bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smurf2 inhibition enhances chemotherapy and radiation sensitivity in non-small-cell lung cancer
Authors: Chaudhary Kunal R. , Kinslow Connor J. , Cheng Haiying , Silva Jose M. , Yu Jiyang , Wang Tony. J. , Hei Tom K. , Halmos Balazs , Cheng Simon K. 
Published: June 2022

AbstractLung cancer has been the most common cancer worldwide for several decades. The outcomes of patients with locally advanced lung cancer remain dismal, and only a minority of patients survive more than 5 years. However, tumor therapeutic resistance mechanisms are poorly studied. Identification of therapeutic resistance pathways in lung cancer in order to increase the sensitivity of lung tumor cells to therapeutic agents is a crucial but challenging need. To identify novel genes that modulate the response to platinum-based therapy, we performed a genome-wide high-throughput ribonucleic acid interference (RNAi) screen via transfection of human lung cancer (PC9) cells with a viral short hairpin RNA (shRNA) library. We further validated a potential target via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenic survival assays on PC9 and A549 lung tumor cells transfected with small interfering RNAs (siRNAs) to successfully downregulate protein expression and then treated with increasing doses of cisplatin or X-ray radiation. We determined protein expression by immunohistochemistry (IHC) after chemoradiotherapy and analyzed gene expression-based survival outcomes in two cohorts of human non-small-cell lung cancer (NSCLC) patients. The screen identified several targets involved in epithelial-to-mesenchymal transition (EMT), including Smurf1, Smurf2, YAP1, and CEBPZ, and glycolytic pathway proteins, including PFKFB3. Furthermore, we found that the small molecule proteasome inhibitor bortezomib significantly downregulated Smurf2 in lung cancer cells. The addition of bortezomib in combination with cisplatin and radiation therapy in PC9 and A549 cells led to an increase in deoxyribonucleic acid (DNA) double-strand breaks with increased numbers of γ-H2AX-positive cells and upregulation of apoptosis. Finally, we found that Smurf2 protein expression was upregulated in situ after treatment with cisplatin and radiation therapy in a relevant cohort of patients with stage III NSCLC. Additionally, Smurf2 gene expression was the strongest predictor of survival in patients with squamous NSCLC after chemotherapy or chemoradiotherapy. We successfully identified and validated Smurf2 as both a common modulator of resistance and an actionable target in lung cancer. These results suggest the urgent need to investigate clinical Smurf2 inhibition via bortezomib in combination with cisplatin and radiation for patients with locally advanced NSCLC.
The influence of laser-induced alignment on Z-scan properties of 2D carbon nanomaterials suspension dependent on polarization
Authors: Zhang Qiuhui , Wu Xinghui , Han Jinghua 
Published: June 2022

AbstractThe Z-scan technique uses a single beam that can be used for observing the nonlinear or optical limiting properties of materials. For the first time, the Z-scan properties dependent on the polarization of 2D carbon nanomaterial suspension were experimentally investigated using optical Z-scan technology. The Z-scan curves of graphene and graphene oxide (GO) in N-methyl-2-pyrrolidinone suspensions exhibited strong polarization-dependent characteristics. In paper, a reverse saturated absorption (RSA) dip surrounded the lens focus when the horizontal polarized beam was focused in the suspension, and two saturated absorption (SA) peaks appeared adjacent to the dip. However, for the vertical polarized beam, only one RSA dip surrounded the lens focus, and the threshold was higher than the SA for a horizontally polarized beam. The transmission of RSA for the GO suspension was evidently lower than that of the graphene suspension. The polarization-dependent characteristic can be ascribed to the laser-induced alignment in case the suspension is moved in or out of the beam focal point. Furthermore, the polarization-dependent 2D carbon nanomaterial suspension can be applied in several practical purposes such as 2D material-based optical and opto-fludic devices.
Genome-wide meta-analysis of iron status biomarkers and the effect of iron on all-cause mortality in HUNT
Authors: Moksnes Marta R. , Graham Sarah E. , Wu Kuan-Han , Hansen Ailin Falkmo , Gagliano Taliun Sarah A. , Zhou Wei , Thorstensen Ketil , Fritsche Lars G. , Gill Dipender , Mason Amy , Cucca Francesco , Schlessinger David , Abecasis Gonçalo R. , Burgess Stephen , Åsvold Bjørn Olav , Nielsen Jonas B. , Hveem Kristian , Willer Cristen J. , Brumpton Ben M. 
Published: June 2022

AbstractIron is essential for many biological processes, but iron levels must be tightly regulated to avoid harmful effects of both iron deficiency and overload. Here, we perform genome-wide association studies on four iron-related biomarkers (serum iron, serum ferritin, transferrin saturation, total iron-binding capacity) in the Trøndelag Health Study (HUNT), the Michigan Genomics Initiative (MGI), and the SardiNIA study, followed by their meta-analysis with publicly available summary statistics, analyzing up to 257,953 individuals. We identify 123 genetic loci associated with iron traits. Among 19 novel protein-altering variants, we observe a rare missense variant (rs367731784) in HUNT, which suggests a role forDNAJC13in transferrin recycling. We further validate recently published results using genetic risk scores for each biomarker in HUNT (6% variance in serum iron explained) and present linear and non-linear Mendelian randomization analyses of the traits on all-cause mortality. We find evidence of a harmful effect of increased serum iron and transferrin saturation in linear analyses that estimate population-averaged effects. However, there was weak evidence of a protective effect of increasing serum iron at the very low end of its distribution. Our findings contribute to our understanding of the genes affecting iron status and its consequences on human health.
Biotic induction and microbial ecological dynamics of Oceanic Anoxic Event 2
Authors: Connock Gregory T. , Owens Jeremy D. , Liu Xiao-Lei 
Published: June 2022

AbstractUnderstanding the causal mechanisms of past marine deoxygenation is critical to predicting the long-term Earth systems response to climate change. However, the processes and events preceding widespread carbon burial coincident with oceanic anoxic events remain poorly constrained. Here, we report a comprehensive biomarker inventory enveloping Oceanic Anoxic Event 2 that captures microbial communities spanning epipelagic to benthic environments in the southern proto-North Atlantic Ocean. We identify an abrupt, sustained increase in primary productivity that predates Oceanic Anoxic Event 2 by ∼220 ± 4 thousand years, well before other geochemical proxies register biogeochemical perturbations. During the event, recurrent photic zone euxinia triggered a major marine microbial reorganization accompanied by a decrease in primary production. These findings highlight how organic carbon burial drivers operated along a continuum in concert with microbial ecological changes, with antecedent, localized increases in primary production destabilizing carbon cycling and promoting the progressive marine deoxygenation leading to Oceanic Anoxic Event 2.
Molecular mechanisms of cystic fibrosis – how mutations lead to misfunction and guide therapy
Authors: Farinha Carlos M. , Callebaut Isabelle 
Published: June 2022

Abstract
Cystic fibrosis, the most common autosomal recessive disorder in Caucasians, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a cAMP-activated chloride and bicarbonate channel that regulates ion and water transport in secretory epithelia. Although all mutations lead to the lack or reduction in channel function, the mechanisms through which this occurs are diverse – ranging from lack of full-length mRNA, reduced mRNA levels, impaired folding and trafficking, targeting to degradation, decreased gating or conductance, and reduced protein levels to decreased half-life at the plasma membrane. Here, we review the different molecular mechanisms that cause cystic fibrosis and detail how these differences identify theratypes that can inform the use of directed therapies aiming at correcting the basic defect. In summary, we travel through CFTR life cycle from the gene to function, identifying what can go wrong and what can be targeted in terms of the different types of therapeutic approaches.
Perceptions and Attitudes toward COVID-19 Vaccination among Pregnant and Postpartum Individuals
Authors: Siegel Molly R. , Lumbreras-Marquez Mario I. , James Kaitlyn , McBay Brandon R. , Gray Kathryn J. , Schantz-Dunn Julianna , Diouf Khady , Goldfarb Ilona T. 
Published: June 2022

Objective This study aimed to characterize attitudes toward novel coronavirus disease 2019 (COVID-19) vaccination and to evaluate factors associated with vaccine uptake among pregnant individuals.
Study Design An anonymous survey was distributed to a convenience sample of pregnant individuals receiving prenatal care at two large urban academic hospitals in a single health care network in Massachusetts. Individual demographic variables were included in the survey along with questions assessing attitudes toward COVID-19 and vaccination in pregnancy. Data were analyzed using parametric or nonparametric tests when appropriate, and associated odds ratios (OR) were calculated via univariable logistic regression.
Results There were 684 surveys distributed, and 477 pregnant and postpartum individuals completed the survey, for a response rate of 69.7%. Overall, 233 (49.3%) had received or were scheduled to receive a COVID-19 vaccine. Age, White race, non-Hispanic or Latinx ethnicity, working from home, and typical receipt of the influenza vaccine were associated with COVID-19 vaccination. Further, 276 respondents (58.4%) reported that their provider recommended the COVID-19 vaccine in pregnancy; these participants were more likely to have received a vaccine (OR = 5.82, 95% confidence interval [CI]: 3.68–9.26, p < 0.005). Vaccinated individuals were less likely to be worried about the effects of the vaccine on themselves (OR = 0.18, 95% CI: 0.12–0.27, p < 0.005) or their developing babies (OR = 0.17, 95% CI: 0.11–0.26, p < 0.005). Unvaccinated individuals were less likely to report that it is easy to schedule a COVID-19 vaccine (OR = 0.56, 95% CI: 0.34–0.93, p = 0.02), to travel to receive a vaccine (OR = 0.19, 95% CI: 0.10–0.36, p < 0.005), and to miss work to receive a vaccine (OR = 0.30, 95% CI: 0.18–0.48, p < 0.005).
Conclusion Strategies are needed to improve patient education regarding vaccine side effects and safety in pregnancy. Policy changes should focus on making it feasible for patients to schedule a vaccine and miss work without loss of pay to get vaccinated.
Key Points
Impact of the COVID-19 Pandemic on Prenatal Care Utilization at a Public Hospital
Authors: Boguslawski Shae M. , Joseph Naima T. , Stanhope Kaitlyn K. , Ti Angeline J. , Geary Franklyn H. , Boulet Sheree L. 
Published: June 2022

Objective The aim of the study is to compare rates of prenatal care utilization before and after implementation of a telehealth-supplemented prenatal care model due to the coronavirus disease 2019 (COVID-19) pandemic.
Study Design Using electronic medical record data, we identified two cohorts of pregnant persons that initiated prenatal care prior to and during the COVID-19 pandemic following the implementation of telehealth (from March 1, 2019 through August 31, 2019, and from March 1, 2020, through August 31, 2020, respectively) at Grady Memorial Hospital. We used Pearson's Chi-square and two-tailed t-tests to compare rates of prenatal care utilization, antenatal screening and immunizations, emergency department and obstetric triage visits, and pregnancy complications for the prepandemic versus pandemic-exposed cohorts.
Results We identified 1,758 pregnant patients; 965 entered prenatal care prior to the COVID-19 pandemic and 793 entered during the pandemic. Patients in the pandemic-exposed cohort were more likely to initiate prenatal care in the first trimester (46.1 vs. 39.0%, p = 0.01), be screened for gestational diabetes (74.4 vs. 67.0%, p <0.001), and receive dating and anatomy ultrasounds (17.8 vs. 13.0%, p = 0.006 and 56.9 vs. 47.3%, p <0.001, respectively) compared with patients in the prepandemic cohort. There was no difference in mean number of prenatal care visits between the two groups (6.9 vs. 7.1, p = 0.18). Approximately 41% of patients in the pandemic-exposed cohort had one or more telehealth visits. The proportion of patients with one or more emergency department visits was higher in the pandemic-exposed cohort than the prepandemic cohort (32.8 vs. 12.3%, p < 0.001). Increases in rates of labor induction were also observed among the pandemic-exposed cohort (47.1 vs. 38.2%, p <0.001).
Conclusion Rates of prenatal care utilization were similar before and during the COVID-19 pandemic. However, pregnant persons receiving prenatal care during the pandemic entered care earlier and had higher utilization of certain antenatal screening services than those receiving prenatal care prior to the pandemic.
Key Points
Survival and Neurodevelopmental Outcomes in Congenital Diaphragmatic Hernia Patients with Single versus Repeat Extracorporeal Membrane Oxygenation Runs
Authors: Herco Maja , Sloan Patrick , Vogel Adam , Vrecenak Jesse , Najaf Tasnim 
Published: June 2022

Objective We describe the survival and neurodevelopmental outcomes of congenital diaphragmatic hernia (CDH) patients who received single and repeat extracorporeal membrane oxygenation (ECMO).
Study Design This is a retrospective single-center study comparing neurodevelopmental outcomes in CDH patients who were managed without ECMO, who received one ECMO run, and those who received two ECMO runs. Neurodevelopmental testing was performed utilizing the Bayley Scales of Infant Development-III.
Results There were 68 neonates identified with CDH from January 2011 to June 2019: 30 did not receive ECMO, 29 received single ECMO run, and 9 received two ECMO runs. Survival of ECMO patients was 50%, with 48% of single run and 57% of repeat run patients surviving to discharge. Second-run ECMO patients had increased median ventilator days (60 vs. 33, p = 0.04) and increased median length of hospital stay (159 vs. 89, p = 0.01). Neurodevelopmental testing via Bayley Scales of Infant Development-III was performed on 74% of survivors at the mean age of 24 months. CDH neonates who underwent ECMO (single or repeat runs) were more likely to have lower cognitive, language, and motor composite scores as compared with CDH neonates who had not required ECMO. Motor composite scores were significantly lower in repeat ECMO run neonates as compared with single ECMO run (72 + 6 vs. 85 + 4, p = 0.0003), but there were no further deficits noted in language or cognitive domains.
Conclusion Survival after a second ECMO run in CDH is possible, although with increased ventilator days and increased length of hospitalization. We also find further deficits in motor outcomes in the second-run ECMO group compared with single-run ECMO. Our findings do not preclude a second ECMO run, but rather inform our counseling to families and reinforce the need for close neurodevelopmental follow-up for these patients.
Key Points
Confirmatory Middle Cerebral Artery Doppler Testing in Alloimmunized Patients with Suspected Fetal Anemia
Authors: Richards Douglas S. , Benson Ashley E. , Einerson Brett D. 
Published: June 2022

Objective This article aimed to evaluate pregnancy outcomes when a plan to perform fetal blood sampling (FBS) or delivery was based solely on the first abnormal middle cerebral artery peak velocity (MCA-PV) measurement compared with making a plan after a confirmatory test on a subsequent day.
Study Design We performed a descriptive study of pregnancy outcomes including all patients in a single healthcare system with maternal red cell alloimmunization undergoing ultrasound between 2005 and 2017 who had at least one MCA-PV>1.5 multiples of the median (MoM). We excluded patients with any sign of hydrops prior to the index visit or abnormal MCA-PV at>35 weeks. The first exam with a MCA-PV>1.5 MoM was deemed the index visit.
Results Fifty patients were identified. Twenty-one patients underwent intervention (FBS or delivery) based on the first abnormal MCA-PV. Of those, 9 had moderate or severe anemia (positive predictive value [PPV]: 43%), while 12 had mild or no anemia. The other 29 patients underwent a confirmatory MCA test between 2 and 8 days later. Of these, 13 patients had an abnormal confirmatory test and 11 of these underwent FBS and 7 had moderate or severe anemia (PPV: 54%). Sixteen patients undergoing confirmatory MCA Doppler had a normal test on repeat and did not undergo FBS. Of those, none developed moderate or severe anemia.
Conclusion A substantial number of patients (55%) had normal MCA-PV testing on repeat, allowing avoidance of invasive testing. Deferring FBS until the abnormal MCA-PV was confirmed was not associated with undetected moderate or severe anemia.
Key Points
Survey of Obstetric Providers to Assess the Knowledge and Management of a Reported Penicillin Allergy in Pregnant Women
Authors: Cate Jennifer J. M. , Burn Martina , Kwah Jason , Liao Jane , Illuzzi Jessica , Reddy Uma , Son Moeun 
Published: June 2022

Objective Penicillin allergy is the most commonly reported drug allergy in the United States; however, less than 10% of individuals labeled with a penicillin allergy are truly allergic. A reported penicillin allergy in pregnancy is associated with adverse maternal and perinatal outcomes. Despite recommendations for penicillin allergy testing in pregnancy, limited literature regarding obstetric providers' comfort and knowledge in addressing penicillin allergy and referral patterns exists. The objective of this study is to survey obstetric providers to assess their clinical practice patterns and baseline penicillin allergy knowledge, identify potential knowledge gaps in the management of pregnant patients with reported penicillin allergy, and measure the impact of an educational intervention on provider knowledge and practice patterns.
Study Design An anonymous, electronic 23-question survey administered to all obstetric providers at a single academic medical center assessed obstetric provider characteristics, self-reported antibiotic practice patterns, and antibiotic allergy knowledge before (June 19, 2020) and after (September 16, 2020) a penicillin allergy educational intervention, which consisted of multiple small-group educational sessions and a culminating departmental educational session. Discrete knowledge comparison by provider type and experience level of pre- and postintervention was performed using chi-square tests.
Results Of 277 obstetric providers invited, 124 (45%) responded preintervention and 62 (22%) postintervention. In total, 27% correctly identified the percentage of patients labeled penicillin allergic who would tolerate penicillins, 45% identified cephalosporin cross-reactivity, 59% understood penicillin allergies can wane, and 54% identified penicillin skin testing (PST) as a valid allergy verification tool. Among 48 respondents who attended educational sessions and responded postintervention, their knowledge of penicillin allergy waning (79% preeducation vs. 98% posteducation, p < 0.01) and PST as a valid tool for penicillin allergy verification (50% preeducation vs. 83% posteducation, p < 0.01) improved.
Conclusion Knowledge gaps related to penicillin allergy exist among obstetric providers. Educational initiatives may improve provider knowledge, help in the identification of patients requiring penicillin allergy evaluation, and reduce referral barriers.
Key Points
Segregation-induced Ge precipitation in Ge2Sb2Te5 and N-doped Ge2Sb2Te5 line cells
Authors: Xu Qiyun , Lian Enkui , Yeoh Phoebe , Skowronski Marek 
Published: June 2022

Electromigration in Ge2Sb2Te5 and N-doped Ge2Sb2Te5 line cell structures has been studied by mapping out electric field/current-induced composition changes using x-ray energy dispersive spectroscopy. Both materials exhibit pronounced segregation in a molten state, with Te moving toward the anode and Ge and Sb toward the cathode. The width of the transition region from a composition of over 90% Te to over 90% Ge–Sb was 500 nm for an electric field of 1.1 × 107 V/m. In the Ge–Sb-rich end of the cell, Ge precipitates out of the melt, forming almost pure Ge inclusions with a size up to 100 nm. The Ge–Sb–Te segregation and precipitation do not appear to be affected by doping with nitrogen.
Do we DARE? Improving digital ano-rectal examination in men who have sex with men living with HIV: a quality improvement initiative
Authors: Woodward Shannon C. , Tyson Alexandra H. , Martin Sarah J. 
Published: June 2022

Men who have sex with men (MSM) living with HIV are at increased risk of anal cancer and annual screening via digital ano-rectal examination (DARE) is recommended. Baseline audit (Cycle 1) was undertaken of the medical records of MSM living with HIV aged ≥50 years (n = 85) from 1 January 2017 to 31 December 2018, in line with guidelines at the time. Data collection included whether DARE was discussed and offered, and whether DARE was accepted or declined. We provided staff training and altered clinic proformas aiming to increase DARE. Audit Cycle 2 (Cycle 2) was undertaken of eligible MSM (n = 86) who attended between 1 January 2019 to 31 December 2020. DARE frequency increased from 4.7% in Cycle 1 to 41.8% in Cycle 2 (P < 0.001) and discussion and offer of DARE increased from 8% to 64% in Cycle 2 (P < 0.001).
Literature text as world reversing
Authors: Li Fang , Kellogg David 
Published: June 2022

Abstract
Because translators begin where authors end – with a completed text – their task may be conceptualized as a reverse worlding, or ascent from actual text to imaginary context. This article argues that the same is true, mutatis mutandis, for all verbal art, and that within verbal art, it is truer of the texts that Hasan (1985, 101) refers to as ‘literature text’ and less so of those she calls ‘literary text’ that have some extra-artistic purpose. We demonstrate this empirically using an extreme example, the lipogrammatic French novel La disparition (Perec 1969) and its English translation A Void (Perec 2008). We also argue for a certain chastity in theory – a theory of translation for verbal art which excludes both the nonverbal and texts that are not purposefully artistic. Moreover, we say that there needs to be a corresponding chastity in practice – a theory of world inversion that rests not on a political program, but rather on a scientific understanding of the world and the proper place of words within it.