femoral head during cannulated screw fixation: A comparison of two techniques
Authors: Pettett Brett J. , Winek Nathan C. , Schimoler Patrick J. , Kharlamov Alexander , Miller Mark Carl , Westrick Edward R. 
Published: July 2021

Abstract

Objectives:
To compare the strength of the inverted triangle (IT) versus the L-shaped cannulated screw fixation technique for stabilizing a Pauwels 2 femoral neck fracture. To demonstrate the risk to the blood supply to the femoral head from a posterior–superior screw.

Methods:
The IT construct was compared with the L-shaped design in 10 composite femurs. A Pauwels 2 fracture was made with a 5 mm gap. Each specimen was loaded over 5000 cycles, measuring angular/shear displacement then loaded to failure. The data were analyzed using Mann–Whitney U test. Three separate fresh frozen cadavers were injected with low-viscosity epoxy. The intraosseous bloody supply was inspected in each femoral head (no fixation, IT, L-shaped).

Results:
There was no difference in angular (P = .3) or shear displacement (P = .99) between either screw design after cyclical loading. Also, there was not statistical difference in load to failure testing between either construct (P = .99). The average load to failure in the IT group was 3204.4 N. The average was 3180.2 N in the L-shaped design. We demonstrated the presence of the intraosseous portion of the lateral epiphyseal vessel in the specimen without screw fixation. This was preserved in the specimen with the L-shaped design but absent in the specimen following IT fixation.

Conclusions:
The strength of the L-shaped construct was not statistically different than the strength of the IT design. The posterior–superior screw may put the main blood supply to the femoral head at risk and should be avoided.
Systemic Fibrocyte Levels and Keloid Expression of the Chemoattractant CXCL12 Are Upregulated Compared With Patients With Normal Scar
Authors: Campbell Chris A. , Burdick Marie D. , Strieter Robert M. 
Published: July 2021

Background
Fibrocytes are bone marrow mesenchymal precursors with a surface phenotype compatible with leukocytes, fibroblasts, and hematopoietic progenitors that have been shown to traffic to wound healing sites in response to described chemokine pathways. Keloids are focal fibrotic responses to cutaneous trauma characterized by disordered collagen, which may be associated with elevated systemic fibrocyte levels and/or wound bed chemokine expression.

Methods
Blood specimens from patients with longstanding keloids and those who form grossly normal scars were assayed by fluorescence activated cell sorting analysis for fibrocytes (CD45+, Col I+). The expression of the fibrocyte chemotactic cell surface marker CXCR4, intracellular markers of fibroblast differentiation (pSMAD2/3), and plasma levels of the CXCR4 cognate CXCL12 were compared. Keloid specimens and grossly normal scars were excised, and local expression of CXCL12 was assayed.

Results
Keloid-forming patients demonstrated a significantly greater number of circulating fibrocytes (17.4 × 105 cells/mL) than control patients (1.01 × 105 cells/mL, P = 0.004). The absolute number of fibrocytes expressing CXCR4 was significantly greater (P = 0.012) in keloid-forming patients. Systemic CXCL12 levels were insignificantly greater in keloid-forming patients than controls. Keloid specimens had significantly greater CXCL12 expression (529.3 pg/mL) than normal scar (undetectable).

Conclusions
Systemic fibrocyte levels and the CXCR4/CXCL12 biologic axis responsible for fibrocyte trafficking to areas of regional fibrosis were both upregulated in patients who form keloids compared with controls. Keloids persistently expressed CXLC12, which serves both as the main chemoattractant for fibrocytes and a downstream mediator for local inflammation, suggesting a role for this biologic axis in keloid formation and possibly recurrence.
Antifungal alternation can be beneficial for durability but at the cost of generalist resistance
Authors: Ballu Agathe , Despréaux Philomène , Duplaix Clémentine , Dérédec Anne , Carpentier Florence , Walker Anne-Sophie 
Published: July 2021

AbstractThe evolution of resistance to pesticides is a major burden in agriculture. Resistance management involves maximizing selection pressure heterogeneity, particularly by combining active ingredients with different modes of action. We tested the hypothesis that alternation may delay the build-up of resistance not only by spreading selection pressure over longer periods, but also by decreasing the rate of evolution of resistance to alternated fungicides, by applying an experimental evolution approach to the economically important crop pathogenZymoseptoria tritici. Our results show that alternation is either neutral or slows the overall resistance evolution rate, relative to continuous fungicide use, but results in higher levels of generalism in evolved lines. We demonstrate that the nature of the fungicides, and therefore their relative intrinsic risk of resistance may underly this trade-off, more so than the number of fungicides and the rhythm of alternation. This trade-off is also dynamic over the course of resistance evolution. These findings open up new possibilities for tailoring resistance management effectively while optimizing interplay between alternation components.
Molecular Mechanisms for Frequency Specificity in aDrosophilaHearing Organ
Authors: Hu Yufei , Jia Yinjun , Deng Tuantuan , Liu Ting , Zhang Wei 
Published: July 2021

AbstractDiscrimination for sound frequency is essential for auditory communications in animals. Here, by combiningin vivocalcium imaging and behavioral assay, we found thatDrosophilalarvae can sense a wide range of sound frequency and the behavioral specificity is mediated with the selectivity of the lch5 chordotonal organ neurons to sounds that forms a combinatorial coding of frequency. We also disclosed that Brivido1 (Brv1) and Piezo-like (Pzl), each expresses in a subset of lch5 neurons and mediate hearing sensation to certain frequency ranges. Intriguingly, mouse Piezo2 can rescuepzl-mutant’s phenotypes, suggesting a conserved role of the Piezo family proteins in high-frequency hearing.
PPARdelta signaling activation improves metabolic and contractile maturation of human pluripotent stem cell-derived cardiomyocytes
Authors: Wickramasinghe Nadeera M. , Sachs David , Shewale Bhavana , Gonzalez David M. , Dhanan-Krishnan Priyanka , Torre Denis , LaMarca Elizabeth , Raimo Serena , Dariolli Rafael , Serasinghe Madhavika N. , Mayourian Joshua , Sebra Robert , Beaumont Kristin , Iyengar Ravi , French Deborah L. , Hansen Arne , Eschenhagen Thomas , Chipuk Jerry E. , Sobie Eric A. , Jacobs Adam , Akbarian Schahram , Ischiropoulos Harry , Ma’ayan Avi , Houten Sander M. , Costa Kevin , Dubois Nicole C. 
Published: July 2021

SUMMARYPluripotent stem cell-derived cardiomyocytes (PSC-CMs) provide an unprecedented opportunity to study human heart development and disease. A major caveat however is that they remain functionally and structurally immature in culture, limiting their potential for disease modeling and regenerative approaches. Here, we address the question of how different metabolic pathways can be modulated in order to induce efficient hPSC-CM maturation. We show that PPAR signaling acts in an isoform-specific manner to balance glycolysis and fatty acid oxidation (FAO). PPARD activation or inhibition results in efficient respective up- or down-regulation of the gene regulatory networks underlying FAO in hPSC-CMs. PPARD induction further increases mitochondrial and peroxisome content, enhances mitochondrial cristae formation and augments FAO flux. Lastly PPARD activation results in enhanced myofibril organization and improved contractility. Transient lactate exposure, commonly used in hPSC-CM purification protocols, induces an independent program of cardiac maturation, but when combined with PPARD activation equally results in a metabolic switch to FAO. In summary, we identify multiple axes of metabolic modifications of hPSC-CMs and a role for PPARD signaling in inducing the metabolic switch to FAO in hPSC-CMs. Our findings provide new and easily implemented opportunities to generate mature hPSC-CMs for disease modeling and regenerative therapy.
Critical Assessment of Metagenome Interpretation - the second round of challenges
Authors: Meyer F. , Fritz A. , Deng Z.-L. , Koslicki D. , Gurevich A. , Robertson G. , Alser M. , Antipov D. , Beghini F. , Bertrand D. , Brito J. J. , Brown C.T. , Buchmann J. , Buluç A. , Chen B. , Chikhi R. , Clausen P. T. , Cristian A. , Dabrowski P. W. , Darling A. E. , Egan R. , Eskin E. , Georganas E. , Goltsman E. , Gray M. A. , Hansen L. H. , Hofmeyr S. , Huang P. , Irber L. , Jia H. , Jørgensen T. S. , Kieser S. D. , Klemetsen T. , Kola A. , Kolmogorov M. , Korobeynikov A. , Kwan J. , LaPierre N. , Lemaitre C. , Li C. , Limasset A. , Malcher-Miranda F. , Mangul S. , Marcelino V. R. , Marchet C. , Marijon P. , Meleshko D. , Mende D. R. , Milanese A. , Nagarajan N. , Nissen J. , Nurk S. , Oliker L. , Paoli L. , Peterlongo P. , Piro V. C. , Porter J. S. , Rasmussen S. , Rees E. R. , Reinert K. , Renard B. , Robertsen E. M. , Rosen G. L. , Ruscheweyh H.-J. , Sarwal V. , Segata N. , Seiler E. , Shi L. , Sun F. , Sunagawa S. , Sørensen S. J. , Thomas A. , Tong C. , Trajkovski M. , Tremblay J. , Uritskiy G. , Vicedomini R. , Wang Zi. , Wang Zhe. , Wang Zho. , Warren A. , Willassen N. P. , Yelick K. , You R. , Zeller G. , Zhao Z. , Zhu S. , Zhu J. , Garrido-Oter R. , Gastmeier P. , Hacquard S. , Häußler S. , Khaledi A. , Maechler F. , Mesny F. , Radutoiu S. , Schulze-Lefert P. , Smit N. , Strowig T. , Bremges A. , Sczyrba A. , McHardy A. C. 
Published: July 2021

AbstractEvaluating metagenomic software is key for optimizing metagenome interpretation and focus of the community-driven initiative for the Critical Assessment of Metagenome Interpretation (CAMI). In its second challenge, CAMI engaged the community to assess their methods on realistic and complex metagenomic datasets with long and short reads, created from ∼1,700 novel and known microbial genomes, as well as ∼600 novel plasmids and viruses. Altogether 5,002 results by 76 program versions were analyzed, representing a 22x increase in results.Substantial improvements were seen in metagenome assembly, some due to using long-read data. The presence of related strains still was challenging for assembly and genome binning, as was assembly quality for the latter. Taxon profilers demonstrated a marked maturation, with taxon profilers and binners excelling at higher bacterial taxonomic ranks, but underperforming for viruses and archaea. Assessment of clinical pathogen detection techniques revealed a need to improve reproducibility. Analysis of program runtimes and memory usage identified highly efficient programs, including some top performers with other metrics. The CAMI II results identify current challenges, but also guide researchers in selecting methods for specific analyses.
RNA uridyl transferases TUT4/7 differentially regulate miRNA variants depending on the cancer cell-type
Authors: Medhi Ragini , Price Jonathan , Furlan Giulia , Gorges Beronia , Sapetschnig Alexandra , Miska Eric A. 
Published: July 2021

SUMMARYThe human terminal uridyl transferases TUT4 and TUT7 (TUT4/7) catalyse additions of uridines at the 3′ end of RNAs such as the precursors of the tumour suppressor miRNA let-7, upon recruitment by the oncoprotein LIN28A. Consequently, let-7 family miRNAs are downregulated. Disruption of this TUT4/7 activity inhibits tumorigenesis and hence targeting TUT4/7 can be a potential anti-cancer therapy. In this study, we investigate TUT4/7-mediated RNA regulation in two cancer cell lines by establishing catalytic knockout models. Upon TUT4/7 mutation, we observe a significant reduction in miRNA uridylation, which results in defects in cancer cell properties such as cell proliferation and migration. With the loss of TUT4/7-mediated miRNA uridylation, the uridylated miRNA variants are replaced by adenylated isomiRs. Changes in miRNA modification profiles are accompanied by deregulation of expression levels in specific cases. Unlike let-7s, most miRNAs do not depend on LIN28A for TUT4/7-mediated regulation. Additionally, we identify TUT4/7-regulated cell-type-specific miRNA clusters and deregulation in their corresponding mRNA targets. Expression levels of miR-200c-3p and miR-141-3p are regulated by TUT4/7 in a cancer cell type specific manner. Subsequently, BCL2 which is a well-established target of miR-200c is upregulated. Therefore, TUT4/7 loss triggers deregulation of miRNA-mRNA networks in a cell-type-specific manner. Understanding of the underlying biology of such cell-type-specific deregulation will be key when targeting TUT4/7 for cancer therapy.Graphical AbstractHighlights⍰ TUT4/7 catalyse 3′ uridylation of most miRNAs⍰ Loss of uridylated isomiRs leads to the gain of adenylated isomiRs⍰ TUT4/7-mediated miRNA deregulation and miRNA-mRNA interactions are specific to the cell line type⍰ Loss of TUT4/7-mediated RNA uridylation inhibits cancer cell function
Custom-made design of metabolite composition inN. benthamianaleaves using CRISPR activators
Authors: Selma S , Sanmartín N , Espinosa-Ruiz A , Gianoglio S , Lopez-Gresa MP , Vázquez-Vilar M , Flors V , Granell A , Orzaez D 
Published: July 2021

AbstractTranscriptional regulators based on CRISPR architecture expand our ability of reprogramming endogenous gene expression in plants. One of their potential applications is the customization of plant metabolome through the activation of selected enzymes in a given metabolic pathway. Using the previously described multiplexable CRISPR activator dCasEV2.1, we assayed the selective enrichment inNicotiana benthamianaleaves of four different flavonoids, namely naringenin, eriodictyol, kaempferol and quercetin. After careful selection of target genes and guide RNAs combinations, we created successful activation programs for each of the four metabolites, each program activating between three and seven genes, and with individual gene activation levels ranging from 4- to 1500-fold. Metabolic analysis of the flavonoid profiles of each multigene activation program showed a sharp and selective enrichment of the intended metabolites and their glycosylated derivatives. Remarkably, principal component analysis of untargeted metabolic profiles clearly separated samples according to their activation treatment, and hierarchical clustering separated the samples in five groups, corresponding to the expected four highly enriched metabolite groups, plus an un-activated control. These results demonstrate that dCasEV2.1 is a powerful tool for re-routing metabolic fluxes towards the accumulation of metabolites of interest, opening the door for custom-made design of metabolic contents in plants.
Genome mosaicism in field strains of Mycoplasma bovis as footprints of in-host horizontal chromosomal transfer
Authors: García-Galán Ana , Baranowski Eric , Hygonenq Marie-Claude , Walch Mathilda , Croville Guillaume , Citti Christine , De la Fe Christian , Nouvel Laurent-Xavier 
Published: July 2021

ABSTRACTHorizontal gene transfer was long thought to be marginal in Mollicutes, but the capacity of some of these wall-less bacteria to exchange large chromosomal regions has been recently documented. Mycoplasma chromosomal transfer (MCT) is an unconventional mechanism that relies on the presence of a functional integrative conjugative element (ICE) in at least one partner and involves the horizontal acquisition of small and large chromosomal fragments from any part of the donor genome, which results in progenies composed of an infinitive variety of mosaic genomes. The present study focuses on Mycoplasma bovis, an important pathogen of cattle responsible for major economic losses worldwide. By combining phylogenetic tree reconstructions and detailed comparative genome analyses of 36 isolates collected in Spain (2016-2018) we confirmed the mosaic nature of 16 field isolates and mapped chromosomal transfers exchanged between their hypothetical ancestors. This study provides evidence that MCT can take place in the field, most likely during co-infections by multiple strains. Because mobile genetic elements (MGEs) are classical contributors of genome plasticity, the presence of phages, insertion sequences (ISs) and ICEs was also investigated. Data revealed that these elements are widespread within the M. bovis species and evidenced classical horizontal transfer of phages and ICEs in addition to MCT. These events contribute to wide-genome diversity and reorganization within this species and may have a tremendous impact on diagnostic and disease control.IMPORTANCEMycoplasma bovis is a major pathogen of cattle with significant detrimental economic and animal welfare on cattle rearing worldwide. Understanding the evolution and the adaptative potential of pathogenic mycoplasma species in the natural host is essential to combating them. In this study, we documented the occurrence of mycoplasma chromosomal transfer, an atypical mechanism of horizontal gene transfer, in field isolates of M. bovis that provide new insights into the evolution of this pathogenic species in their natural host. Despite these events are expected to occur at low frequency, their impact is accountable for genome-wide variety and reorganization within M. bovis species, which may compromise both diagnostic and disease control.