bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the Predictive Power of the In-Training Examination for the Certification of Anesthesiologist Assistants
Authors: Grabovsky Irina , Henderek Jerusha J. , Luciw-Dubas Ulana A. , Pierce Brent , Campbell Soren , Monroe Katherine S. 
Published: June 2023

OBJECTIVES In-training examinations (ITEs) are a popular teaching tool for certification programs. This study examines the relationship between examinees’ performance on the National Commission for Certification of Anesthesiologist Assistants (NCCAA) ITE and the high-stakes NCCAA Certification Examination. METHODS We utilized a mixed-methods approach in our study. Before estimating the models for the predictive validity study, a series of interviews with program directors were conducted to discuss the role of the ITE in students’ education. Multiple linear regression analysis was then used to assess the strength of the relationship between the ITE and Certification Examination scores, while considering the percentage of program examinees completed in their anesthesiologist assistant program between their ITE and Certification Examination attempts. Logistic regression analysis was used to estimate the probability of passing the Certification Examination as a function of ITE score. RESULTS Interviews with program directors confirmed that the ITE provided a valuable testing experience for students and highlighted the areas where students need to focus. Moreover, both the ITE score and the percentage of the program between exams were deemed statistically significant predictors for Certification Examination scores. The logistic regression model indicated that higher scores on the ITE implied a higher probability of passing the Certification Examination. CONCLUSION This research demonstrated the high predictive validity of the ITE examination scores in predicting the Certification Examination outcomes. Together with the proportion of the program covered between exams, the variables explain a significant amount of variability in Certification Examination scores. The ITE feedback helped students assess their preparedness and better focus their studies for the high-stakes certification examination for the profession.
Otological Challenges in Patients With Non-Syndromic Cleft Lip and Palate: A Systematic Review
Authors: James Olutayo , Otoghile Bright , Adamson Olawale O. , Egbunah Uchenna P. , Sabo Vinishe Y. , Adekunle Adegbayi A. , Adeyemo Wasiu L. , Ladeinde Akinola L. , Ogunlewe Olugbenga M. 
Published: June 2023

Objectives: To identify the various otological challenges associated with non-syndromic orofacial clefts, how these problems affect quality of life of patients with orofacial clefts and find out the perspectives and current trends in the management of otological problems. Design: We conducted systematic searches for retrospective studies, cross-sectional studies, case-control studies, cohorts’ longitudinal studies and prospective controlled trials in Medline and Google scholar databases. Identified studies were retrieved and assessed for eligibility. Results: Thirty-five articles met all inclusion criteria and were selected for qualitative analysis. Twenty-one articles evaluated otological challenges associated with cleft lip and palate, 7 articles evaluated associated quality of life of patients with otological challenges and 9 articles evaluated management of otological challenges. Based on the results from this review, otological challenges including otitis media with effusion, conductive and sensorineural hearing loss are commonly associated with cleft. The result is a reduced quality of life due to their negative effects on intelligibility and eloquence of speech. They can however be managed by various palatoplasty procedures, rapid maxillary expansion, and use of various otological aids performed at an early age. Conclusion: The prevalence otological challenges in the cleft population are high and these issues require early management due to their possible effects on quality of life. Hence, there is need to incorporate ear care in the routine management of cleft lip and palate.
Antibody-mediated pathogenesis of chronic GVHD through DBY/HLA class II complexes and induction of a GVL effect
Authors: Umino Kento , Morita Kaoru , Ikeda Takashi , Kawaguchi Shin-ichiro , Nagayama Takashi , Ito Shoko , Minakata Daisuke , Ashizawa Masahiro , Yamamoto Chihiro , Hatano Kaoru , Sato Kazuya , Ohmine Ken , Fujiwara Shin-ichiro , Kimura Shun-ichi , Kako Shinichi , Doki Noriko , Ozawa Yukiyasu , Mori Yasuo , Eto Tetsuya , Hiramoto Nobuhiro , Nakamae Hirohisa , Kanda Junya , Ichinohe Tatsuo , Atsuta Yoshiko , Nakasone Hideki , Morishima Satoko , Kanda Yoshinobu 
Published: June 2023

Abstract
Chronic graft-versus-host disease (cGVHD) is a multiorgan syndrome with clinical features resembling those of autoimmune diseases. Thus, understanding commonalities in the pathophysiology of cGVHD and autoimmune diseases, such as the presence of disease-risk HLA alleles, is imperative for developing novel therapies against cGVHD. Alloantibodies against H-Y antigens encoded on the Y-chromosome are well-described risk factors for cGVHD in female-to-male transplantation. However, because H-Y antigens generally localize intracellularly in the male reproductive organs, how they emerge at affected organ levels remains elusive. Here, by analyzing nationwide registry data stratified per donor–recipient sex, we identified specific HLA class II alleles that contributed to susceptibility to male cGVHD after transplantation from HLA-identical female siblings (HLA-DRB1∗15:02: hazard ratio, 1.28; 95% confidence interval, 1.03-1.58; P = .025). Coexpression of HLA-DRB1∗15:02 efficiently transported full-length H-Y antigens, especially DBY, to the surface. The presence of alloantibodies against DBY/HLA class II complexes significantly predicted the occurrence of cGVHD (68.8% vs 31.7% at 1 year; P = .002). Notably, the ability of HLA class II molecules to transport and present DBY to alloantibodies was closely associated with the susceptibility of HLA class II alleles to cGVHD. DBY specifically colocalized with HLA class II molecules on the dermal vascular endothelium in cGVHD and provoked complement-dependent cytotoxicity. Moreover, these complexes were observed in some male leukemic cells. Altogether, these findings suggest that vascular endothelial cells facilitate alloantibody-mediated cGVHD and highlight that alloantibodies against DBY/HLA class II complexes could be common targets for cGVHD and a graft-versus-leukemia effect.
Final analysis of the CLL2-GIVe trial: obinutuzumab, ibrutinib, and venetoclax for untreated CLL with del(17p)/TP53mut
Authors: Huber Henriette , Tausch Eugen , Schneider Christof , Edenhofer Simone , von Tresckow Julia , Robrecht Sandra , Giza Adam , Zhang Can , Fürstenau Moritz , Dreger Peter , Ritgen Matthias , Illmer Thomas , Illert Anna Lena , Dürig Jan , Böttcher Sebastian , Niemann Carsten U. , Kneba Michael , Al-Sawaf Othman , Kreuzer Karl-Anton , Fink Anna-Maria , Fischer Kirsten , Döhner Hartmut , Hallek Michael , Eichhorst Barbara , Stilgenbauer Stephan 
Published: June 2023

Abstract
The final analysis of the open-label, multicenter phase 2 CLL2-GIVe trial shows response and tolerability of the triple combination of obinutuzumab, ibrutinib, and venetoclax (GIVe regimen) in 41 previously untreated patients with high-risk chronic lymphocytic leukemia (CLL) with del(17p) and/or TP53 mutation. Induction consisted of 6 cycles of GIVe; venetoclax and ibrutinib were continued up to cycle 12 as consolidation. Ibrutinib was given until cycle 15 or up to cycle 36 in patients not achieving a complete response and with detectable minimal residual disease. The primary end point was the complete remission rate at cycle 15, which was achieved at 58.5% (95% CI, 42.1-73.7; P &lt; .001). The last patient reached the end of the study in January 2022. After a median observation time of 38.4 months (range, 3.7-44.9), the 36-month progression-free survival was 79.9%, and the 36-month overall survival was 92.6%. Only 6 patients continued ibrutinib maintenance. Adverse events of concern were neutropenia (48.8%, grade ≥3) and infections (19.5%, grade ≥3). Cardiovascular toxicity grade 3 occurred as atrial fibrillation at a rate of 2.4% between cycles 1 and 12, as well as hypertension (4.9%) between cycles 1 and 6. The incidence of adverse events of any grade and grade ≥3 was highest during induction and decreased over time. Progressive disease was observed in 7 patients between cycles 27 and 42. In conclusion, the CLL2-GIVe regimen is a promising fixed-duration, first-line treatment for patients with high-risk CLL with a manageable safety profile.
Characterization of plywood made from heat-treated rubberwood veneers bonded with melamine urea formaldehyde resin
Authors: Chotikhun Aujchariya , Kittijaruwattana Jitralada , Lee Seng Hua , Salca Emilia-Adela , Arsyad Wa Ode Muliastuty , Hadi Yusuf Sudo , Neimsuwan Trairat , Hiziroglu Salim 
Published: June 2023

AbstractThe objective of the study is to evaluate the properties of the plywood made from rubberwood veneers thermally treated at various temperatures. Rotary-peeled rubberwood veneers were thermally treated at 160, 170, 180, and 190 °C under 1 bar pressure. 5-ply plywood panels were produced using melamine urea formaldehyde (MUF) resin as binder. Dimensional stability, i.e., water absorption (WA) and thickness swelling (TS) as well as mechanical properties of the plywood were assessed. The results demonstrated that the dimensional stability of the plywood made from thermally treated rubberwood veneers improved as indicated by lower WA and TS values. The reduction in WA and TS values increased along with treatment temperatures. Darkening in the plywood as a result of heat treatment was observed. Meanwhile, heat treatment at 170 °C and 180 °C resulted in plywood with the highest modulus of rupture (MOR), modulus of elasticity (MOE) and shear strength. However, beyond that temperature, the mechanical strength of the plywood started to decline. Based on the findings in this work it appears that heat treatment of rubberwood veneers at temperatures ranging from 160 to 180 °C could have a potential to improve overall properties of plywood panels.
Notch mediates the glycolytic switch via PI3K/Akt signaling to support embryonic development
Authors: Wang Heng , Liang Wenqi , Wang Xuyang , Zhan Yuchun , Wang Wence , Yang Lin , Zhu Yongwen 
Published: June 2023

Abstract
Background
Energy metabolism disorder or insufficient energy supply during incubation will affect the development and survival of avian embryos. Especially, β-oxidation could not provide the continuous necessary energy for avian embryonic development due to the increasing energy demand under hypoxic conditions during the mid–late embryonic stages. The role and mechanism of hypoxic glycolysis replacing β-oxidation as the main source of energy supply for avian embryonic development in the mid–late stages is unclear.

Results
Here, we found that in ovo injection with glycolysis inhibitor or γ-secretase inhibitor both decreased the hepatic glycolysis level and impaired goose embryonic development. Intriguingly, the blockade of Notch signaling is also accompanied by the inhibition of PI3K/Akt signaling in the embryonic primary hepatocytes and embryonic liver. Notably, the decreased glycolysis and impaired embryonic growth induced by the blockade of Notch signaling were restored by activation of PI3K/Akt signaling.

Conclusions
Notch signaling regulates a key glycolytic switch in a PI3K/Akt-dependent manner to supply energy for avian embryonic growth. Our study is the first to demonstrate the role of Notch signaling-induced glycolytic switching in embryonic development, and presents new insight into the energy supply patterns in embryogenesis under hypoxic conditions. In addition, it may also provide a natural hypoxia model for developmental biology studies such as immunology, genetics, virology, cancer, etc.

Graphical Abstract
An open protocol for modeling T Cell Clonotype repertoires using TCRβ CDR3 sequences
Authors: Gurun Burcu , Horton Wesley , Murugan Dhaarini , Zhu Biqing , Leyshock Patrick , Kumar Sushil , Byrne Katelyn T. , Vonderheide Robert H. , Margolin Adam A. , Mori Motomi , Spellman Paul T. , Coussens Lisa M. , Speed Terence P. 
Published: June 2023

AbstractT cell receptor repertoires can be profiled using next generation sequencing (NGS) to measure and monitor adaptive dynamical changes in response to disease and other perturbations. Genomic DNA-based bulk sequencing is cost-effective but necessitates multiplex target amplification using multiple primer pairs with highly variable amplification efficiencies. Here, we utilize an equimolar primer mixture and propose a single statistical normalization step that efficiently corrects for amplification bias post sequencing. Using samples analyzed by both our open protocol and a commercial solution, we show high concordance between bulk clonality metrics. This approach is an inexpensive and open-source alternative to commercial solutions.
Clonostachys rosea ‘omics profiling: identification of putative metabolite-gene associations mediating its in vitro antagonism against Fusarium graminearum
Authors: Bahadoor Adilah , Robinson Kelly A. , Loewen Michele C. , Demissie Zerihun A. 
Published: June 2023

Abstract
Background
Clonostachys rosea is an established biocontrol agent. Selected strains have either mycoparasitic activity against known pathogens (e.g. Fusarium species) and/or plant growth promoting activity on various crops. Here we report outcomes from a comparative ‘omics analysis leveraging a temporal variation in the in vitro antagonistic activities of C. rosea strains ACM941 and 88–710, toward understanding the molecular mechanisms underpinning mycoparasitism.

Results
Transcriptomic data highlighted specialized metabolism and membrane transport related genes as being significantly upregulated in ACM941 compared to 88–710 at a time point when the ACM941 strain had higher in vitro antagonistic activity than 88–710. In addition, high molecular weight specialized metabolites were differentially secreted by ACM941, with accumulation patterns of some metabolites matching the growth inhibition differences displayed by the exometabolites of the two strains. In an attempt to identify statistically relevant relationships between upregulated genes and differentially secreted metabolites, transcript and metabolomic abundance data were associated using IntLIM (Integration through Linear Modeling). Of several testable candidate associations, a putative C. rosea epidithiodiketopiperazine (ETP) gene cluster was identified as a prime candidate based on both co-regulation analysis and transcriptomic-metabolomic data association.

Conclusions
Although remaining to be validated functionally, these results suggest that a data integration approach may be useful for identification of potential biomarkers underlying functional divergence in C. rosea strains.
Comparative transcriptomic analysis of male and females in the dioecious weeds Amaranthus palmeri and Amaranthus tuberculatus
Authors: Bobadilla Lucas K. , Baek Yousoon , Tranel Patrick J. 
Published: June 2023

Abstract
Background
Waterhemp (Amaranthus tuberculatus (Moq.) Sauer) and Palmer amaranth (Amaranthus palmeri S. Wats.) are two dioecious and important weed species in the world that can rapidly evolve herbicide-resistance traits. Understanding these two species' dioecious and sex-determination mechanisms could open opportunities for new tools to control them. This study aims to identify the differential expression patterns between males and females in A. tuberculatus and A. palmeri. Multiple analyses, including differential expression, co-expression, and promoter analyses, used RNA-seq data from multiple tissue types to identify putative essential genes for sex determination in both dioecious species.

Results
Genes were identified as potential key players for sex determination in A. palmeri. Genes PPR247, WEX, and ACD6 were differentially expressed between the sexes and located at scaffold 20 within or near the male-specific Y (MSY) region. Multiple genes involved with flower development were co-expressed with these three genes. For A. tuberculatus, no differentially expressed gene was identified within the MSY region; however, multiple autosomal class B and C genes were identified as differentially expressed and possible candidate genes.

Conclusions
This is the first study comparing the global expression profile between males and females in dioecious weedy Amaranthus species. Results narrow down putative essential genes for sex-determination in A. palmeri and A. tuberculatus and also strengthen the hypothesis of two different evolutionary events for dioecy within the genus.
Transcriptome profiling reveals the genes involved in tuberous root expansion in Pueraria (Pueraria montana var. thomsonii)
Authors: Xufeng Xiao , Yuanfeng Hu , Ming Zhang , Shucheng Si , Haonan Zhou , Weifeng Zhu , Fei Ge , Caijun Wu , Shuying Fan 
Published: June 2023

Abstract
Background
Pueraria is a dry root commonly used in Traditional Chinese Medicine or as food and fodder, and tuberous root expansion is an important agronomic characteristic that influences its yield. However, no specific genes regulating tuberous root expansion in Pueraria have been identified. Therefore, we aimed to explore the expansion mechanism of Pueraria at six developmental stages (P1–P6), by profiling the tuberous roots of an annual local variety “Gange No.1” harvested at 105, 135, 165, 195, 225, and 255 days after transplanting.

Results
Observations of the tuberous root phenotype and cell microstructural morphology revealed that the P3 stage was a critical boundary point in the expansion process, which was preceded by a thickening diameter and yield gain rapidly of the tuberous roots, and followed by longitudinal elongation at both ends. A total of 17,441 differentially expressed genes (DEGs) were identified by comparing the P1 stage (unexpanded) against the P2–P6 stages (expanded) using transcriptome sequencing; 386 differential genes were shared across the six developmental stages. KEGG pathway enrichment analysis showed that the DEGs shared by P1 and P2–P6 stages were mainly involved in pathways related to the “cell wall and cell cycle”, “plant hormone signal transduction”, “sucrose and starch metabolism”, and “transcription factor (TF)”. The finding is consistent with the physiological data collected on changes in sugar, starch, and hormone contents. In addition, TFs including bHLHs, AP2s, ERFs, MYBs, WRKYs, and bZIPs were involved in cell differentiation, division, and expansion, which may relate to tuberous root expansion. The combination of KEGG and trend analyses revealed six essential candidate genes involved in tuberous root expansion; of them, CDC48, ARF, and EXP genes were significantly upregulated during tuberous root expansion while INV, EXT, and XTH genes were significantly downregulated.

Conclusion
Our findings provide new insights into the complex mechanisms of tuberous root expansion in Pueraria and candidate target genes, which can aid in increasing Pueraria yield.
Hospital disaster preparedness in sub-Saharan Africa: a systematic review of English literature
Authors: Farah Bashir , Pavlova Milena , Groot Wim 
Published: June 2023

AbstractBackgroundDisasters are increasing worldwide, with Sub-Saharan Africa (SSA) being one of the most prone regions. Hospitals play a key role in disasters. This study provides a systematic review of the evidence on disaster preparedness by hospitals in SSA countries based on English literature.MethodsA systematic literature review was conducted of articles published between January 2012 and July 2022. We searched PubMed, Elsevier, Science Direct, Google Scholar, the WHO depository library and CDC sites for English language publications. The key inclusion criteria were: publications should have been published in the above period, deal with hospital disaster preparedness in SSA, the full paper should have been available, and studies should have presented a comparison between hospitals and/or a single hospital.ResultsResults indicate improvements in disaster preparedness over time. However, health systems in SSA are generally considered vulnerable, and they find it difficult to adapt to changing health conditions. Inadequately skilled healthcare professionals, underfunding, poor knowledge, the absence of governance and leadership, lack of transparency and bureaucracy are the main preparedness barriers. Some countries are in an infancy stage of their health system development, while others are among the least developed health system in the world. Finally, a major barrier to disaster preparedness in SSA countries is the inability to collaborate in disaster response.ConclusionsHospital disaster preparedness is vulnerable in SSA countries. Thus, improvement of hospital disaster preparedness is highly needed.
Interpretation of active-control randomised trials: the case for a new analytical perspective involving averted events
Authors: Dunn David T. , Stirrup Oliver T. , McCormack Sheena , Glidden David V. 
Published: June 2023

AbstractActive-control trials, where an experimental treatment is compared with an established treatment, are performed when the inclusion of a placebo control group is deemed to be unethical. For time-to-event outcomes, the primary estimand is usually the rate ratio, or the closely-related hazard ratio, comparing the experimental group with the control group. In this article we describe major problems in the interpretation of this estimand, using examples from COVID-19 vaccine and HIV pre-exposure prophylaxis trials. In particular, when the control treatment is highly effective, the rate ratio may indicate that the experimental treatment is clearly statistically inferior even when it is worthwhile from a public health perspective. We argue that it is crucially important to consider averted events as well as observed events in the interpretation of active-control trials. An alternative metric that incorporates this information, the averted events ratio, is proposed and exemplified. Its interpretation is simple and conceptually appealing, namely the proportion of events that would be averted by using the experimental treatment rather than the control treatment. The averted events ratio cannot be directly estimated from the active-control trial, and requires an additional assumption about either: (a) the incidence that would have been observed in a hypothetical placebo arm (the counterfactual incidence) or (b) the efficacy of the control treatment (relative to no treatment) that pertained in the active-control trial. Although estimation of these parameters is not straightforward, this must be attempted in order to draw rational inferences. To date, this method has been applied only within HIV prevention research, but has wider applicability to treatment trials and other disease areas.