bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cystic Fibrosis Increases Long-Term Revision Rates of Endoscopic Sinus Surgery in Patients With Comorbid Chronic Rhinosinusitis
Authors: Smith Kristine A. , Gill Amarbir S. , Beswick Daniel M. , Meeks Huong , Oakley Gretchen M. , Yim Michael , Curtin Karen , Orlandi Richard R. , Alt Jeremiah A. 
Published: October 2021

Background: Comorbid chronic rhinosinusitis (CRS) of adulthood is increasing among patients with cystic fibrosis (CF) due to improved median survival. However, little is known about the natural history of endoscopic sinus surgery (ESS) in this cohort. The objective of this study was to evaluate the revision rate of ESS and associated risk factors among adults with CRS and CF (CRSwCF). Methods: The Utah Population Database was queried for patients age >18 with CRS who underwent at least one ESS between 1996 and 2018. Demographic information and ESS history were collected and compared for CRSwCF versus CRS without CF (CRSsCF) using chi-square and t-tests. Risk factors for revision were analyzed using Cox proportional hazard models and logistic regression analysis. Results: A total of 34 050 patients (33 639 CRSsCF and 411 CRSwCF) were included in the final analysis. The mean duration of follow-up was 9.3 and 9.3 years, respectively ( P = .98). Adult patients with CF were significantly more likely to undergo revision ESS (18.7%) than those without CF (13.4%; P < .01). Logistic regression analysis indicated that a diagnosis of CF independently elevated the risk for revision ESS in the absence of nasal polyps (odds ratio [OR] 2.18, confidence interval [CI] 1.34-3.54), asthma (OR 1.36, CI 0.94-1.98), and allergies (OR 1.29, CI 0.90-1.73). Conclusion: In the era before highly effective modulator therapies, the mean revision rate of ESS among adults with CRSwCF was 18.7%, significantly greater than that of adults with CRSsCF. CF was an independent risk factor for revision ESS in the absence of nasal polyps, asthma, and allergies.
Development and Cultural Adaptation of a Computer-Delivered and Multi-Component Alcohol Reduction Intervention for Russian Women Living with HIV and HCV
Authors: Brown Jennifer L. , Anastasakis Iakovos , Revzina Natalia , Capasso Ariadna , Boeva Ekaterina , Rassokhin Vadim , Crusey Adrienne , Sales Jessica M. , Hitch Anthony , Renfro Tiffaney , DiClemente Ralph J. 
Published: October 2021

Background: There is elevated prevalence of problem drinking among Russian women living with HIV and HCV co-infection. This paper describes the development and cultural adaptation of a multi-component alcohol reduction intervention incorporating a brief, computer-delivered module for Russian women living with HIV and HCV co-infection. Methods: The format and content of the intervention were adapted to be linguistic-, cultural-, and gender-appropriate using the ADAPT-ITT framework. A computer-delivered module and brief clinician-delivered individual and telephone sessions were developed. Results: We describe the theoretical foundations of the intervention, the cultural adaptation of the intervention, and overview the content of the intervention’s multiple components. Discussion: Interventions to reduce alcohol use that can be integrated within Russian HIV treatment centers are urgently needed. If efficacious, the culturally-adapted intervention offers the promise of a cost-effective, easily disseminated intervention approach for Russian women living with HIV/HCV co-infection engaging in problematic alcohol use.
Comparing the Efficacy of Postoperative Pain Control Between Intravenous Parecoxib and Oral Diclofenac in ACL Reconstruction
Authors: Chuaychoosakoon Chaiwat , Parinyakhup Wachiraphan , Wiwatboworn Arnan , Purngpiputtrakul Peeranut , Wanasitchaiwat Pawin , Boonriong Tanarat 
Published: October 2021

Background: A nonsteroidal anti-inflammatory drug such as oral diclofenac is normally used to relieve postoperative pain after anterior cruciate ligament reconstruction (ACLR), but most patients continue to have moderate-to-severe pain that disturbs their rehabilitation. Some orthopaedists prefer to use intravenous (IV) parecoxib for postoperative pain control. Purpose: To compare the efficacy of IV parecoxib and oral diclofenac for postoperative pain control in ACLR. Study Design: Cohort study; Level of evidence, 3. Methods: We retrospectively collected and analyzed postoperative pain in patients who underwent both single- and double-bundle ACLR; pain was reported on a 10-point visual analog scale (VAS; 10 = worst pain). After the operation, each patient was given either IV parecoxib twice a day or oral diclofenac 3 times a day, and all patients received paracetamol 6 times per day for 24 hours postoperatively. If the patient complained of moderate or severe pain (VAS >3) after surgery, 3 mg of morphine would be given intravenously every 3 hours and 1 mg of morphine as a rescue analgesic every 1 hour for 24 hours postoperatively. Postoperative VAS and morphine consumption were recorded every 4 hours for 24 hours. Data were analyzed using paired t test, analysis of variance, and chi-square test. Results: Overall, 161 patients were included in this study, of whom 47 received IV parecoxib and 114 received oral diclofenac. The mean VAS scores at 4 and 8 hours postoperatively were 3.5 and 3.4, respectively, in the parecoxib group, and 4.4 and 4.7, respectively, in the diclofenac group. The parecoxib group had significantly lower mean VAS than the diclofenac group at 4 hours ( P = .047) and 8 hours ( P = .005), and the mean cumulative morphine consumption in the parecoxib group was significantly lower than in the diclofenac group at all time points ( P < .05) except 4 hours postoperatively. Conclusion: This study found that IV parecoxib was more effective than oral diclofenac in controlling postoperative pain and resulted in lower postoperative morphine consumption within the first 24 hours after ACLR.
Signatures of GVHD and relapse after posttransplant cyclophosphamide revealed by immune profiling and machine learning
Authors: McCurdy Shannon R. , Radojcic Vedran , Tsai Hua-Ling , Vulic Ante , Thompson Elizabeth , Ivcevic Sanja , Kanakry Christopher G. , Powell Jonathan D. , Lohman Brian , Adom Djamilatou , Paczesny Sophie , Cooke Kenneth R. , Jones Richard J. , Varadhan Ravi , Symons Heather J. , Luznik Leo 
Published: October 2021

Abstract
The key immunologic signatures associated with clinical outcomes after posttransplant cyclophosphamide (PTCy)-based HLA-haploidentical (haplo) and HLA-matched bone marrow transplantation (BMT) are largely unknown. To address this gap in knowledge, we used machine learning to decipher clinically relevant signatures from immunophenotypic, proteomic, and clinical data and then examined transcriptome changes in the lymphocyte subsets that predicted major posttransplant outcomes. Kinetics of immune subset reconstitution after day 28 were similar for 70 patients undergoing haplo and 75 patients undergoing HLA-matched BMT. Machine learning based on 35 candidate factors (10 clinical, 18 cellular, and 7 proteomic) revealed that combined elevations in effector CD4+ conventional T cells (Tconv) and CXCL9 at day 28 predicted acute graft-versus-host disease (aGVHD). Furthermore, higher NK cell counts predicted improved overall survival (OS) due to a reduction in both nonrelapse mortality and relapse. Transcriptional and flow-cytometric analyses of recovering lymphocytes in patients with aGVHD identified preserved hallmarks of functional CD4+ regulatory T cells (Tregs) while highlighting a Tconv-driven inflammatory and metabolic axis distinct from that seen with conventional GVHD prophylaxis. Patients developing early relapse displayed a loss of inflammatory gene signatures in NK cells and a transcriptional exhaustion phenotype in CD8+ T cells. Using a multimodality approach, we highlight the utility of systems biology in BMT biomarker discovery and offer a novel understanding of how PTCy influences alloimmune responses. Our work charts future directions for novel therapeutic interventions after these increasingly used GVHD prophylaxis platforms. Specimens collected on NCT0079656226 and NCT0080927627 https://clinicaltrials.gov/.
Iron status influences the response of cord blood megakaryocyte progenitors to eltrombopag in vitro
Authors: Liu Zhi-Jian , Deschmann Emoke , Ramsey Haley E. , Feldman Henry A. , Psaila Bethan , Cooper Nichola , Vlachodimitropoulou Evangelia , Porter John , Bussel James , Georgieff Michael , Sola-Visner Martha 
Published: October 2021

Abstract
Eltrombopag (ELT) is a thrombopoietic agent approved for immune thrombocytopenia and also a potent iron chelator. Here we found that ELT exhibited dose-dependent opposing effects on in vitro megakaryopoiesis: low concentrations (≤6 µM, ELT6) stimulated megakaryopoiesis, but high concentrations (30 µM, ELT30) suppressed megakaryocyte (MK) differentiation and proliferation. The suppressive effects of ELT30 were reproduced by other iron chelators, supporting iron chelation as a likely mechanism. During MK differentiation, committed MK progenitors (CD34+/CD41+ and CD34−/CD41+ cells) were significantly more sensitive than undifferentiated progenitors (CD34+/CD41− cells) to the suppressive effects of ELT30, which resulted from both decreased proliferation and increased apoptosis. The antiproliferative effects of ELT30 were reversed by increased iron in the culture, as were the proapoptotic effects when exposure to ELT30 was short. Because committed MK progenitors exhibited the highest proliferative rate and the highest sensitivity to iron chelation, we tested whether their iron status influenced their response to ELT during rapid cell expansion. In these studies, iron deficiency reduced the proliferation of CD41+ cells in response to all ELT concentrations. Severe iron deficiency also reduced the number of MKs generated in response to high thrombopoietin concentrations by ∼50%, compared with iron-replete cultures. Our findings support the hypothesis that although iron deficiency can stimulate certain cells and steps in megakaryopoiesis, it can also limit the proliferation of committed MK progenitors, with severity of iron deficiency and degree of thrombopoietic stimulation influencing the ultimate output. Further studies are needed to clarify how megakaryopoiesis, iron deficiency, and ELT stimulation are clinically interrelated.
A phase 2 multicenter trial of ofatumumab and prednisone as initial therapy for chronic graft-versus-host disease
Authors: Lazaryan Aleksandr , Lee Stephanie , Arora Mukta , Kim Jongphil , Betts Brian Christopher , Khimani Farhad , Nishihori Taiga , Bejanyan Nelli , Liu Hien , Kharfan-Dabaja Mohamed A. , Locke Frederick L. , Gonzalez Rebecca , Jain Michael D. , Davila Marco L. , Perez Lia Elena , Mishra Asmita , Perez Perez Ariel , Balke Karlie , Ayala Ernesto , Ochoa Leonel , Castaneda Puglianini Omar , Faramand Rawan , Alsina Melissa , Elmariah Hany , Nieder Michael L. , Fernandez Hugo , Anasetti Claudio , Pidala Joseph A. 
Published: October 2021

Abstract
Standard initial therapy of chronic graft vs. host disease (cGVHD) with glucocorticoids results in suboptimal response. Safety and feasibility of therapy with ofatumumab (1000 mg IV on days 0 and 14) and prednisone (1 mg/kg/day) was previously established in our phase I trial (n = 12). We now report the mature results of the phase II expansion of the trial (n = 38). The overall NIH severity of cGVHD was moderate (63%) or severe (37%) with 74% of all patients affected by the overlap subtype of cGVHD and 82% by prior acute cGVHD. The observed 6 month clinician-reported and 2014 NIH-defined overall response rates (ORR = complete + partial response [CR/PR]) of 62.5% (1-sided lower 90% confidence interval=51.5%) were not superior to pre-specified historic benchmark of 60%. Post-hoc comparison of 6 month NIH response suggested benefit compared to more contemporaneous NIH-based benchmark of 48.6% with frontline sirolimus/prednisone (CTN 0801 trial). Baseline cGVHD features (organ involvement, severity, initial immune suppression agents) were not significantly associated with 6-month ORR. The median time to initiation of second-line therapy was 5.4 months (range 0.9-15.1 months). Failure-free survival (FFS) was 64.2% (95% CI 46.5-77.4%) at 6 months and 53.1% (95% CI 35.8-67.7%) at 12 months, whereas FFS with CR/PR at 12 months of 33.5% exceeded a benchmark of 15% in post-hoc analysis, and was associated with greater success in steroid discontinuation by 24 months (odds ratio 8 (95% CI 1.21-52.7). This single-arm phase II trial demonstrated acceptable safety and potential efficacy of the upfront use of ofatumumab in combination with prednisone in cGVHD. This trial was registered at www.clinicaltrials.gov as #NCT01680965.
Surgical management of patients with von Willebrand disease: summary of 2 systematic reviews of the literature
Authors: Brignardello-Petersen Romina , El Alayli Abdallah , Husainat Nedaa , Kalot Mohamad , Shahid Shaneela , Aljabirii Yazan , Britt Alec , Alturkmani Hani , El-Khechen Hussein , Motaghi Shahrzad , Roller John , Dimassi Ahmad , Abughanimeh Omar , Madoukh Bader , Arapshian Alice , Grow Jean M. , Kouides Peter , Laffan Michael , Leebeek Frank W. G. , O’Brien Sarah H. , Tosetto Alberto , James Paula D. , Connell Nathan T. , Flood Veronica , Mustafa Reem A. 
Published: October 2021

Abstractvon Willebrand disease (VWD) is the most common inherited bleeding disorder. The management of patients with VWD who are undergoing surgeries is crucial to prevent bleeding complications. We systematically summarized the evidence on the management of patients with VWD who are undergoing major and minor surgeries to support the development of practice guidelines. We searched Medline and EMBASE from inception through October 2019 for randomized clinical trials (RCTs), comparative observational studies, and case series that compared maintaining factor VIII (FVIII) levels or von Willebrand factor (VWF) levels at &gt;0.50 IU/mL for at least 3 days in patients undergoing major surgery, and those with options for perioperative management of patients undergoing minor surgery. Two authors screened and abstracted data and assessed the risk of bias. We conducted meta-analyses when possible. We evaluated the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We included 7 case series for major surgeries and 2 RCTs and 12 case series for minor surgeries. Very-low-certainty evidence showed that maintaining FVIII levels or VWF levels of &gt;0.50 IU/mL for at least 3 consecutive days showed excellent hemostatic efficacy (as labeled by the researchers) after 74% to 100% of major surgeries. Low- to very-low-certainty evidence showed that prescribing tranexamic acid and increasing VWF levels to 0.50 IU/mL resulted in fewer bleeding complications after minor procedures compared with increasing VWF levels to 0.50 IU/mL alone. Given the low-quality evidence for guiding management decisions, a shared-decision model leading to individualized therapy plans will be important in patients with VWD who are undergoing surgical and invasive procedures.
Comparative studies on the mechanical properties and microstructures of outerwood and corewood in Pinus radiata D. Don
Authors: Li Ming-yue , Ren Hai-qing , Wang Yu-rong , Gong Ying-chun , Zhou Yong-dong 
Published: October 2021

AbstractTwenty-year-old Pinus radiata trees imported from New Zealand were investigated, and a comparison was made between the outerwood (rings 16–20) and corewood (rings 4–6) in terms of mechanical properties, anatomical characteristics, microfibril angle (MFA), relative crystallinity, crystallite size and lignin content to determine the relationship between their mechanical properties and microstructures. The results demonstrated that the mechanical properties of the Pinus radiata outerwood were significantly better than those of the corewood. The outerwood had a modulus of rupture (MOR) of 106 MPa, a modulus of elasticity (MOE) of 11.4 GPa, and compressive strength parallel to the grain of 38.7 MPa, and the MOR, MOE and compressive strength parallel to the grain of the corewood were 78.9 MPa, 7.12 GPa and 29.3 MPa, respectively. The observed microstructures of the Pinus radiata outerwood and corewood were different, mainly due to differences in cell wall thickness, MFA, and relative crystallinity. The double wall thickness of the tracheid cells of the corewood and outerwood were 3.65 and 5.02 µm, respectively. The MFA data indicated that the average MFA of the outerwood was 14.0°, which was smaller than that of the corewood (22.3°). With X-ray diffraction, the relative crystallinity of the corewood was determined to be 35.7%, while that of the outerwood was 40.2%. However, the crystallite size of the outerwood cell wall shows no obvious difference from that of the corewood. Imaging FTIR spectroscopy showed a slightly higher relative content of lignin in the cell wall of the outerwood. The correlation between the microstructures and mechanical properties showed that the corewood with a thin cell wall, large MFA and low relative crystallinity had poor mechanical properties, while the outerwood with a thicker tracheid, smaller MFA and higher relative crystallinity had better mechanical properties. This means that the MFA, relative crystallinity and cell wall thickness synergically affect the mechanical properties of Pinus radiata in different radial locations.
Anti-hypertensive drugs deprescribing: an updated systematic review of clinical trials
Authors: Crisafulli Salvatore , Luxi Nicoletta , Coppini Raffaele , Capuano Annalisa , Scavone Cristina , Zinzi Alessia , Vecchi Simona , Onder Graziano , Sultana Janet , Trifirò Gianluca 
Published: October 2021

Abstract
Background
Polypharmacy is defined as the prescription of at least 5 different medicines for therapeutic or prophylactic effect and is a serious issue among elderly patients, who are frequently affected by multi-morbidity. Deprescribing is one of the proposed approaches to reduce the number of administered drugs, by eliminating those that are inappropriately prescribed. The aim of this systematic review is to provide an updated and systematic assessment of the benefit-risk profile of deprescribing of anti-hypertensive drugs, which are among the most commonly used drugs.

Methods
MEDLINE, EMBASE and The Cochrane Library were searched for studies assessing the efficacy and safety of anti-hypertensive drugs deprescribing in the period between January, 12,016 and December, 312,019. The quality of randomized clinical trials (RCTs) was assessed using the GRADE approach for the evaluation of the main outcomes. The risk of bias assessment was carried out using the Cochrane risk-of-bias tool.

Results
Overall, two RCTs were identified. Despite summarized evidence was in favor of anti-hypertensive deprescribing, the overall risk of bias was rated as high for each RCT included. According to the GRADE approach, the overall quality of the RCTs included was moderate regarding the following outcomes: systolic blood pressure < 150 mmHg after 12 weeks of follow-up, quality of life, frailty and cardiovascular risk.

Conclusions
This updated systematic review of the efficacy and safety of anti-hypertensive treatment deprescribing found two recently published RCTs, in addition to the previous guideline of the National Institute for Health and Care Excellence (NICE). Evidence points towards non-inferiority of anti-hypertensive deprescribing as compared to treatment continuation, despite the quality of published studies is not high. High quality experimental studies are urgently needed to further assess the effect of deprescribing for this drug class in specific categories of patients.
A prospective cohort study providing insights for markers of adverse pregnancy outcome in older mothers
Authors: Lean Samantha C. , Jones Rebecca L. , Roberts Stephen A. , Heazell Alexander E. P. 
Published: October 2021

Abstract
Background
Advanced maternal age (≥35 years) is associated with increased rates of adverse pregnancy outcome. Better understanding of underlying pathophysiological processes may improve identification of older mothers who are at greatest risk. This study aimed to investigate changes in oxidative stress and inflammation in older women and identify clinical and biochemical predictors of adverse pregnancy outcome in older women.

Methods
The Manchester Advanced Maternal Age Study (MAMAS) was a multicentre, observational, prospective cohort study of 528 mothers. Participants were divided into three age groups for comparison 20–30 years (n = 154), 35–39 years (n = 222) and ≥ 40 years (n = 152). Demographic and medical data were collected along with maternal blood samples at 28 and 36 weeks’ gestation. Multivariable analysis was conducted to identify variables associated with adverse outcome, defined as one or more of: small for gestational age (< 10th centile), FGR (<5th centile), stillbirth, NICU admission, preterm birth < 37 weeks’ gestation or Apgar score < 7 at 5 min. Biomarkers of inflammation, oxidative stress and placental dysfunction were quantified in maternal serum. Univariate and multivariable logistic regression was used to identify associations with adverse fetal outcome.

Results
Maternal smoking was associated with adverse outcome irrespective of maternal age (Adjusted Odds Ratio (AOR) 4.22, 95% Confidence Interval (95%CI) 1.83, 9.75), whereas multiparity reduced the odds (AOR 0.54, 95% CI 0.33, 0.89). In uncomplicated pregnancies in older women, lower circulating anti-inflammatory IL-10, IL-RA and increased antioxidant capacity (TAC) were seen. In older mothers with adverse outcome, TAC and oxidative stress markers were increased and levels of maternal circulating placental hormones (hPL, PlGF and sFlt-1) were reduced (p < 0.05). However, these biomarkers only had modest predictive accuracy, with the largest area under the receiver operator characteristic (AUROC) of 0.74 for placental growth factor followed by TAC (AUROC = 0.69).

Conclusions
This study identified alterations in circulating inflammatory and oxidative stress markers in older women with adverse outcome providing preliminary evidence of mechanistic links. Further, larger studies are required to determine if these markers can be developed into a predictive model of an individual older woman’s risk of adverse pregnancy outcome, enabling a reduction in stillbirth rates whilst minimising unnecessary intervention.