bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dolutegravir Impairs Stem Cell-Based 3D Morphogenesis Models in a Manner Dependent on Dose and Timing of Exposure: An Implication for Its Developmental Toxicity
Authors: Kirkwood-Johnson Lauren , Katayama Nana , Marikawa Yusuke 
Published: September 2021

AbstractDolutegravir (DTG) is an antiretroviral drug of the integrase strand transfer inhibitor (INSTI) class used to treat human immunodeficiency virus infection. It is the recommended first-line regimen for most people, including women of childbearing age. However, some human and animal studies have suggested that DTG causes birth defects, although its developmental toxicity remains controversial. Here, we investigated the adverse effects of DTG using pluripotent stem cell-based in vitro morphogenesis models that have previously been validated as effective tools to assess the developmental toxicity of various chemicals. DTG diminished the growth and axial elongation of the morphogenesis model of mouse pluripotent stem cells at exposures of 2 μM and above in a concentration-dependent manner. Concomitantly, DTG altered the expression profiles of developmental regulator genes involved in embryonic patterning. The adverse effects were observed when the morphogenesis model was exposed to DTG at early stages of development, but not at later stages. The potency and molecular impact of DTG on the morphogenesis model were distinct from other INSTIs. Last, DTG altered the growth and gene expression profiles of the morphogenesis model of human embryonic stem cells at 1 μM and above. These studies demonstrate that DTG impairs morphological and molecular aspects of the in vitro morphogenesis models in a manner dependent on dose and timing of exposure through mechanisms that are unrelated to its action as an INSTI. This finding will be useful for interpreting the conflicting outcomes regarding the developmental toxicity of DTG in human and animal studies.
Small understorey trees have greater capacity than canopy trees to adjust hydraulic traits following prolonged experimental drought in a tropical forest
Authors: Giles A L , Rowland L , Bittencourt P R L , Bartholomew D C , Coughlin I , Costa P B , Domingues T , Miatto R C , Barros F V , Ferreira L V , Groenendijk P , Oliveira A A R , da Costa A C L , Meir P , Mencuccini M , Oliveira R S 
Published: September 2021

Abstract
Future climate change predictions for tropical forests highlight increased frequency and intensity of extreme drought events. However, it remains unclear whether large and small trees have differential strategies to tolerate drought due to the different niches they occupy. The future of tropical forests is ultimately dependent on the capacity of small trees (&lt;10 cm in diameter) to adjust their hydraulic system to tolerate drought. To address this question, we evaluated whether the drought tolerance of neotropical small trees can adjust to experimental water stress and was different from tall trees. We measured multiple drought resistance-related hydraulic traits across nine common neotropical genera at the world’s longest-running tropical forest throughfall-exclusion experiment and compared their responses with surviving large canopy trees. Small understorey trees in both the control and the throughfall-exclusion treatment had lower minimum stomatal conductance and maximum hydraulic leaf-specific conductivity relative to large trees of the same genera, as well as a greater hydraulic safety margin (HSM), percentage loss of conductivity and embolism resistance, demonstrating that they occupy a distinct hydraulic niche. Surprisingly, in response to the drought treatment, small trees increased specific hydraulic conductivity by 56.3% and leaf:sapwood area ratio by 45.6%. The greater HSM of small understorey trees relative to large canopy trees likely enabled them to adjust other aspects of their hydraulic systems to increase hydraulic conductivity and take advantage of increases in light availability in the understorey resulting from the drought-induced mortality of canopy trees. Our results demonstrate that differences in hydraulic strategies between small understorey and large canopy trees drive hydraulic niche segregation. Small understorey trees can adjust their hydraulic systems in response to changes in water and light availability, indicating that natural regeneration of tropical forests following long-term drought may be possible.
5Religion and Representation
Authors: Rzepa Joanna 
Published: September 2021

AbstractIn recent years, the relationship between religion and representation has been examined with particular intensity in the field of modernist studies, to which all books reviewed in this chapter have contributed. It is telling that three of them are devoted to Virginia Woolf, whose firm rejection of patriarchal Christianity and the established church has for years been considered a prime example of modernism’s hostility to religion. New scholarship on Woolf, religion, and spirituality offers a much more nuanced view of her engagement with Christian culture and illustrates the wealth of new methodological developments in the field of modernist studies. The review opens with a discussion of the recent religious turn in modernist studies, situating it within the expansion of the field connected to the emergence of the new modernist studies. Subsequently, it examines four new books that contribute to scholarship on modernism and religion. The chapter is divided into five sections: 1. The New Modernist Studies and Religion; 2. Jane de Gay, Virginia Woolf and Christian Culture; 3. Stephanie Paulsell, Religion Around Virginia Woolf; 4. Religion, Secularism, and the Spiritual Paths of Virginia Woolf, edited by Kristina K. Groover; 5. Martin Lockerd, Decadent Catholicism and the Making of Modernism. The books reviewed illustrate the scope and depth of new research into modernism and religion, offering a fresh critical perspective that challenges the widely accepted view of modernism as a purely secular movement.
XVII New Literatures
Authors: Batra Kanika , Lorre-Johnston Christine , Manzo Kerry , McNeill Dougal , Miller Benjamin , Naruse Cheryl Narumi , Niblett Michael , Sharrad Paul , Uraizee Joya , Zarranz Libe Garcia 
Published: September 2021

AbstractThis chapter has seven sections: 1. Africa; 2. Australia; 3. Canada; 4. The Caribbean; 5. South Asia: The Indian Subcontinent and Sri Lanka; 6. New Zealand and Pacific; 7. Southeast Asia. Section 1 is by Kanika Batra, Kerry Manzo, and Joya Uraizee; coverage of West Africa will resume in 2022; section 2 is by Benjamin Miller and Paul Sharrad; section 3 is by Christine Lorre-Johnston and Libe García Zarranz; section 4 is by Michael Niblett; section 5 will resume in 2022; section 6 is by Dougal McNeill; section 7 is by Cheryl Narumi Naruse.
The Utility of the Hyperinlet View in Posterior Fixation of Pelvic Ring Injuries
Authors: Gosselin Michelle M. , Dennis Garret S. , Gary Joshua L. 
Published: September 2021

Summary:
Percutaneous pelvic fixation has evolved into a widely used, safe, and effective treatment option in the management of pelvic ring injuries. Proper preoperative and intraoperative radiographic evaluation of these injuries is critical to ensure safe placement of fixation of the pelvis. Traditional intraoperative views for posterior pelvic ring fixation include the pelvic inlet and outlet views. We propose that the intraoperative use of a hyperinlet view, which uses additional cranial tilt relative to the traditional inlet view, is helpful to better delineate the spinal canal and thereby better define the posterior limit of the osseous fixation pathway of the upper sacral segments. This study illustrates the use of this novel radiographic view and presents a patient cohort in which it was effectively used.
Smoking Is Associated With Lower Satisfaction in Nondiabetic Patients Undergoing Minimally Invasive Single-level Transforaminal Lumbar Interbody Fusion
Authors: Gatot Cheryl , Liow Ming Han Lincoln , Goh Graham S. , Mohan Niraj , Yongqiang Chen Jerry , Ling Zhixing Marcus , Soh Reuben C.C. , Yue Wai-Mun , Guo Chang-Ming , Tan Seang-Beng , Chen John Li-Tat 
Published: September 2021

Study Design:This was a retrospective review of prospectively collected registry data.Objective:The objective of this study was to investigate the effect of smoking on 2 years postoperative functional outcomes, satisfaction, and radiologic fusion in nondiabetic patients undergoing minimally invasive transforaminal lumbar interbody fusion (TLIF) for degenerative spine conditions.Summary of Background Data:There is conflicting data on the effect of smoking on long-term functional outcomes following lumbar fusion. Moreover, there remains a paucity of literature on the influence of smoking within the field of minimally invasive spine surgery.Methods:Prospectively collected registry data of nondiabetic patients who underwent primary single-level minimally invasive TLIF in a single institution was reviewed. Patients were stratified based on smoking history. All patients were assessed preoperatively and postoperatively using the Numerical Pain Rating Scale for back pain and leg pain, Oswestry Disability Index, Short-Form 36 Physical and Mental Component Scores. Satisfaction was assessed using the North American Spine Society questionnaire. Radiographic fusion rates were compared.Results:In total, 187 patients were included, of which 162 were nonsmokers, and 25 had a positive smoking history. In our multivariate analysis, smoking history was insignificant in predicting for minimal clinically important difference attainment rates in Physical Component Score and fusion grading outcomes. However, in terms of satisfaction score, positive smoking history remained a significant predictor (odds ratio=4.7, 95% confidence interval: 1.10–20.09,P=0.036).Conclusions:Nondiabetic patients with a positive smoking history had lower satisfaction scores but comparable functional outcomes and radiologic fusion 2 years after single-level TLIF. Thorough preoperative counseling and smoking cessation advice may help to improve patient satisfaction following minimally invasive spine surgery.Level of Evidence:Level III—nonrandomized cohort study.
Disseminated Coccidioidomycosis as the First Presentation of a C-Terminal NFKB2 Pathogenic Variant: A Case Report and Review of the Literature
Authors: Pérez Cavazos Samantha , De la Cruz Cruz Rodrigo A. , Castillo Bejarano José Iván , Vaquera Aparicio Denisse Natalie , Mascareñas de los Santos Abiel Homero , Zárate Hernández Mariá del Carmen 
Published: September 2021

Introduction:
Although most cases of coccidioidomycosis are subclinical or self-limited respiratory disease, 1% lead to extrathoracic dissemination and become fatal, especially in patients with an associated immunodeficiency. Up to 30%–50% of patients with defects in cell-mediated immunity, those with AIDS and recipients of solid-organ transplants, may develop disseminated coccidioidomycosis (DC). Within the primary immunodeficiencies, an uncommon group is caused by C-terminal NFKB2 pathogenic variants.

Materials and Methods:
We performed a literature search of core databases. Written informed consent for the study and for publication was obtained.

Case Presentation:
A 7-year-old Mexican girl, eldest of 3 sisters, no relevant family history, and a history of recurrent upper respiratory infections and alopecia totalis was admitted with DC involving pulmonary, soft tissue, skin, bone and joint compromise. The immunodeficiency assessment showed low IgM and NK cells. We found an NFKB2 de novo heterozygous nonsense mutation of c.2611C>T (p.Gln871*). She was treated with liposomal amphotericin B and itraconazole with surgical debridement. The clinical phenotype of this primary immunodeficiency is characterized by antibody deficiency and associated broncho-pulmonary predisposition to infection, but moreover also opportunistic infections and autoimmunity, most recognizable alopecia and adrenocorticotropic hormone-deficiency. After 1 year of her discharge, she continues under surveillance with antifungal therapy with itraconazole and replacement intravenous immunoglobulin until today

Conclusion:
This is the first case report of DC in a patient with an NFKB2 pathogenic variant and it illustrates the importance of screening for primary immunodeficiencies in patients with disseminated fungal infections.
Machine Learning Used to Compare the Diagnostic Accuracy of Risk Factors, Clinical Signs and Biomarkers and to Develop a New Prediction Model for Neonatal Early-onset Sepsis
Authors: Stocker Martin , Daunhawer Imant , van Herk Wendy , el Helou Salhab , Dutta Sourabh , Schuerman Frank A. B. A. , van den Tooren-de Groot Rita K. , Wieringa Jantien W. , Janota Jan , van der Meer-Kappelle Laura H. , Moonen Rob , Sie Sintha D. , de Vries Esther , Donker Albertine E. , Zimmerman Urs , Schlapbach Luregn J. , de Mol Amerik C. , Hoffmann-Haringsma Angelique , Roy Madan , Tomaske Maren , Kornelisse René F. , van Gijsel Juliette , Plötz Frans B. , Wellmann Sven , Achten Niek B. , Lehnick Dirk , van Rossum Annemarie M. C. , Vogt Julia E. 
Published: September 2021

Background:
Current strategies for risk stratification and prediction of neonatal early-onset sepsis (EOS) are inefficient and lack diagnostic performance. The aim of this study was to use machine learning to analyze the diagnostic accuracy of risk factors (RFs), clinical signs and biomarkers and to develop a prediction model for culture-proven EOS. We hypothesized that the contribution to diagnostic accuracy of biomarkers is higher than of RFs or clinical signs.

Study Design:
Secondary analysis of the prospective international multicenter NeoPInS study. Neonates born after completed 34 weeks of gestation with antibiotic therapy due to suspected EOS within the first 72 hours of life participated. Primary outcome was defined as predictive performance for culture-proven EOS with variables known at the start of antibiotic therapy. Machine learning was used in form of a random forest classifier.

Results:
One thousand six hundred eighty-five neonates treated for suspected infection were analyzed. Biomarkers were superior to clinical signs and RFs for prediction of culture-proven EOS. C-reactive protein and white blood cells were most important for the prediction of the culture result. Our full model achieved an area-under-the-receiver-operating-characteristic-curve of 83.41% (±8.8%) and an area-under-the-precision-recall-curve of 28.42% (±11.5%). The predictive performance of the model with RFs alone was comparable with random.

Conclusions:
Biomarkers have to be considered in algorithms for the management of neonates suspected of EOS. A 2-step approach with a screening tool for all neonates in combination with our model in the preselected population with an increased risk for EOS may have the potential to reduce the start of unnecessary antibiotics.
Bronchoscopy in Patients With Known or Suspected COVID-19
Authors: Cumbo-Nacheli Gustavo , Colt Henri , Agrawal Abhinav , Cicenia Joseph , Corbetta Lorenzo , Goel Akhil D. , Goga Ameena , Lee Hans J. , Murgu Septimiu , Pannu Jasleen , Senitko Michal , Tarantini Francesco , Vujacich Patricia , Williamson Jonathan , Yap Elaine , Lentz Robert J. 
Published: September 2021

Background:
Amid the Coronavirus Disease 2019 (COVID-19) pandemic, the benefits and risks of bronchoscopy remain uncertain. This study was designed to characterize bronchoscopy-related practice patterns, diagnostic yields, and adverse events involving patients with known or suspected COVID-19.

Methods:
An online survey tool retrospectively queried bronchoscopists about their experiences with patients with known or suspected COVID-19 between March 20 and August 20, 2020. Collected data comprised the Global Pandemic SARS-CoV-2 Bronchoscopy Database (GPS-BD). All bronchoscopists and patients were anonymous with no direct investigator-to-respondent contact.

Results:
Bronchoscopy procedures involving 289 patients from 26 countries were analyzed. One-half of patients had known COVID-19. Most (82%) had at least 1 pre-existing comorbidity, 80% had at least 1 organ failure, 51% were critically ill, and 37% were intubated at the time of the procedure. Bronchoscopy was performed with diagnostic intent in 166 (57%) patients, yielding a diagnosis in 86 (52%). and management changes in 80 (48%). Bronchoscopy was performed with therapeutic intent in 71 (25%) patients, mostly for secretion clearance (87%). Complications attributed to bronchoscopy or significant clinical decline within 12 hours of the procedure occurred in 24 (8%) cases, with 1 death.

Conclusion:
Results from this international database provide a widely generalizable characterization of the benefits and risks of bronchoscopy in patients with known or suspected COVID-19. Bronchoscopy in this setting has reasonable clinical benefit, with diagnosis and/or management change resulting from about half of the diagnostic cases. However, it is not without risk, especially in patients with limited physiological reserve.
Increased FIO2 influences SvO2 interpretation and accuracy of Fick-based cardiac output assessment in cardiac surgery patients
Authors: Lin Sheng-Yi , Chang Feng-Cheng , Lin Jr-Rung , Chou An-Hsun , Tsai Yung-Fong , Liao Chia-Chih , Tsai Hsin-I. , Chen Chun-Yu 
Published: September 2021

Abstract

Introduction:
The study aimed to reveal how the fraction of inspired oxygen (FIO2) affected the value of mixed venous oxygen saturation (SvO2) and the accuracy of Fick-equation-based cardiac output (Fick-CO).

Methods:
Forty two adult patients who underwent elective cardiac surgery were enrolled and randomly divided into 2 groups: FIO2 < 0.7 or >0.85. Under stable general anesthesia, thermodilution-derived cardiac output (TD-CO), SvO2, venous partial pressure of oxygen, hemoglobin, arterial oxygen saturation, arterial partial pressure of oxygen, and blood pH levels were recorded before surgical incision.

Results:
Significant differences in FIO2 values were observed between the 2 groups (0.56 ± 0.08 in the <70% group and 0.92 ± 0.03 in the >0.85 group; P < .001). The increasing FIO2 values lead to increases in SvO2, venous partial pressure of oxygen, and arterial partial pressure of oxygen, with little effects on cardiac output and hemoglobin levels. When comparing to TD-CO, the calculated Fick-CO in both groups had moderate Pearson correlations and similar linear regression results. Although the FIO2 <0.7 group presented a less mean bias and a smaller limits of agreement, neither group met the percentage error criteria of <30% in Bland-Altman analysis.

Conclusion:
Increased FIO2 may influence the interpretation of SvO2 and the exacerbation of Fick-CO estimation, which could affect clinical management.

Trial Registration:
ClinicalTrials.gov ID number: NCT04265924, retrospectively registered (Date of registration: February 9, 2020).
Neuron - specific enolase predicts the prognosis in advanced small cell lung cancer patients treated with first-line PD-1/PD-L1 inhibitors
Authors: Li Lingling , Zhang Zhibo , Hu Yi 
Published: September 2021

Abstract
There has been no effective biomarker for small cell lung cancer (SCLC) patients with first-line immune checkpoint inhibitors (ICIs) treatment. The predictive value of neuron-specific enolase (NSE) in this cohort remains unclear.
The medical records of 254 consecutive SCLC patients receiving programmed cell death receptor-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors were compiled from January 2015 to October 2020 in Chinese PLA General Hospital. Survival analysis was performed to explore the prognostic role of NSE at baseline and 3 weeks post treatment.
One hundred two advanced SCLC patients treated with first-line PD-1/PD-L1 inhibitors were enrolled in this study. Normal baseline NSE levels were correlated with significantly prolonged progression-free survival (PFS, median: 8.7 vs 4.7 months, P = .006) and overall survival (OS, median: 23.8 vs 15.2 months, P = .014) compared with elevated baseline NSE levels, so as for normal NSE levels at 3 weeks with prolonged PFS (median PFS: 8.4 vs 4.5 months, P = .0002) and OS (median OS: 23.3 vs 7.4 months, P < .0001). Intriguingly, elevated NSE levels at 3 weeks were associated with shorter PFS (median PFS: 4.5 vs 5.8 months, P = .04) and OS (median OS: 5.5 vs 14.7 months, P < .0001) compared with normal NSE levels in the elevated baseline NSE subgroup. Most subgroup analyses stratified by clinical characteristics confirmed the prognostic value of baseline NSE level.
Elevated NSE levels at baseline and 3 weeks were associated with worse prognosis in advanced SCLC patients receiving first-line ICIs treatment. NSE level might be applied as a useful prognostic tool for SCLC patients with immunotherapy.
Clinical efficacy and safety of Huachansu injection combination with platinum-based chemotherapy for advanced non-small cell lung cancer
Authors: Tan Xinmei , Liang Xueyan , Xi Jiaxi , Guo Sitong , Meng Mingyu , Chen Xiaoyu , Li Yan 
Published: September 2021

Abstract

Background:
Huachansu injection (HCS) is a widely used traditional Chinese medicine for advanced non-small cell lung cancer (NSCLC) to alleviate the adverse drug reactions (ADRs) and enhance the clinical efficacy of chemotherapy.

Objective:
To evaluate the efficacy and safety of HCS as an adjunctive treatment to platinum-based chemotherapy (PBC) for advanced NSCLC.

Methods:
A systematic review and meta-analysis were conducted according to PRISMA guidelines. A total of nine databases were searched to select randomized controlled trials (RCTs) of HCS plus PBC to treat NSCLC from inception to October 10, 2020. RCTs on HCS plus PBC vs PBC alone for advanced NSCLC were included. Dichotomous data were pooled as risk ratio (RR) with 95% confidence intervals. RCTs compared to HCS plus PBC vs PBC alone were included. Primary outcomes were objective response rate (ORR) and disease control rate (DCR), and secondary outcomes were survival rate, quality of life (QOL), and adverse drug reactions (ADRs). GRADE software was used to access the quality of evidence.

Results:
A total of 32 RCTs, including 2753 patients, were included. Compared to PBC alone, HCS plus PBC improved the ORR, DCR, 1- and 2-year survival rates, and QOL and alleviated neutropenia, thrombocytopenia, nausea, vomiting, anemia, liver injury, renal injury, and alopecia.

Conclusions:
Compared to PBC alone, HCS plus PBC improved the clinical efficacy and alleviated the ADRs in advanced NSCLC patients. Considering the limitations of the included RCTs, high-quality trials with longer follow-ups are needed to further confirm the results.