bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beyond Gender Identity Disorder Diagnoses Codes
Authors: Jasuja Guneet K. , de Groot Alexander , Quinn Emily K. , Ameli Omid , Hughto Jaclyn M.W. , Dunbar Michael , Deutsch Madeline , Streed Carl G. , Paasche-Orlow Michael K. , Wolfe Hill L. , Rose Adam J. 
Published: September 2020

Background:
Large administrative databases often do not capture gender identity data, limiting researchers’ ability to identify transgender people and complicating the study of this population.

Objective:
The objective of this study was to develop methods for identifying transgender people in a large, national dataset for insured adults.

Research Design:
This was a retrospective analysis of administrative claims data. After using gender identity disorder (GID) diagnoses codes, the current method for identifying transgender people in administrative data, we used the following 2 strategies to improve the accuracy of identifying transgender people that involved: (1) Endocrine Disorder Not Otherwise Specified (Endo NOS) codes and a transgender-related procedure code; or (2) Receipt of sex hormones not associated with the sex recorded in the patient’s chart (sex-discordant hormone therapy) and an Endo NOS code or transgender-related procedure code.

Subjects:
Seventy-four million adults 18 years and above enrolled at some point in commercial or Medicare Advantage plans from 2006 through 2017.

Results:
We identified 27,227 unique transgender people overall; 18,785 (69%) were identified using GID codes alone. Using Endo NOS with a transgender-related procedure code, and sex-discordant hormone therapy with either Endo NOS or transgender-related procedure code, we added 4391 (16%) and 4051 (15%) transgender people, respectively. Of the 27,227 transgender people in our cohort, 8694 (32%) were transmasculine, 3959 (15%) were transfeminine, and 14,574 (54%) could not be classified.

Conclusion:
In the absence of gender identity data, additional data elements beyond GID codes improves the identification of transgender people in large, administrative claims databases.
Comparison of Assays for the Diagnosis of Mycoplasma genitalium and Macrolide Resistance Mutations in Self-Collected Vaginal Swabs and Urine
Authors: Chernesky Max , Jang Dan , Martin Irene , Speicher David J. , Clavio Avery , Lidder Ravinder , Ratnam Sam , Smieja Marek , Arias Manuel , Shah Anika 
Published: September 2020

Background
The objective was to compare commercial assays on clinical specimens for Mycoplasma genitalium (MG) detection and macrolide resistance mutation (MRM) frequency.

Methods
Three self-collected vaginal swabs (VS) and a first-void urine (FVU) from 300 consented women were tested by Aptima MG (AMG), ResistancePlus MG (RPMG) and Seeplex STD6 ACE (STD6) for detection of MG. Aptima MG and STD6 MG positives were tested for MRM using MG 23S rRNA polymerase chain reaction with Sanger sequencing (23SMGSS) compared with MRM determination in the RPMG assay. Unique AMG positives were tested with confirmatory Aptima assays.

Results

M. genitalium prevalence ranged from 7.1% to 19.7%, influenced by the assay used and the specimen tested. Overall agreements for MG detection were 96.3% (κ = 0.91) for VS and 93.3% (κ = 0.72) for FVU between AMG and RPMG with lower agreements with STD6. Using a rotating reference standard, sensitivities on VS and FVU were 100% and 100% for AMG, 100% and 83.3% for RPMG, and 54.2% and 48.4% for STD6. Specificities were high for RPMG and STD6 and AMG detected extra positives, most of which were confirmed. Macrolide resistance mutation frequency rates testing VS and FVU were 50% (24/48) and 58.1% (18/31) by RPMG compared with 52.5% (31/59) and 23.5% (12/51) by 23SMGSS. MRM overall agreements between RPMG and 23SMGSS were 73.2% (κ = 0.41) for VS and 76.0% (κ = 0.52) for FVU.

Conclusions
Aptima MG detected more cases of MG infections. ResistancePlus MG detection was more effective on VS than on FVU. Seeplex STD6 ACE performance was inferior. The MRM detection component of RPMG agreed with results from 23SMGSS most of the time.
Prospective study of short-term quality-of-life after traumatic rib fractures
Authors: Choi Jeff , Khan Suleman , Hakes Nicholas A. , Carlos Garrison , Seltzer Ryan , Jaramillo Joshua D. , Spain David A. 
Published: September 2020

BACKGROUND
Postdischarge convalescence after traumatic rib fractures remains unclear. We hypothesized that patients with rib fractures, even as an isolated injury, have associated poor quality of life (QoL) after discharge.

METHODS
We prospectively enrolled adult patients at our level I trauma center with rib fractures between July 2019 and January 2020. We assessed QoL at 1 and 3 months after discharge using the Trauma-specific Quality-of-Life (T-QoL; 43-question survey evaluating five QoL domains on a 4-point Likert scale, where 4 indicates optimal and 1, worst QoL) and supplementary questionnaires. We used generalized estimating equations to assess T-QoL score trends over time and effect of age, sex, injury pattern, self-perceived injury severity, and Injury Severity Score.

RESULTS
We enrolled 139 patients (108 completed the first and 93 completed both surveys). Three months after discharge, 33% of patients were not working at preinjury capacity, and 7% were still using opioid analgesia. Suffering rib fractures mostly impacted recovery and resilience (T-QoL score, mean [robust standard error] at 1 month, 2.7 [0.1]; 3 months, 3.0[0.1]) and physical well-being domains (1 month, 2.5 [0.1]; 3 months, 2.9[0.1]). Quality of life improved over time across all domains. Compared with patients who perceived their injuries as mild/moderate, patients who perceived their injuries as severe/very severe reported worse T-QoL scores across all domains. In contrast, Injury Severity Score did not affect QoL. Patients 65 years or older (−0.6 [0.1]) and women (−0.6 [0.2]) reported worse functional engagement compared with those 65 years or older and men, respectively.

CONCLUSION
We found that patients with traumatic rib fractures experience suboptimal QoL after discharge. Quality of life improved over time, but even 3 months after discharge, patients reported challenges performing activities of daily living, slower-than-expected recovery, and not returning to work at preinjury capacity. Perception of injury severity had a large effect on QoL. Patients with rib fractures may benefit from close short-term follow-up.

LEVEL OF EVIDENCE
Prognostic and epidemiological, level III.
The management of occult hemothorax in adults with thoracic trauma: A systematic review and meta-analysis
Authors: Gilbert Richard W. , Fontebasso Adam M. , Park Lily , Tran Alexandre , Lampron Jacinthe 
Published: September 2020

BACKGROUND
Hemothorax is a common sequelae following thoracic trauma and is associated with significant morbidity and mortality. Current guidelines recommend all traumatic hemothoraces be considered for drainage with tube thoracostomy (TT), regardless of size. With increasing use of computed tomography, smaller hemothoraces not seen on x-ray (defined as an occult hemothorax) are frequently detected.

METHODS
This systematic review was performed to gather data on patients with occult hemothorax managed with TT or without TT (termed expectant management [EM]). MEDLINE, EMBASE, and Cochrane databases from inception to October 2019 were searched for relevant articles. The primary outcome was rates of failure of expectant (conservative) management. Secondary outcomes of interest included predictors of TT insertion, predictors of failure of EM, and morbidity and mortality in patients with occult hemothorax.

RESULTS
We screened 1,329 abstracts from which 6 articles reporting 1,405 patients with occult hemothorax were included. Of these patients, 601 (43.68%) were managed initially with TT, and 802 (56.32%) were managed expectantly. Of the 802 patients managed expectantly, 212 failed conservative management and underwent TT insertion (23.1% pooled failure rate estimate [95% confidence interval, 17.1–29.1%]). The presence of concomitant pneumothorax predicted upfront TT insertion. Of the patients who failed EM, the need for mechanical ventilation and the presence of a large hemothorax predicted failure. Mortality was similar in both groups.

CONCLUSIONS
Conservative treatment of occult hemothorax fails in 23.1% of patients. The presence of hemothorax greater than 300 mL and the need for mechanical ventilation predicted failure of conservative treatment and the need for TT. There was no difference in mortality between EM and TT cohorts. These data suggest that it may be possible to safely observe patients with occult hemothoraces less than 300 mL (1.5 cm pleural stripe) secondary to blunt trauma without upfront TT insertion.

LEVEL OF EVIDENCE
Systematic review and meta-analysis, level III.
Plasmin thrombelastography rapidly identifies trauma patients at risk for massive transfusion, mortality, and hyperfibrinolysis: A diagnostic tool to resolve an international debate on tranexamic acid?
Authors: Barrett Christopher D. , Moore Hunter B. , Vigneshwar Navin , Dhara Sanjeev , Chandler James , Chapman Michael P. , Sauaia Angela , Moore Ernest E. , Yaffe Michael B. 
Published: September 2020

BACKGROUND
Trauma patients with hyperfibrinolysis and depletion of fibrinolytic inhibitors (DFIs) measured by thrombelastography (TEG) gain clot strength with TXA, but TEG results take nearly an hour. We aimed to develop an assay, plasmin TEG (P-TEG), to more expeditiously stratify risk for massive transfusion (MT), mortality, and hyperfibrinolysis.

METHODS
Trauma patients (N = 148) were assessed using TEG assays without exogenous additives (rapid/native), with exogenous plasmin (P-TEG) or tissue plasminogen activator (tPA TEG). The plasmin dose used does not effect healthy-control clot lysis 30 minutes after maximum amplitude (LY30) but causes shortened reaction time (R time) relative to native TEG (P-TEG R time < native TEG R time considered P-TEG negative). If P-TEG R time is greater than or equal to native TEG R time, the patient was considered P-TEG positive. Each assay's ability to predict MT, mortality, and (risk for) hyperfibrinolysis was determined. χ2 and Mann-Whitney U tests were used to compare categorical and continuous variables, respectively. Results were reported as median ± interquartile range or n (%).

RESULTS
Plasmin TEG provided results faster than all other assays (4.7 ± 2.5–9.1 minutes), approximately 11-fold faster than rapid-TEG (rTEG) LY30 (54.2 ± 51.1–58.1 minutes; p < 0.001). Plasmin TEG–positive patients had greater than fourfold higher MT rate (30% vs. 7%; p = 0.0015) with an area under the receiver operating characteristic curve of 0.686 (p = 0.028), greater than fourfold higher 24-hour mortality (33.3% vs. 7.8%; p = 0.0177), greater than twofold higher 30-day mortality (35% vs. 16.4%; p = 0.0483), higher rates of DFI (55% vs. 18%; p < 0.001), and a trend toward elevated D-dimer (19.9 vs. 3.3 μg/mL; p = 0.14). Plasmin TEG was associated with hyperfibrinolysis on rTEG LY30 at the 7.6% threshold (p = 0.04) but not the 3% threshold (p = 0.40). Plasmin TEG performed best in relation to DFI, with a positive predictive value of 58% and negative predictive value of 81%. When combined with tPA TEG time to maximum amplitude, P-TEG outperformed rTEG LY30 for predicting MT (area under the receiver operating characteristic curve, 0.811 vs. 0.708).

CONCLUSION
Within 5 minutes, P-TEG can stratify patients at highest risk for MT, mortality, and risk for hyperfibrinolysis. In composite with tPA TEG time to maximum amplitude, P-TEG outperforms rTEG LY30 for predicting MT and does so four times faster (12.7 vs. 54.1 minutes). The rapid results of P-TEG may be useful for those who practice selective TXA administration to maximize TXA's time-dependent efficacy.

LEVEL OF EVIDENCE
Diagnostic test, level V.
NLRP3 inflammasome inhibition rescues Hutchinson-Gilford Progeria cellular phenotype and extend longevity of an animal model
Authors: Alcocer-Gómez Elísabet , Castejón-Vega Beatriz , Nuñez-Vasco Jéssica , Lendines-Cordero Débora , Navarro-Pando José M. , Cordero Mario D. 
Published: September 2020

AbstractInflammation is a hallmark of aging and accelerated aging syndromes. In this context, inflammation has been associated to the pathophysiology of Hutchinson–Gilford progeria syndrome (HGPS). In this study, we report that progeroid skin fibroblasts and animal models present an hyperactivation of the NLRP3-inflammasome complex. High expression of NLRP3 and caspase 1 was also observed in skin fibroblasts from HGPS associated to the nuclei morphology. Lymphoblast from HGPS also showed increased basal levels of NLRP3 and caspase 1 independent to the induction from metabolic factors. Consistent with these results, Zmpste24−/−showed high expression of Nlrp3 and caspase 1 in heart, liver and kidney and reduced levels of Nlrc3, however these changes were not observed in other inflammasomes. We also show that pharmacological inhibition of NLRP3 using a direct NLRP3 inhibitor, MCC950, improved cellular phenotype, significantly extends the lifespan of these progeroid animals and reduced inflammasome-dependent inflammation. These findings suggest the NLRP3-inflammasome comples as a therapeutic approach for patients with HGPS.
Free-living marine nematodes diversity at Ponta Delgada-São Miguel (Azores archipelago, North-East Atlantic Ocean): first results from shallow soft-bottom habitats
Authors: de Jesús Navarrete Alberto , Aramayo Víctor , Davidson Anitha Mary , Costa Ana Cristina 
Published: September 2020

AbstractContrasting (sand, algae, rocky-dominated, mixed) benthic habitats were sampled to characterize marine nematode diversity inhabiting surface sediments in São Miguel (Azores, North-East Atlantic Ocean) in July 2019. Nematodes were extracted from the surface layer of sediments and morphologically identified using light microscopy. Nematode taxonomy was based on living/fresh specimens) to ensure a suitable recognition of morphological traits. Our results provide a preliminary checklist of free-living marine nematode genera from 21 intertidal and sublittoral sandy beach sites along the coast of São Miguel island, Azores archipelago, Portugal. The nematode fauna was represented by 4 orders, 21 families, and 43 genera.Cyatholaimus,DesmodoraandDaptonemahad two morphospecies each. Enoplida was represented by 8 families and 13 genera, while Chromadorida by 7 families and 18 genera, the latter corresponding to the most diverse nematode group. Monhysterida had 5 families and 10 genera and Araeolaimida was represented by a single 1 family and 2 genera. The most common genera (i.e., accounting for 75% of all organisms) includedAdoncholaimus(most abundant genus, 32 specimens),Axonolaimus(18),Cyatholaimus(17),Enoploides(13),Rhabdocoma, andAcanthopharynx(11).ViscosiaandEnoplolaimuswere represented by 7 specimens, whilstHalalaimus,Desmoscolex,Monophostia,Daptonema, andTheristusobtained only 6 each. The dominant nematode taxa of São Miguel island have been commonly previously reported in other coastal habitats including sandy beaches. They can be considered typical meiofaunal components of intertidal sandy beaches. Many of the nematode morphotypes found in São Miguel island could represent new species to science. As far as we know, this is the first report on free-living nematodes for São Miguel Island and for marine shallow water in the Azores. Our findings will serve as an import baseline for future research aiming to improve our understating of nematode communities in volcanic islands such as São Miguel in the Azores archipelago.
Nanobody-mediated control of gene expression and epigenetic memory
Authors: Van Mike V. , Fujimori Taihei , Bintu Lacramioara 
Published: September 2020

AbstractTargeting chromatin regulators to specific genomic locations for gene control is emerging as a powerful method in basic research and synthetic biology. However, many chromatin regulators are large, making them difficult to deliver and combine in mammalian cells. Here, we developed a new strategy for gene control using small nanobodies that bind and recruit endogenous chromatin regulators to a gene. We show that an antiGFP nanobody can be used to simultaneously visualize GFP-tagged chromatin regulators and control gene expression, and that nanobodies against HP1 and DNMT1 can silence a reporter gene. Moreover, combining nanobodies together or with other regulators, such as DNMT3A or KRAB, can enhance silencing speed and epigenetic memory. Finally, we use the slow silencing speed and high memory of antiDNMT1 to build a signal duration timer and recorder. These results set the basis for using nanobodies against chromatin regulators for controlling gene expression and epigenetic memory.
Asthma-associated variants induceIL33differential expression through a novel regulatory region
Authors: Aneas Ivy , Decker Donna C. , Howard Chanie L. , Sobreira Débora R. , Sakabe Noboru J. , Blaine Kelly M. , Stein Michelle M. , Hrusch Cara L. , Montefiori Lindsey E. , Tena Juan , Magnaye Kevin M. , Clay Selene M. , Gern James E. , Jackson Daniel J. , Altman Matthew C. , Naureckas Edward T. , Hogarth Douglas K. , White Steven R. , Gomez-Skarmeta Jose Luis , Schoetler Nathan , Ober Carole , Sperling Anne I. , Nobrega Marcelo A. 
Published: September 2020

ABSTRACTGenome-wide association studies (GWAS) have implicated theIL33locus in asthma, but the underlying mechanisms remain unclear. Here, we identify a 5 kb region within the GWAS-defined segment that acts as a strong regulatory elementin vivoandin vitro.Chromatin conformation capture showed that this 5 kb region loops to theIL33promoter, potentially regulating its expression. Supporting this notion, we show that genotype at an asthma-associated SNP, rs1888909, located within the 5 kb region, is associated withIL33gene expression in human airway epithelial cells and IL-33 protein expression in human plasma, potentially through differential binding of OCT-1 (POU2F1) to the asthma-risk allele. Our data demonstrate that asthma-associated variants at theIL33locus mediate allele-specific regulatory activity andIL33expression, providing a novel mechanism through which a regulatory SNP contributes to genetic risk of asthma.
“Proliferation of DBLOX Peroxidase-Expressing Oenocytes Maintains Innate Immune Memory in Primed Mosquitoes”
Authors: Gomes Fabio M. , Tyner Miles D.W. , Barletta Ana Beatriz F. , Yenkoidiok-Douti Lampougin , Canepa Gaspar E. , Molina-Cruz Alvaro , Barillas-Mury Carolina 
Published: September 2020

AbstractImmune priming inAnopheles gambiaemosquitoes following infection withPlasmodiumparasites is mediated by the systemic release of a hemocyte differentiation factor (HDF), a complex of lipoxin A4bound to Evokin, a lipid carrier. HDF increases the proportion of circulating granulocytes and enhances mosquito cellular immunity. We found that Evokin is constitutively produced by hemocytes and fat-body cells, but expression increases in response to infection. Insects synthesize lipoxins, but lack lipoxygenases. Here, we show that the Double Peroxidase (DBLOX) enzyme, present in insects but not in vertebrates, is essential for HDF synthesis. DBLOX is highly expressed in oenocytes in the fat body tissue, and these cells proliferate in response toPlasmodiumchallenge. We provide direct evidence that modifications mediated by the histone acetyltransferase AgTip60 (AGAP01539) are essential for sustained oenocyte proliferation, HDF synthesis and immune priming. We propose that oenocytes function as a population of “memory” cells that continuously release lipoxin to orchestrate and maintain a broad, systemic and long-lasting state of enhanced immune surveillance.
Supraphysiological testosterone induces ferroptosis and activates NF-kappaB mediated immune pathways in prostate cancer through nucleophagy
Authors: Mendonca Janet , Kumar Rajendra , Owoyemi Olutosin , Boyapati Kavya , Thomas Naiju , Kanacharoen Suthicha , Coffey Max , Topiwala Deven , Gomes Carolina , Ozbek Busra , Jones Tracy , Rosen Marc , Dong Liang , Wiens Sadie , Brennen W. Nathaniel , Isaacs John , De Marzo Angelo M. , Markowski Mark , Antonarakis Emmanuel S. , Qian David , Pienta Kenneth , Pardoll Drew , Carducci Michael , Denmeade Samuel , Kachhap Sushant 
Published: September 2020

AbstractThe discovery that androgens play an important role in the progression of prostate cancer (PCa) has led to the development of androgen deprivation therapy as a first line of treatment against PCa. However, paradoxical growth inhibition has been observed, both experimentally and clinically, in a subset of PCa upon administration of supraphysiological levels of testosterone (SupraT). Here we report that SupraT activates cytoplasmic nucleic acid sensors and induces growth inhibition of SupraT-sensitive PCa cells. This is initiated by induction of two parallel autophagy-mediated processes, namely, ferritinophagy and nucleophagy. Consequently, autophagosomal DNA activates nucleic acid sensors that converge on NF-kappaB to drive immune signaling pathways. Chemokines and cytokines secreted by the tumor cells in response to SupraT results in increased migration of cytotoxic immune cells to tumor beds of animal xenografts and patient tumors. Collectively, our findings indicate that SupraT may inhibit a subset of PCa by activating nucleic acid sensors and downstream immune signaling.
Real-time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles
Authors: Lu Maolin , Uchil Pradeep D. , Li Wenwei , Zheng Desheng , Terry Daniel S. , Gorman Jason , Shi Wei , Zhang Baoshan , Zhou Tongqing , Ding Shilei , Gasser Romain , Prévost Jérémie , Beaudoin-Bussières Guillaume , Anand Sai Priya , Laumaea Annemarie , Grover Jonathan R. , Liu Lihong , Ho David D. , Mascola John R. , Finzi Andrés , Kwong Peter D. , Blanchard Scott C. , Mothes Walther 
Published: September 2020

AbstractSARS-CoV-2 spike (S) mediates entry into cells and is critical for vaccine development against COVID-19. Structural studies have revealed distinct conformations of S, but real-time information that connects these structures, is lacking. Here we apply single-molecule Förster Resonance Energy Transfer (smFRET) imaging to observe conformational dynamics of S on virus particles. Virus-associated S dynamically samples at least four distinct conformational states. In response to hACE2, S opens sequentially into the hACE2-bound S conformation through at least one on-path intermediate. Conformational preferences of convalescent plasma and antibodies suggest mechanisms of neutralization involving either competition with hACE2 for binding to RBD or allosteric interference with conformational changes required for entry. Our findings inform on mechanisms of S recognition and conformations for immunogen design.