bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and efficacy of different P2Y12 inhibitors in patients with acute coronary syndromes stratified by the PRAISE risk score: a multicentre study
Authors: Patti Giuseppe , D'Ascenzo Fabrizio , De Filippo Ovidio , Bruno Francesco , Leonardi Sergio , Chieffo Alaide , Iannaccone Mario , Liebetrau Christoph , Manzano-Fernández Sergio , Gallone Guglielmo , Omedè Pierluigi , Cerrato Enrico , Kinnaird Tim , Conrotto Federico , Piroli Francesco , Henriques Jose Paulo Simao , Wańha Wojciech , Elia Edoardo , Dominguez-Rodriguez Alberto , Raposeiras-Roubin Sergio , Abu-Assi Emad , De Ferrari Gaetano Maria ,   PRAISE Study Group
Published: January 2022

Aims

To establish the safety and efficacy of different dual antiplatelet therapy (DAPT) combinations in patients with acute coronary syndrome (ACS) according to their baseline ischaemic and bleeding risk estimated with a machine learning derived model [machine learning-based prediction of adverse events following an acute coronary syndrome (PRAISE) score].

Methods and results

Incidences of death, re-acute myocardial infarction (re-AMI), and Bleeding Academic Research Consortium 3–5 bleeding with aspirin plus different P2Y12 inhibitors (clopidogrel or potent P2Y12 inhibitors: ticagrelor or prasugrel) were appraised among patients of the PRAISE data set grouped in four subcohorts: low-to-moderate ischaemic and bleeding risk; low-to-moderate ischaemic risk and high bleeding risk; high ischaemic risk and low-to-moderate bleeding risk; and high ischaemic and bleeding risk. Hazard ratios (HRs) for the outcome measures were derived with inverse probability of treatment weighting adjustment. Among patients with low-to-moderate bleeding risk, clopidogrel was associated with higher rates of re-AMI in those at low-to-moderate ischaemic risk [HR 1.69, 95% confidence interval (CI) 1.16–2.51; P = 0.006] and increased risk of death (HR 3.2, 1.45–4.21; P = 0.003) and re-AMI (HR 2.23, 1.45–3.41; P < 0.001) in those at high ischaemic risk compared with prasugrel or ticagrelor, without a difference in the risk of major bleeding. Among patients with high bleeding risk, clopidogrel showed comparable risk of death, re-AMI, and major bleeding vs. potent P2Y12 inhibitors, regardless of the baseline ischaemic risk.

Conclusion

Among ACS patients with non-high risk of bleeding, the use of potent P2Y12 inhibitors is associated with a lower risk of death and recurrent ischaemic events, without bleeding excess. Patients deemed at high bleeding risk may instead be safely addressed to a less intensive DAPT strategy with clopidogrel.
Incidence and 1-year outcome of periprocedural myocardial infarction following cardiac surgery: are the Universal Definition and Society for Cardiovascular Angiography and Intervention criteria fit for purpose?
Authors: Hinton Jonathan , Augustine Maclyn , Gabara Lavinia , Mariathas Mark , Allan Rick , Borca Florina , Nicholas Zoe , Ikwuobe John , Gillett Neil , Kwok Chun Shing , Cook Paul , Grocott Michael P W , Mamas Mamas , Curzen Nick
Published: January 2022

OBJECTIVES

The diagnosis and clinical implications of periprocedural myocardial infarction (PPMI) following coronary artery bypass grafting (CABG) are contentious, especially the importance of PPMI in the interpretation of trial data.

METHODS

Consecutive patients admitted to a cardiothoracic critical care unit over a 6-month period following open cardiac surgery had high-sensitivity cardiac troponin I assay performed on admission and every day for 48 h, regardless of whether there was a request by the supervising clinical team. Patients were categorized as PPMI using both the Universal Definition of Myocardial Infarction (UDMI) and Society of Cardiovascular Angiography and Interventions (SCAI) criteria. Multivariable Cox regression analysis was performed to assess whether any relationships between PPMI diagnoses and 1-year mortality were independent.

RESULTS

There were 2 groups of consecutive patients: (i) after CABG (n = 245) and (ii) after non-CABG surgery (n = 243). Of the CABG patients, 20.4% met criteria for UDMI PPMI and 87.6% for SCAI PPMI. The diagnosis of UDMI PPMI was independently associated with 1-year mortality on multivariable Cox regression analysis [hazard ratio 4.16 (95% confidence interval 1.28–13.49)]. Of 243 patients who had non-CABG cardiac surgery, 11.4% met criteria for UDMI PPMI and 85.2% for SCAI PPMI but neither were associated with 1-year mortality.

CONCLUSIONS

The incidence of SCAI PPMI in a real-world cohort of cardiac surgery patients is so high as to be of limited clinical value. In contrast, a diagnosis of UDMI PPMI post-CABG is independently associated with 1-year mortality, so may have clinical (and research) utility.
The benefits and challenges of established peer support programmes for patients, informal caregivers, and healthcare providers
Authors: Joo Jin Hui , Bone Lee , Forte Joan , Kirley Erin , Lynch Thomas , Aboumatar Hanan
Published: January 2022

Purpose

Peer support programmes that provide services for various health conditions have been in existence for many years; however, there is little study of their benefits and challenges. Our goal was to explore how existing peer support programmes help patients with a variety of health conditions, the challenges that these programmes meet, and how they are addressed.

Methods

We partnered with 7 peer support programmes operating in healthcare and community settings and conducted 43 semi-structured interviews with key informants. Audiorecordings were transcribed and qualitative analysis was conducted using grounded theory methods.

Results

Peer support programmes offer informational and psychosocial support, reduce social isolation, and connect patients and caregivers to others with similar health issues. These programmes provide a supportive community of persons who have personal experience with the same health condition and who can provide practical information about self-care and guidance in navigating the health system. Peer support is viewed as different from and complementary to professional healthcare services. Existing programmes experience challenges such as matching of peer supporter and peer recipient and maintaining relationship boundaries. They have gained experience in addressing some of these challenges.

Conclusions

Peer support programmes can help persons and caregivers manage health conditions but also face challenges that need to be addressed through organizational processes. Peer support programmes have relevance for improving healthcare systems, especially given the increased focus on becoming more patient-centred. Further study of peer programmes and their relevance to improving individuals’ well-being is warranted.
Trends in the conduct and reporting of clinical prediction model development and validation: a systematic review
Authors: Yang Cynthia , Kors Jan A , Ioannou Solomon , John Luis H , Markus Aniek F , Rekkas Alexandros , de Ridder Maria A J , Seinen Tom M , Williams Ross D , Rijnbeek Peter R
Published: January 2022

Objectives

This systematic review aims to provide further insights into the conduct and reporting of clinical prediction model development and validation over time. We focus on assessing the reporting of information necessary to enable external validation by other investigators.

Materials and Methods

We searched Embase, Medline, Web-of-Science, Cochrane Library, and Google Scholar to identify studies that developed 1 or more multivariable prognostic prediction models using electronic health record (EHR) data published in the period 2009–2019.

Results

We identified 422 studies that developed a total of 579 clinical prediction models using EHR data. We observed a steep increase over the years in the number of developed models. The percentage of models externally validated in the same paper remained at around 10%. Throughout 2009–2019, for both the target population and the outcome definitions, code lists were provided for less than 20% of the models. For about half of the models that were developed using regression analysis, the final model was not completely presented.

Discussion

Overall, we observed limited improvement over time in the conduct and reporting of clinical prediction model development and validation. In particular, the prediction problem definition was often not clearly reported, and the final model was often not completely presented.

Conclusion

Improvement in the reporting of information necessary to enable external validation by other investigators is still urgently needed to increase clinical adoption of developed models.
Spinosyns Delivered in Sugar Meals to Aedes aegypti and Aedes albopictus (Diptera: Culicidae): Acute Toxicity and Subacute Effects on Survival, Fecundity, and Fertility
Authors: Alomar Abdullah A , Alto Barry W , Walker Edward D
Published: January 2022

Sugar is an essential source of nutrition for adult mosquitoes to acquire energy. Toxic sugar bait (TSB) provides a promising method for mosquito control by incorporating toxins into artificial sources of sugar (i.e., toxic baits) presented to wild populations. Spinosyns comprise a family of bacterial secondary metabolites with a unique mode of action against the insect nervous system, an appealing environmental safety profile, and potential for incorporation into sugar baits. This research evaluated acute and subacute effects of spinosad (spinosyns A and D) and spinetoram (spinosyns J and L) in sugar meals on survival, fecundity, and fertility of Aedes aegypti and Aedes albopictus. Acute toxicity of spinosyns doubled from 24 to 48 h of assessment, revealing a relatively slow and cumulative action of the formulated spinosyns. Median lethal concentrations at 48 h were lower for spinetoram than for spinosad, lower for Ae. albopictus than Ae. aegypti, and lower for males than females. When exposed to subacute LC50 concentrations of spinosad and spinetoram for 24 h, survival of males and females of both species was diminished compared with controls, fecundity of females was increased, but fertility as measured by hatch rate of eggs was decreased. The formulations may have increased the nutritive value of the sugar meals thereby boosting fecundity, while toxifying embryos, reducing fertility. The inclusion of subacute effects of spinosyns allows assessment of the broader consequences of TSB for adult mosquito control.
Racial Disparities in Medication Adherence Barriers: Pediatric Epilepsy as an Exemplar
Authors: Gutierrez-Colina Ana M , Wetter Sara E , Mara Constance A , Guilfoyle Shanna , Modi Avani C
Published: January 2022

Objective

To evaluate how racial disparities in medication adherence barriers relate to key clinical outcomes (i.e., seizure control and adherence) in pediatric epilepsy and to identify the most critical barriers in determining health outcomes in Black youth and White youth.

Methods

This observational study included a sample of youth aged 2–17 years with epilepsy obtained by combining data from four different studies. A total of 226 caregivers and 43 adolescents reported on adherence barriers. An electronic monitor was used to measure adherence to the primary antiepileptic drug. Racial disparities in individual barriers were examined. The relative importance of different types of barriers in determining clinical outcomes was evaluated in both Black and White youth.

Results

Adherence barriers, including running out of medications, access to pharmacies, competing demands, and difficulty swallowing, disproportionally affected Black children with epilepsy compared to White children. System- and community-level barriers emerged as the most important in determining seizure outcomes among Black youth. Both system- and individual-level barriers, on the other hand, were important for adherence outcomes.

Conclusions

System- and community-level barriers, as opposed to individual-level barriers, are more highly endorsed by Black families compared to White families. These barriers are also the most critical in driving seizure outcomes among Black youth. There is a critical need to shift from a primary focus on individual-level barriers to an approach that deliberately targets larger systemic barriers to reduce the existing adherence and health disparities that affect Black children with pediatric conditions.
A highly mutually inclined compact warm-Jupiter system KOI-984?
Authors: Sun L , Ioannidis P , Gu S , Schmitt J H M M , Wang X , Kouwenhoven M B N , Perdelwitz V , Flammini Dotti F , Czesla S
Published: January 2022

The discovery of a population of close-orbiting giant planets (≤ 1 au) has raised a number of questions about their origins and dynamical histories. These issues have still not been fully resolved, despite over 20 years of exoplanet detections and a large number of discovered exoplanets. In particular, it is unclear whether warm Jupiters (WJs) form in situ, or whether they migrate from further outside and are even currently migrating to form hot Jupiters. Here, we report the possible discovery and characterization of the planets in a highly mutually inclined (Imut ≃ 45°) compact two-planet system (KOI-984), in which the newly discovered warm Jupiter KOI-984c is on a 21.5-d moderately eccentric (e ≃ 0.4) orbit, in addition to a previously known 4.3-d planet candidate KOI-984b. Meanwhile, the orbital configuration of a moderately inclined (Imut ≃ 15°) low-mass (mc ≃ 24M⊕; Pb ≃ 8.6 d) perturbing planet near the 1:2 mean-motion resonance with KOI-984b could also well reproduce the observed transit-timing variations and transit-duration variations of KOI-984b. Such an eccentric WJ with a close-in sibling would pose a challenge to the proposed formation and migration mechanisms of WJs if the first scenario is supported with more evidence in the near future; this system with several other well measured inclined WJ systems (e.g. Kepler-419 and Kepler-108) may provide additional clues to the origin and dynamical histories of WJs.
A Suzaku sample of unabsorbed narrow-line and broad-line Seyfert 1 galaxies – II. Iron emission and absorption
Authors: Waddell S G H , Gallo L C
Published: January 2022

A sample of 22 narrow-line type 1 Seyfert (NLS1) and 47 broad-line type 1 Seyfert (BLS1) galaxies observed with Suzaku is used to examine the Fe K-band properties of each group. Three different models are used to examine the presence of: narrow neutral Fe K α line at $6.4{\rm \, keV}$ and ionized Fe xxv and Fe xxvi emission lines (model A); a broad emission feature at around $6{-}7{\rm \, keV}$ (model B); and an absorption edge at ${\sim}7.1{\rm \, keV}$ (model C). In all three models, the neutral Fe K α line is weaker (lower luminosity and equivalent width) in NLS1s than in BLS1s. Model (B) also finds a more significant broad component (larger equivalent width) in NLS1s than in BLS1s. The feature does not appear to be an artifact of steeper spectra in NLS1s, but rather an intrinsic property of these sources. From model (C), the optical depth of the absorption edge appears comparable between the two samples. When comparing the absorption with the emission line properties, NLS1s seem to exhibit a lower ratio of emission-to-absorption of iron than BLS1s, and have a lower value than expected based on the fluorescence yield. The observed differences may arise from different torus geometries (e.g. larger opening angle in NLS1s), and/or additional sources of Fe K emission and absorption in NLS1s beyond pure fluorescence (e.g. originating in the disc and broad-line region).
Optical line spectra of tidal disruption events from reprocessing in optically thick outflows
Authors: Parkinson Edward J , Knigge Christian , Matthews James H , Long Knox S , Higginbottom Nick , Sim Stuart A , Mangham Samuel W
Published: January 2022

A significant number of tidal disruption events (TDEs) radiate primarily at optical and ultraviolet (UV) wavelengths, with only weak soft X-ray components. One model for this optical excess proposes that thermal X-ray emission from a compact accretion disc is reprocessed to longer wavelengths by an optically thick envelope. Here, we explore this reprocessing scenario in the context of an optically thick accretion disc wind. Using state-of-the-art Monte Carlo radiative transfer and ionization software, we produce synthetic UV and optical spectra for wind and disc-hosting TDEs. Our models are inspired by observations, spanning a realistic range of accretion rates and wind kinematics. We find that such outflows can efficiently reprocess the disc emission and produce the broad Balmer and helium recombination features commonly seen in TDEs and exhibit asymmetric red wings. Moreover, the characteristic colour temperature of the reprocessed spectral energy distribution (SED) is much lower than that of the accretion disc. We show explicitly how changes in black hole mass, accretion rate, and wind properties affect the observed broad-band SED and line spectrum. In general, slower, denser winds tend to reprocess more radiation and produce stronger Balmer emission. Most of the outflows we consider are too highly ionized to produce UV absorption features, but this is sensitive to the input SED. For example, truncating the inner disc at just ≃4RISCO lowers the wind ionization state sufficiently to produce UV absorption features for sightlines looking into the wind.
Dynamic RNA Fitness Landscapes of a Group I Ribozyme during Changes to the Experimental Environment
Authors: Peri Gianluca , Gibard Clémentine , Shults Nicholas H , Crossin Kent , Hayden Eric J
Published: January 2022

Fitness landscapes of protein and RNA molecules can be studied experimentally using high-throughput techniques to measure the functional effects of numerous combinations of mutations. The rugged topography of these molecular fitness landscapes is important for understanding and predicting natural and experimental evolution. Mutational effects are also dependent upon environmental conditions, but the effects of environmental changes on fitness landscapes remains poorly understood. Here, we investigate the changes to the fitness landscape of a catalytic RNA molecule while changing a single environmental variable that is critical for RNA structure and function. Using high-throughput sequencing of in vitro selections, we mapped a fitness landscape of the Azoarcus group I ribozyme under eight different concentrations of magnesium ions (1–48 mM MgCl2). The data revealed the magnesium dependence of 16,384 mutational neighbors, and from this, we investigated the magnesium induced changes to the topography of the fitness landscape. The results showed that increasing magnesium concentration improved the relative fitness of sequences at higher mutational distances while also reducing the ruggedness of the mutational trajectories on the landscape. As a result, as magnesium concentration was increased, simulated populations evolved toward higher fitness faster. Curve-fitting of the magnesium dependence of individual ribozymes demonstrated that deep sequencing of in vitro reactions can be used to evaluate the structural stability of thousands of sequences in parallel. Overall, the results highlight how environmental changes that stabilize structures can also alter the ruggedness of fitness landscapes and alter evolutionary processes.
Control of backbone chemistry and chirality boost oligonucleotide splice switching activity
Authors: Kandasamy Pachamuthu , McClorey Graham , Shimizu Mamoru , Kothari Nayantara , Alam Rowshon , Iwamoto Naoki , Kumarasamy Jayakanthan , Bommineni Gopal R , Bezigian Adam , Chivatakarn Onanong , Butler David C D , Byrne Michael , Chwalenia Katarzyna , Davies Kay E , Desai Jigar , Shelke Juili Dilip , Durbin Ann F , Ellerington Ruth , Edwards Ben , Godfrey Jack , Hoss Andrew , Liu Fangjun , Longo Kenneth , Lu Genliang , Marappan Subramanian , Oieni Jacopo , Paik Ik-Hyeon , Estabrook Erin Purcell , Shivalila Chikdu , Tischbein Maeve , Kawamoto Tomomi , Rinaldi Carlo , Rajão-Saraiva Joana , Tripathi Snehlata , Yang Hailin , Yin Yuan , Zhao Xiansi , Zhou Cong , Zhang Jason , Apponi Luciano , Wood Matthew J A , Vargeese Chandra
Published: January 2022

Although recent regulatory approval of splice-switching oligonucleotides (SSOs) for the treatment of neuromuscular disease such as Duchenne muscular dystrophy has been an advance for the splice-switching field, current SSO chemistries have shown limited clinical benefit due to poor pharmacology. To overcome limitations of existing technologies, we engineered chimeric stereopure oligonucleotides with phosphorothioate (PS) and phosphoryl guanidine-containing (PN) backbones. We demonstrate that these chimeric stereopure oligonucleotides have markedly improved pharmacology and efficacy compared with PS-modified oligonucleotides, preventing premature death and improving median survival from 49 days to at least 280 days in a dystrophic mouse model with an aggressive phenotype. These data demonstrate that chemical optimization alone can profoundly impact oligonucleotide pharmacology and highlight the potential for continued innovation around the oligonucleotide backbone. More specifically, we conclude that chimeric stereopure oligonucleotides are a promising splice-switching modality with potential for the treatment of neuromuscular and other genetic diseases impacting difficult to reach tissues such as the skeletal muscle and heart.
POLIE suppresses telomerase-mediated telomere G-strand extension and helps ensure proper telomere C-strand synthesis in trypanosomes
Authors: Rabbani M A G , Tonini Maiko Luis , Afrin Marjia , Li Bibo
Published: January 2022

Trypanosoma brucei causes human African trypanosomiasis and sequentially expresses distinct VSGs, its major surface antigen, to achieve host immune evasion. VSGs are monoallelically expressed from subtelomeric loci, and telomere proteins regulate VSG monoallelic expression and VSG switching. T. brucei telomerase is essential for telomere maintenance, but no regulators of telomerase have been identified. T. brucei appears to lack OB fold-containing telomere-specific ssDNA binding factors that are critical for coordinating telomere G- and C-strand syntheses in higher eukaryotes. We identify POLIE as a telomere protein essential for telomere integrity. POLIE-depleted cells have more frequent VSG gene conversion-mediated VSG switching and an increased amount of telomeric circles (T-circles), indicating that POLIE suppresses DNA recombination at the telomere/subtelomere. POLIE-depletion elongates telomere 3′ overhangs dramatically, indicating that POLIE is essential for coordinating DNA syntheses of the two telomere strands. POLIE depletion increases the level of telomerase-dependent telomere G-strand extension, identifying POLIE as the first T. brucei telomere protein that suppresses telomerase. Furthermore, depletion of POLIE results in an elevated telomeric C-circle level, suggesting that the telomere C-strand experiences replication stress and that POLIE may promote telomere C-strand synthesis. Therefore, T. brucei uses a novel mechanism to coordinate the telomere G- and C-strand DNA syntheses.
The second polar body contributes to the fate asymmetry in the mouse embryo
Authors: Jin Hongbin , Han Yang , Wang Huasong , Li J Xiao He , Shen Weimin , Zhang Lin , Chen Luxi , Jia Shunji , Yuan Ping , Chen Hui , Meng Anming
Published: January 2022

abstract

The polar bodies (PBs) are extruded microcells during oocyte meiosis and generally regarded as inessentials for embryonic development. Therefore, PBs have been widely used as important materials for pre-implantation genetic diagnosis in human. Here we report that the second PB (PB2) in the mouse zygote may play roles in cell-fate specification and post-implantation development. A subset of mRNAs encoding pluripotency-related factors are enriched in PB2. Nascent proteins may be synthesized in PB2 after fertilization and transport from PB2 to the zygote before the two-cell stage. The PB2-attached blastomere (pbB) at the two-cell stage, compared to the other blastomere (npbB), likely contributes more descendants to the inner cell mass (ICM) lineage in the blastocyst. Removal of PB2 from the zygote or transient blockage of material exchange between PB2 and the zygote by nocodazole treatment appears to cause a loss of the ICM fate bias of pbB. PB2 removal or nocodazole treatment also results in abnormal post-implantation development. Injection of PB2 lysate into pbB of PB2-removed two-cell-stage embryos may reset the cell-fate preference and rescue post-implantation development. Our data collectively suggest that PB2 would demarcate the earliest cell-fate asymmetry of the mouse zygote and be required for post-implantation development.
Long-term Outcomes with Nivolumab as First-line Treatment in Recurrent or Metastatic Head and Neck Cancer: Subgroup Analysis of CheckMate 141
Authors: Gillison Maura L , Blumenschein George , Fayette Jerome , Guigay Joel , Colevas A Dimitrios , Licitra Lisa , Harrington Kevin J , Kasper Stefan , Vokes Everett E , Even Caroline , Worden Francis , Saba Nabil F , Iglesias Docampo Lara Carmen , Haddad Robert , Rordorf Tamara , Kiyota Naomi , Tahara Makoto , Jayaprakash Vijayvel , Wei Li , Ferris Robert L
Published: January 2022

In the randomized, phase 3 CheckMate 141 trial, nivolumab significantly improved overall survival (OS) versus investigator’s choice (IC) of chemotherapy at primary analysis among 361 patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) post-platinum therapy. Nivolumab versus IC as first-line treatment also improved OS among patients with R/M SCCHN who progressed on platinum therapy for locally advanced disease in the adjuvant or primary setting at 1-year follow-up. In the present long-term follow-up analysis of patients receiving first-line treatment, OS benefit with nivolumab (n = 50) versus IC (n = 26) was maintained (median: 7.7 months versus 3.3 months; hazard ratio: 0.56; 95% confidence interval, 0.34-0.94) at 2 years. No new safety signals were identified. In summary, this long-term 2-year analysis of CheckMate 141 supports the use of nivolumab as a first-line treatment for patients with platinum-refractory R/M SCCHN.
Structure of the super-Eddington outflow and its impact on the cosmological scale
Authors: Botella Ignacio , Mineshige Shin , Kitaki Takaaki , Ohsuga Ken , Kawashima Tomohisa
Published: January 2022

It is one of the biggest issues in black hole (BH) astrophysics how to evaluate BH feedback to its environments precisely. Aiming at studying the unique gas dynamics of super-Eddington flow around supermassive black hole (SMBH) seeds at high redshift, we carried out axisymmetric two-dimensional radiation hydrodynamic simulations using a nested simulation-box method. Here we divide the simulation box into an inner zone at (2–3 × 103)rSch (with rSch being the Schwarzschild radius) and an outer zone at (2 × 103–3 × 106)rSch, with smooth connection of the physical quantities, such as gas density, velocity, and radiation energy. We start the calculation by injecting mass through the outer boundary of the inner zone at a constant rate of $\dot{M}_{\rm {inj}}=10^3L_{\rm {Edd}}/c^2$, where LEdd is the Eddington luminosity and c is the speed of light. A powerful outflow is generated in the innermost region and it propagates from the inner zone to the outer zone. The outflows are characterized by a velocity of 0.02c (0.7c) and density of 10−17 (10−19) g cm−3 for near the edge-on (face-on) direction. The outflow is gradually accelerated as it travels by accepting radiation-pressure force. The final mass outflow rate at the outermost boundary is $\dot{M}_{\rm {out}}\sim 0.3 \times \dot{M}_{\rm {inj}}$. By extrapolating the outflow structure to a further larger scale, we find that the momentum and energy fluxes at r ∼ 0.1 pc are ∼10–100 LEdd/c and ∼0.1–10 LEdd, respectively. Moreover, we find that the impacts are highly anisotropic, in the sense that larger impacts occur towards the face-on direction than in the edge-on direction. These results indicate that the BH feedback will work more efficiently on the interstellar medium than assumed in the cosmological simulations.
CFI 25 Subunit of Cleavage Factor I is Important for Maintaining the Diversity of 3ʹ UTR Lengths in Arabidopsis thaliana (L.) Heynh.
Authors: Zhang Xiaojuan , Nomoto Mika , Garcia-León Marta , Takahashi Naoki , Kato Mariko , Yura Kei , Umeda Masaaki , Rubio Vicente , Tada Yasuomi , Furumoto Tsuyoshi , Aoyama Takashi , Tsuge Tomohiko
Published: January 2022

Cleavage and polyadenylation at the 3ʹ end of the pre-mRNA is essential for mRNA function, by regulating its translatability, stability and translocation to the cytoplasm. Cleavage factor I (CFI) is a multi-subunit component of the pre-mRNA 3ʹ end processing machinery in eukaryotes. Here, we report that plant CFI 25 subunit of CFI plays an important role in maintaining the diversity of the 3ʹ ends of mRNA. The genome of Arabidopsis thaliana (L.) Heynh. contained four genes encoding three putative CFI subunits (AtCFI 25, AtCFI 59 and AtCFI 68), orthologous to the mammalian CFI subunits. There were two CFI 25 paralogs (AtCFI 25a and AtCFI 25b) that shared homology with human CFI 25. Two null alleles of AtCFI 25a displayed smaller rosette leaves, longer stigmatic papilla, smaller anther, earlier flowering and lower fertility compared to wild-type plants. Null alleles of AtCFI 25b, as well as, plants ectopically expressing full-length cDNA of AtCFI 25a, displayed no obvious morphological defects. AtCFI 25a was shown to interact with AtCFI 25b, AtCFI 68 and itself, suggesting various forms of CFI in plants. Furthermore, we show that AtCFI 25a function was essential for maintaining proper diversity of the 3ʹ end lengths of transcripts coding for CFI subunits, suggesting a self-regulation of the CFI machinery in plants. AtCFI 25a was also important to maintain 3ʹ ends for other genes to different extent. Collectively, AtCFI 25a, but not AtCFI 25b, seemed to play important roles during Arabidopsis development by maintaining proper diversity of the 3ʹ UTR lengths.
Injection into the Space of Okada During Transforaminal Epidural Steroid Injections
Authors: Tiegs-Heiden Christin A , Madhavan Ajay A , Diehn Felix E , Lehman Vance T , Murthy Naveen S
Published: January 2022

Objective

Ensuring medication delivery to the epidural space is crucial for effective transforaminal epidural steroid injections. Epidural needle placement is determined by injecting a small amount of contrast at the final needle position. The purpose of this study is to illustrate the appearance of contrast flow in the retrodural retroligamentous space of Okada during computed tomography– and fluoroscopy-guided cervical and lumbar transforaminal epidural steroid injections.

Design

This retrospective study will use a series of cases to demonstrate contrast within the space of Okada during epidural transforaminal steroid injections.

Setting

Tertiary medical center.

Subjects

Study subjects are adult patients who underwent transforaminal epidural steroid injection at our institution.

Methods

Cases were identified through the use of a search engine of existing radiology reports at our institution. Epidural steroid injection procedural reports were searched for the terms “Okada” and “retrodural space.” Images from the procedure were reviewed by the authors (all proceduralists with dedicated training in spinal injections) to confirm the presence of contrast within the space of Okada.

Results

This case series illustrates six examples of contrast injection into the retrodural space of Okada during cervical and lumbar transforaminal epidural steroid injections.

Conclusions

Contrast uptake in the retrodural space of Okada may be seen during transforaminal epidural injections. Although relatively uncommon, it is likely underrecognized. It is extremely important that providers who perform transforaminal epidural steroid injections be familiar with this non-epidural contrast flow pattern so they can adjust needle positioning to deliver steroid to the epidural space.
Predictors of progression to systemic sclerosis: analysis of very early diagnosis of systemic sclerosis in a large single-centre cohort
Authors: Siqueira Valdirene S , Helbingen Mariely F S , Medeiros-Ribeiro Ana Cristina , Carriço da Silva Henrique , Miossi Renata , Luppino-Assad Ana Paula , Sampaio-Barros Percival D
Published: January 2022

Objective

This study analysed the very early disease of SSc (VEDOSS) characteristics in a group of 217 patients with RP and at least one manifestation of SSc in search of predictors for the progression to SSc.

Methods

This was a cross-sectional single-centre analysis of patients presenting with RP with a specific SSc clinical manifestation or SSc autoantibody or SD pattern at nailfold capillaroscopy (SD-NFC), without skin involvement, who attended a scleroderma outpatient clinic between 2010 and 2019. The performance of VEDOSS and the importance of the combination of VEDOSS characteristics to predict the progression to SSc were evaluated.

Results

Among 217 patients, 153 (70.5%) were classified as SSc, including 65 (30%) in the first investigation; 69.3% of the SSc patients met VEDOSS criteria compared with 6.3% of patients who did not progress to SSc. The combinations most associated with progression to SSc were RP + puffy fingers (PF) + positive ANA + SD-NFC and/or SSc-specific antibody (VEDOSS level 2), with an odds ratio (OR) of 19.52 (95% CI 4.48, 85.06; P < 0.001) and RP + PF + positive ANA (VEDOSS level 1; ‘red flags’) (OR 15.45; P < 0.001), while combinations without non-RP clinical symptoms, as RP + SD-NFC (OR 0.03; P < 0.001) and RP + anticentromere + SD-NFC (OR 0.06; P = 0.006) were associated with non-progression to SSc.

Conclusion

Among patients with RP with at least one manifestation of SSc, without skin involvement, combinations of VEDOSS characteristics were the strongest predictors of progression to SSc at a median follow-up of 4 years.
A METHOD TO IDENTIFY AND LOCALIZE A SINGLE HOT PARTICLE IN THE LUNGS USING AN ARRAY OF HIGH-PURITY GERMANIUM DETECTORS FOR IMPROVED ESTIMATE OF THE DEPOSITED ACTIVITY
Authors: Aviv O , Epstein L , Fried Y , Spitz H B , Shonkor S , Epstein D , Naim A , Yungrais Z , Datz H
Published: January 2022

A new method has been developed to identify and localize a single hot particle in the lungs using an array of four high-purity germanium detectors. The method is based upon calculating a set of three count rate ratios (generated by each individual detector in the array) that are evaluated in sequence to designate whether the measured deposition can be associated with a hot particle rather than the default assumption of a uniform activity distribution. Identification and localization of the hot particle are determined from a single in vivo measurement in which detectors are positioned above and below the thorax. The method was tested using an anthropomorphic thorax phantom in which point sources of 241Am, 137Cs and 60Co were individually inserted in the lungs at 15 different locations and were measured using a scanning bed whole-body counter. Depending upon source location and photon energy, a bias of −35% up to +76% could be introduced by falsely assuming a uniform activity distribution in the lungs. This bias would directly translate to an erroneous dose estimate to the lungs. It was demonstrated that by using the appropriate detector efficiencies for the single hot particle, the bias associated with the activity determination is reduced to <10% and ~2% in average.
Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer
Authors: Colombo Nicoletta , Dubot Coraline , Lorusso Domenica , Caceres M. Valeria , Hasegawa Kosei , Shapira-Frommer Ronnie , Tewari Krishnansu S. , Salman Pamela , Usta Edwin Hoyos , Yañez Eduardo , Gümüş Mahmut , Olivera Hurtado de Mendoza Mivael , Samouëlian Vanessa , Castonguay Vincent , Arkhipov Alexander , Toker Sarper , Li Kan , Keefe Stephen M. , Monk Bradley J.
Published: January 2022

(Abstracted from N Engl J Med 2021;385:1856–1867)

Platinum-based chemotherapy plus bevacizumab and paclitaxel is the standard first-line therapy for persistent, recurrent, or metastatic cervical cancer. The phase 2 KEYNOTE-158 trial found evidence of a response to pembrolizumab among patients with programmed death ligand-1 (PD-L1) positive cervical cancer.
Effect of an Active vs Expectant Management Strategy on Successful Resolution of Pregnancy Among Patients With a Persisting Pregnancy of Unknown Location: The ACT or NOT Randomized Clinical Trial
Authors: Barnhart Kurt T. , Hansen Karl R. , Stephenson Mary D. , Usadi Rebecca , Steiner Anne Z. , Cedars Marcelle I. , Jungheim Emily S. , Hoeger Kathleen M. , Krawetz Stephen A. , Mills Benjie , Alston Meredith , Coutifaris Christos , Senapati Suneeta , Sonalkar Sarita , Diamond Michael P. , Wild Robert A. , Rosen Mitchell , Sammel Mary D. , Santoro Nanette , Eisenberg Esther , Huang Hao , Zhang Heping
Published: January 2022

(Abstracted from JAMA 2021;326:390–400)

Ultrasound cannot always diagnose early pregnancy failure. An intrauterine or extrauterine pregnancy and its location are not identifiable in up to 40% of pregnant women presenting for evaluation.
Stepwise Approach to the Management of Endometriosis-Related Dysmenorrhea: A Cost-Effectiveness Analysis
Authors: Bohn Jacqueline A. , Bullard Kimberley A. , Rodriguez Maria I. , Ecker Amanda M.
Published: January 2022

(Abstracted from Obstet Gynecol 2021;138:557–564)

Endometriosis is a highly morbid condition, globally affecting millions of women. Up to 10% of reproductive-aged women are affected.
A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection
Authors: Hughes Brenna L. , Clifton Rebecca G. , Rouse Dwight J. , Saade George R. , Dinsmoor Mara J. , Reddy Uma M. , Pass Robert , Allard Donna , Mallett Gail , Fette Lida M. , Gyamfi-Bannerman Cynthia , Varner Michael W. , Goodnight William H. , Tita Alan T. N. , Costantine Maged M. , Swamy Geeta K. , Gibbs Ronald S. , Chien Edward K. , Chauhan Suneet P. , El-Sayed Yasser Y. , Casey Brian M. , Parry Samuel , Simhan Hyagriv N. , Napolitano Peter G. , Macones George A.
Published: January 2022

(Abstracted from N Engl J Med 2021;385:436–444)

Congenital cytomegalovirus (CMV) infections are associated with stillbirth, neonatal death, deafness, and cognitive and motor delay. Small observational studies have evaluated CMV hyperimmune globulin to prevent congenital infection in women with primary CMV infection during pregnancy; however, the results were either inconsistent or inconclusive.
The Arabin Pessary to Prevent Preterm Birth in Women With a Twin Pregnancy and a Short Cervix: The STOPPIT 2 RCT
Authors: Norman Jane E. , Norrie John , MacLennan Graeme , Cooper David , Whyte Sonia , Chowdhry Sushila , Cunningham-Burley Sarah , Neilson Aileen R. , Mei Xue W. , Smith Joel B. E. , Shennan Andrew , Robson Stephen C. , Thornton Steven , Kilby Mark D. , Marlow Neil , Stock Sarah J. , Bennett Philip R. , Denton Jane ,   on behalf of the STOPPIT Collaborative Group
Published: January 2022

(Abstracted from Health Technol Assess 2021;25:1–66)

In England and Wales, approximately 16 of every 1000 women have a multiple gestation. Multiple pregnancies are associated with higher rates of stillbirth and neonatal and infant mortality, as well as child disability compared with singleton pregnancies.
Blood Pressure Thresholds in Pregnancy for Identifying Maternal and Infant Risk: A Secondary Analysis of Community-Level Interventions for Pre-Eclampsia (CLIP) Trial Data
Authors: Bone Jeffrey N. , Magee Laura A. , Singer Joel , Nathan Hannah , Qureshi Rahat N. , Sacoor Charfudin , Sevene Esperança , Shennan Andrew , Bellad Mrutyunjaya B. , Goudar Shivaprasad S. , Mallapur Ashalata A. , Munguambe Khátia , Vidler Marianne , Bhutta Zulfiqar A. , von Dadelszen Peter
Published: January 2022

(Abstracted from Lancet Glob Health 2021;9:e1119–e1128)

Hypertension in pregnancy (HIP) has served as a marker for increased risk of adverse pregnancy outcomes, including fetal growth restriction, stillbirth, severe maternal morbidity, and maternal mortality. Traditionally, HIP has been defined as systolic blood pressure (sBP) of ≥140 mm Hg, diastolic BP (dBP) of ≥90 mm Hg, or both.
Out-of-Pocket Spending for Deliveries and Newborn Hospitalizations Among the Privately Insured
Authors: Chua Kao-Ping , Fendrick A. Mark , Conti Rena M. , Moniz Michelle H.
Published: January 2022

(Abstracted from Pediatrics 2021;148(1):e2021050552)

Previous studies on the financial burden of childbirth on privately insured families have been focused on the out-of-pocket costs of maternal care, including hospitalization for delivery. However, there are no recent data that has considered the out-of-pocket spending on hospital stays for delivery and neonatal intensive care.
Routine Postoperative Computed Tomography Scans Following Posterior Pelvic Fixation of Pelvic Ring Fractures: A Survey of (OTA) Orthopaedic Traumatologists
Authors: Thompson David M. , Ricci Alfred Gianni , Floyd John C. P. , Jardaly Achraf H. , Ziran Bruce H. , Harris Robert M.
Published: January 2022

Objective:

To assess practices related to ordering computed tomography (CT) scans routinely after posterior pelvic ring fixation and revision surgery rates.

Design:

A 20-question cross-sectional survey.

Participants:

Fellowship-trained orthopaedic traumatologists.

Main Outcome Measurements:

(1) Percentage of surgeons ordering a routing postoperative CT after posterior pelvic ring fixation, (2) Revision surgery rates based on routine CT scan results.

Results:

Responses were received from 57 surgeons. Practices varied regarding postoperative CT scans, with 20 surgeons (35%, group A) routinely ordering them and 37 surgeons (65%, group B) not ordering them on all patients. Group A were younger and with less years of experience than those in Group B. Most group A surgeons report a revision surgery rate of <1% based on results of the postoperative CT. Group A report routine postoperative scans were obtained to assess reduction, instrumentation placement, and for educational purposes. Group B did not obtain routine postoperative CTs because of the following: unlikely to change postoperative treatment course, adequate reduction and instrumentation placement assessed intraoperatively and by postoperative radiographs, and increased radiation exposure and cost to patients. Group B did report obtaining postop CT scans on select patients, with postoperative neurological deficit being the most common indication.

Conclusions:

The routine use of postoperative CTs following posterior fixation of pelvic ring fractures is a controversial topic. Although we recognize the role for postoperative CT scans in select patients, our study questions the clinical utility of these scans in all patients and in conclusion do not recommend this protocol.
Saline Compared to Balanced Crystalloid in Patients With Diabetic Ketoacidosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Alghamdi Naif Ali , Major Paityn , Chaudhuri Dipayan , Tsui Janice , Brown Brent , Self Wesley H. , Semler Matthew W. , Ramanan Mahesh , Rochwerg Bram
Published: January 2022

OBJECTIVES:

This systematic review and meta-analysis compared the use of saline to balanced crystalloid for fluid resuscitation in patients with diabetic ketoacidosis (DKA).

DATA SOURCES:

We searched databases including Medline, Embase, and the Cochrane registry.

STUDY SELECTION:

We included randomized controlled trials (RCTs) that compared saline to balanced crystalloid in patients with DKA.

DATA EXTRACTION:

We pooled estimates of effect using relative risk for dichotomous outcomes and mean differences (MDs) for continuous outcomes, both with 95% CIs. We assessed risk of bias for included RCTs using the modified Cochrane tool and certainty of evidence using Grading of Recommendations, Assessment, Development, and Evaluation methodology.

DATA SYNTHESIS:

We included eight RCTs (n = 482 patients). Both time to DKA resolution (MD, 3.51 hr longer; 95% CI, 0.90 longer to 6.12 longer; moderate certainty) and length of hospital stay (MD, 0.89 d longer in saline group; 95% CI, 0.34 longer to 1.43 d longer; moderate certainty) are probably longer in the saline group compared with the balanced crystalloid group, although for the latter, the absolute difference (under 1 d) is small. Post-resuscitation serum chloride level may be higher (MD, 1.62 mmol/L higher; 95% CI, 0.40 lower to 3.64 higher; low certainty), and post-resuscitation serum bicarbonate is probably lower (MD, 1.50 mmol/L; 95% CI, 2.33 lower to 0.67 lower; moderate certainty) in those receiving saline.

CONCLUSIONS:

In patients with DKA, the use of saline may be associated with longer time to DKA resolution, higher post-resuscitation serum chloride levels, lower post-resuscitation serum bicarbonate levels, and longer hospital stay compared with balanced crystalloids. Pending further data, low to moderate certainty data support using balanced crystalloid over saline for fluid resuscitation in patients with DKA.
Brain Biopsy for Neurological Diseases of Unknown Etiology in Critically Ill Patients: Feasibility, Safety, and Diagnostic Yield
Authors: Mathon Bertrand , Favreau Malory , Degos Vincent , Amelot Aymeric , Le Joncour Alexandre , Weiss Nicolas , Rohaut Benjamin , Le Guennec Loïc , Boch Anne-Laure , Carpentier Alexandre , Bielle Franck , Mokhtari Karima , Idbaih Ahmed , Touat Mehdi , Combes Alain , Demoule Alexandre , Shotar Eimad , Navarro Vincent , Raux Mathieu , Demeret Sophie , Pineton De Chambrun Marc ,   on behalf of the PSL BRAIN-BIOPSY STUDY GROUP
Published: January 2022

OBJECTIVES:

Brain biopsy is a useful surgical procedure in the management of patients with suspected neoplastic lesions. Its role in neurologic diseases of unknown etiology remains controversial, especially in ICU patients. This study was undertaken to determine the feasibility, safety, and the diagnostic yield of brain biopsy in critically ill patients with neurologic diseases of unknown etiology. We also aimed to compare these endpoints to those of non-ICU patients who underwent a brain biopsy in the same clinical context.

DESIGN:

Monocenter, retrospective, observational cohort study.

SETTING:

A French tertiary center.

PATIENTS:

All adult patients with neurologic diseases of unknown etiology under mechanical ventilation undergoing in-ICU brain biopsy between January 2008 and October 2020 were compared with a cohort of non-ICU patients.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Among the 2,207 brain-biopsied patients during the study period, 234 biopsies were performed for neurologic diseases of unknown etiology, including 29 who were mechanically ventilated and 205 who were not ICU patients. Specific histological diagnosis and final diagnosis rates were 62.1% and 75.9%, respectively, leading to therapeutic management modification in 62.1% of cases. Meningitis on prebiopsy cerebrospinal fluid analysis was the sole predictor of obtaining a final diagnosis (2.3 [1.4–3.8]; p = 0.02). ICU patients who experienced therapeutic management modification after the biopsy had longer survival (p = 0.03). The grade 1 to 4 (mild to severe) complication rates were: 24.1%, 3.5%, 0%, and 6.9%, respectively. Biopsy-related mortality was significantly higher in ICU patients compared with non-ICU patients (6.9% vs 0%; p = 0.02). Hematological malignancy was associated with biopsy-related mortality (1.5 [1.01–2.6]; p = 0.04).

CONCLUSIONS:

Brain biopsy in critically ill patients with neurologic disease of unknown etiology is associated with high diagnostic yield, therapeutic modifications and postbiopsy survival advantage. Safety profile seems acceptable in most patients. The benefit/risk ratio of brain biopsy in this population should be carefully weighted.