bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract

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

Abstract

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 &lt; 0.001) and RP + PF + positive ANA (VEDOSS level 1; ‘red flags’) (OR 15.45; P &lt; 0.001), while combinations without non-RP clinical symptoms, as RP + SD-NFC (OR 0.03; P &lt; 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

Abstract
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 &lt;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.