bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in cardiorespiratory function and fatigue following 12 weeks of exercise training in women with systemic lupus erythematosus: a pilot study
Authors: Hasni Sarfaraz , Feng Li Rebekah , Chapman Marquis , Gupta Sarthak , Ahmad Anam , Munday Adam , Mazhar Mir Ali , Li Xiaobai , Lu Shajia , Tsai Wanxia Li , Gadina Massimo , Davis Michael , Chu Jun , Manna Zerai , Nakabo Shuichiro , Kaplan Mariana J , Saligan Leorey , Keyser Randall , Chan Leighton , Chin Lisa M K 
Published: October 2022

ObjectiveIn patients with systemic lupus erythematosus (SLE), fatigue is a debilitating symptom with poorly understood pathophysiology. Cardiorespiratory dysfunction has been hypothesised as a contributor to SLE-fatigue. The purpose of this exploratory study was to examine changes in cardiorespiratory function, following an exercise training programme in women with SLE, together with patient reported outcomes and other pathophysiological measures that may underlie SLE-fatigue.MethodsSixteen women with SLE and fatigue (Fatigue Severity Scale (FSS) ≥3) were enrolled in a supervised aerobic exercise training programme of vigorous intensity. The primary outcome was time to reach anaerobic threshold (AT-Time) during a cardiopulmonary exercise test (CPET). Secondary outcomes included changes in the 10-minute walk test (10MWT), FSS scores and the Patient Reported Outcomes Measurement Information System (PROMIS-57) survey. Mitochondrial function was assessed by the oxygen consumption rate (OCR)/extracellular acidification rate (ECAR) metabolic potential ratio.ResultsFollowing 12 weeks of exercise training, AT-Time increased by 93±82 (mean±SD) s (p<0.001), 10MWT increased by 84±66 m (p<0.001) and peak oxygen uptake (VO2) increased by 1.4±2.0 mL/kg/min (p=0.013). There were improvements in FSS score (−1.4±1.0, p<0.0001) and in most of the PROMIS-57 domains. The decrease in FSS scores correlated with an increase in the OCR/ECAR ratio (Pearson’s correlation r=-0.59, p=0.03). A subset of subjects (9/15) had significant reduction in their Interferon Stimulated Genes (ISG) (p=0.007) accompanied by a significant increase in the OCR/ECAR ratio (p=0.013).ConclusionsCardiorespiratory function was improved in concomitance with reductions in fatigue following a 12-week aerobic exercise programme. The reduction in fatigue scores correlated with improvements in mitochondrial function.
Incidence, predictors and clinical implications of new renal impairment following percutaneous coronary intervention
Authors: Wong Nathan , Dinh Diem T , Brennan Angela , Batchelor Riley , Duffy Stephen J , Shaw James A , Chan William , Layland Jamie , van Gaal William J , Reid Christopher M , Liew Danny , Stub Dion 
Published: October 2022

BackgroundRenal impairment post-percutaneous coronary intervention (post-PCI) is a well-described adverse effect following the administration of contrast media. Within a large cohort of registry patients, we aimed to explore the incidence, predictors and clinical outcomes of renal impairment post-PCI.MethodsThe Victorian Cardiac Outcomes Registry is an Australian state-based clinical quality registry focusing on collecting data from all PCI capable centres. Data from 36 970 consecutive PCI cases performed between 2014 and 2018 were analysed. Patients were separated into three groups based on post-procedure creatinine levels (new renal impairment (NRI), defined as an absolute rise in serum creatinine>44.2 µmol/L or>25% of baseline creatinine; new renal impairment requiring dialysis (NDR), defined as worsening renal failure that necessitated a new requirement for renal dialysis; no NRI). Multivariate logistic regression analysis was performed to investigate the impact of NRI and NDR on clinical outcomes.Results3.1% (n=1134) of patients developed NRI, with an additional 0.6% (n=225) requiring dialysis. 96.3% (n=35 611) of patients did not develop NRI. Those who developed renal impairment were more comorbid, with higher rates of diabetes (22% vs 38% vs 38%, p<0.001), peripheral vascular disease (3.4% vs 8.2% vs 11%, p<0.001), chronic kidney disease (19% vs 49.7% vs 54.2%) and severe left ventricular dysfunction (5% vs 22% vs 40%, p<0.001). Multivariable analysis found that when compared with the no NRI group, those in the combined NRI/NDR group were at a greater risk of 30-day mortality (OR 4.77; 95% CI 3.89 to 5.86, p<0.001) and 30-day major adverse cardiac events (OR 3.72; 95% CI 3.15 to 4.39, p<0.001).ConclusionsNRI post-PCI remains a common occurrence, especially among comorbid patients, and is associated with a significantly increased morbidity and mortality risk.
Cancer survivor inspiratory muscle training: systematic review and Bayesian meta-analysis
Authors: Tórtola-Navarro Aida , Gallardo-Gómez Daniel , Álvarez-Barbosa Francisco , Salazar-Martínez Eduardo 
Published: October 2022

BackgroundThe long-term impact of cancer treatment is associated with respiratory dysfunction and physical fitness impairment. Although inspiratory muscle training (IMT) has been shown as an effective exercise therapy in cancer survivors, there is no evidence on the optimal dose, application moment nor specific population effects of this intervention. The main objective of this meta-analysis is to analyse the effects of IMT on pulmonary function, physical fitness and quality of life (QoL) in cancer survivors.MethodsThis systematic review and meta-analysis was preregistered in the International Prospective Register of Systematic Reviews (PROSPERO) register and conducted according to the Preferred Reporting for Systematic Reviews and Meta-analysis statement. We used a Bayesian multilevel random-effects meta-analysis model to pool the data. Multilevel metaregression models were used to examine the conditional effects of our covariates. Convergence and model fit were evaluated through specific model parameters. Sensitivity analyses removing influential cases and using a frequentist approach were carried out.ResultsPooled data showed that IMT intervention is effective to improve pulmonary function (standardised mean difference=0.53, 95% credible interval 0.13 to 0.94, SE=0.19). However, IMT did not present statistically significant results on physical fitness and QoL. Metaregression analyses found that the type of cancer, the moment of application and the evaluation tool used had significant moderation effects on pulmonary function.ConclusionIMT could be an important part in the management of side effects suffered by cancer survivors. Considering the current evidence, this intervention is highly recommended in patients diagnosed with oesophageal and lung cancers. IMT may provide superior benefits before the biological treatment and after the surgery.PROSPERO registration number304909.
Comparative study of clinicians’ and family members’ perceptions of patients’ end-of-life experiences
Authors: Suzuki Kozue , Morita Tatsuya , Mori Masanori , Azuma Yukari , Funaki Hiromi , Amano Koji , Imai Kengo , Tanaka Keiko , Kizawa Yoshiyuki , Tsuneto Satoru , Shima Yasuo , Masukawa Kento , Miyashita Mitsunori 
Published: October 2022

ObjectiveEnd-of-life experiences (ELEs), such as deathbed visions (DBVs), have been reported worldwide. However, ELEs have rarely been discussed in clinical practice, possibly because of the different perceptions of ELEs among clinicians and families. Therefore, this study aimed to investigate the differences in perception regarding ELEs, especially DBVs, between clinicians and families.MethodsWe conducted a multicentre, prospective and observational study with patients with cancer. After the patients’ death, clinicians recorded their perceptions of patients’ ELEs during the palliative care unit admission, and bereaved families responded to a questionnaire about ELEs. The primary outcome was the frequency and concordance of DBVs from the perspective of bereaved family members and clinicians. The second outcome was each group’s frequency of terminal lucidity and terminal coincidence.ResultsThe study included 443 patients. DBVs were reported more frequently by family members than clinicians (14.0% vs 2.7%, p<0.001). Among family members, terminal lucidity and terminal coincidence were observed at 7% and 7.9%, respectively, while only one case each was reported by clinicians.ConclusionsClinicians and family members may perceive ELEs differently. Enabling patients and their families to talk about ELEs would assist in optimising grief care.
Loneliness and resilience are associated with nutrition risk after the first wave of COVID-19 in community-dwelling older Canadians
Authors: Wei Cindy , Beauchamp Marla K. , Vrkljan Brenda , Vesnaver Elisabeth , Giangregorio Lora , Macedo Luciana G. , Keller Heather H. 
Published: October 2022

Nutrition risk is linked to hospitalization, frailty, depression, and death. Loneliness during the coronavirus disease 2019 (COVID-19) pandemic may have heightened nutrition risk. We sought to determine prevalence of high nutrition risk and whether loneliness, mental health, and assistance with meal preparation/delivery were associated with risk in community-dwelling older adults (65+ years) after the first wave of COVID-19 in association analyses and when adjusting for meaningful covariates. Data were collected from 12 May 2020 to 19 August 2020. Descriptive statistics, association analyses, and linear regression analyses were conducted. For our total sample of 272 participants (78 ± 7.3 years old, 70% female), the median Seniors in the Community: Risk evaluation for Eating and Nutrition (SCREEN-8) score (nutrition risk) was 35 [1st quartile, 3rd quartile: 29, 40], and 64% were at high risk (SCREEN-8 < 38). Fifteen percent felt lonely two or more days a week. Loneliness and meal assistance were associated with high nutrition risk in association analyses. In multivariable analyses adjusting for other lifestyle factors, loneliness was negatively associated with SCREEN-8 scores (−2.92, 95% confidence interval [−5.51, −0.34]), as was smoking (−3.63, [−7.07, −0.19]). Higher SCREEN-8 scores were associated with higher education (2.71, [0.76, 4.66]), living with others (3.17, [1.35, 4.99]), higher self-reported health (0.11, [0.05, 0.16]), and resilience (1.28, [0.04, 2.52]). Loneliness, but not mental health and meal assistance, was associated with nutrition risk in older adults after the first wave of COVID-19. Future research should consider longitudinal associations among loneliness, resilience, and nutrition.
Epigenome-Wide Study Identifies Epigenetic Outliers in Normal Mucosa of Patients with Colorectal Cancer
Authors: Ghosh Jayashri , Schultz Bryant M. , Chan Joe , Wultsch Claudia , Singh Rajveer , Shureiqi Imad , Chow Stephanie , Doymaz Ahmet , Varriano Sophia , Driscoll Melissa , Muse Jennifer , Kleiman Frida E. , Krampis Konstantinos , Issa Jean-Pierre J. , Sapienza Carmen 
Published: October 2022

AbstractNongenetic predisposition to colorectal cancer continues to be difficult to measure precisely, hampering efforts in targeted prevention and screening. Epigenetic changes in the normal mucosa of patients with colorectal cancer can serve as a tool in predicting colorectal cancer outcomes. We identified epigenetic changes affecting the normal mucosa of patients with colorectal cancer. DNA methylation profiling on normal colon mucosa from 77 patients with colorectal cancer and 68 controls identified a distinct subgroup of normally-appearing mucosa with markedly disrupted DNA methylation at a large number of CpGs, termed as “Outlier Methylation Phenotype” (OMP) and are present in 15 of 77 patients with cancer versus 0 of 68 controls (P &lt; 0.001). Similar findings were also seen in publicly available datasets. Comparison of normal colon mucosa transcription profiles of patients with OMP cancer with those of patients with non-OMP cancer indicates genes whose promoters are hypermethylated in the OMP patients are also transcriptionally downregulated, and that many of the genes most affected are involved in interactions between epithelial cells, the mucus layer, and the microbiome. Analysis of 16S rRNA profiles suggests that normal colon mucosa of OMPs are enriched in bacterial genera associated with colorectal cancer risk, advanced tumor stage, chronic intestinal inflammation, malignant transformation, nosocomial infections, and KRAS mutations. In conclusion, our study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Prospective studies are needed to determine whether OMP could serve as a biomarker for an elevated epigenetic risk for colorectal cancer development.Prevention Relevance:Our study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Identification of OMPs in healthy controls and patients with colorectal cancer will lead to prevention and better prognosis, respectively.
TP53-Mutated Myelodysplastic Syndrome and Acute Myeloid Leukemia: Biology, Current Therapy, and Future Directions
Authors: Daver Naval G. , Maiti Abhishek , Kadia Tapan M. , Vyas Paresh , Majeti Ravindra , Wei Andrew H. , Garcia-Manero Guillermo , Craddock Charles , Sallman David A. , Kantarjian Hagop M. 
Published: October 2022

Abstract

TP53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) form a distinct group of myeloid disorders with dismal outcomes. TP53-mutated MDS and AML have lower response rates to either induction chemotherapy, hypomethylating agent–based regimens, or venetoclax-based therapies compared with non–TP53-mutated counterparts and a poor median overall survival of 5 to 10 months. Recent advances have identified novel pathogenic mechanisms in TP53-mutated myeloid malignancies, which have the potential to improve treatment strategies in this distinct clinical subgroup. In this review, we discuss recent insights into the biology of TP53-mutated MDS/AML, current treatments, and emerging therapies, including immunotherapeutic and nonimmune-based approaches for this entity.

Significance:
Emerging data on the impact of cytogenetic aberrations, TP53 allelic burden, immunobiology, and tumor microenvironment of TP53-mutated MDS and AML are further unraveling the complexity of this disease. An improved understanding of the functional consequences of TP53 mutations and immune dysregulation in TP53-mutated AML/MDS coupled with dismal outcomes has resulted in a shift from the use of cytotoxic and hypomethylating agent–based therapies to novel immune and nonimmune strategies for the treatment of this entity. It is hoped that these novel, rationally designed combinations will improve outcomes in this area of significant unmet need.
Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell–like Program Conserved in HPV-Positive Cancers
Authors: Leiendecker Lukas , Neumann Tobias , Jung Pauline S. , Cronin Shona M. , Steinacker Thomas L. , Schleiffer Alexander , Schutzbier Michael , Mechtler Karl , Kervarrec Thibault , Laurent Estelle , Bachiri Kamel , Coyaud Etienne , Murali Rajmohan , Busam Klaus J. , Itzinger-Monshi Babak , Kirnbauer Reinhard , Cerroni Lorenzo , Calonje Eduardo , Rütten Arno , Stubenrauch Frank , Griewank Klaus G. , Wiesner Thomas , Obenauf Anna C. 
Published: October 2022

Abstract

The skin is exposed to viral pathogens, but whether they contribute to the oncogenesis of skin cancers has not been systematically explored. Here we investigated 19 skin tumor types by analyzing off-target reads from commonly available next-generation sequencing data for viral pathogens. We identified human papillomavirus 42 (HPV42) in 96% (n = 45/47) of digital papillary adenocarcinoma (DPA), an aggressive cancer occurring on the fingers and toes. We show that HPV42, so far considered a nononcogenic, “low-risk” HPV, recapitulates the molecular hallmarks of oncogenic, “high-risk” HPVs. Using machine learning, we find that HPV-driven transformation elicits a germ cell–like transcriptional program conserved throughout all HPV-driven cancers (DPA, cervical carcinoma, and head and neck cancer). We further show that this germ cell–like transcriptional program, even when reduced to the top two genes (CDKN2A and SYCP2), serves as a fingerprint of oncogenic HPVs with implications for early detection, diagnosis, and therapy of all HPV-driven cancers.

Significance:
We identify HPV42 as a uniform driver of DPA and add a new member to the short list of tumorigenic viruses in humans. We discover that all oncogenic HPVs evoke a germ cell–like transcriptional program with important implications for detecting, diagnosing, and treating all HPV-driven cancers.
See related commentary by Starrett et al., p. 17.
This article is highlighted in the In This Issue feature, p. 1
Hippo Signaling Pathway Regulates Cancer Cell–Intrinsic MHC-II Expression
Authors: Zeng Zexian , Gu Shengqing Stan , Ouardaoui Nofal , Tymm Carly , Yang Lin , Wong Cheryl J. , Li Dian , Zhang Wubing , Wang Xiaoqing , Weirather Jason L. , Rodig Scott J. , Hodi F. Stephen , Brown Myles , Liu X. Shirley 
Published: October 2022

Abstract

MHC-II is known to be mainly expressed on the surface of antigen-presenting cells. Evidence suggests MHC-II is also expressed by cancer cells and may be associated with better immunotherapy responses. However, the role and regulation of MHC-II in cancer cells remain unclear. In this study, we leveraged data mining and experimental validation to elucidate the regulation of MHC-II in cancer cells and its role in modulating the response to immunotherapy. We collated an extensive collection of omics data to examine cancer cell–intrinsic MHC-II expression and its association with immunotherapy outcomes. We then tested the functional relevance of cancer cell–intrinsic MHC-II expression using a syngeneic transplantation model. Finally, we performed data mining to identify pathways potentially involved in the regulation of MHC-II expression, and experimentally validated candidate regulators. Analyses of preimmunotherapy clinical samples in the CheckMate 064 trial revealed that cancer cell–intrinsic MHC-II protein was positively correlated with more favorable immunotherapy outcomes. Comprehensive meta-analyses of multiomics data from an exhaustive collection of data revealed that MHC-II is heterogeneously expressed in various solid tumors, and its expression is particularly high in melanoma. Using a syngeneic transplantation model, we further established that melanoma cells with high MHC-II responded better to anti–PD-1 treatment. Data mining followed by experimental validation revealed the Hippo signaling pathway as a potential regulator of melanoma MHC-II expression. In summary, we identified the Hippo signaling pathway as a novel regulator of cancer cell–intrinsic MHC-II expression. These findings suggest modulation of MHC-II in melanoma could potentially improve immunotherapy response.
Resolved Gravity Waves in the Extratropical Stratosphere: Effect of Horizontal Resolution Increase from O(10) to O(1) km
Authors: Polichtchouk Inna , van Niekerk Annelize , Wedi Nils 
Published: October 2022

Abstract
Global ECMWF IFS simulations with horizontal grid spacings of 1, 4, and 9 km are used to assess gravity wave forcing (GWF) in the extratropical stratosphere. Results with important implications for GWF parameterizations at high and intermediate resolutions are presented. A doubling in the zonal-mean resolved GWF is observed when the horizontal resolution is increased from 9 to 1 km. Small-scale gravity waves with horizontal wavelengths < 100 km dominate this increase. Over most regions, excluding the polar night jet in the Antarctic spring, the total (resolved + parameterized) GWF at 9 km (4 km) is underestimated by up to 30% (15%). This implies that the parameterization of GWF is still required at 9 and 4 km horizontal resolutions. Despite the small land area in the Southern Hemisphere (SH), the resolved orographic and nonorographic GWF contribute equally to the total GWF in the SH at 1 km resolution. This is not reflected in the partitioning of the parameterized GWF, which has a significantly larger nonorographic contribution at 9 km. As a result, a zonal-mean momentum budget analysis reveals that the total GWF contributes one-third of SH springtime polar vortex deceleration at 1 km, whereas the contribution is as much as 50% at 9 km. This suggests that a rebalancing of the parameterized nonorographic and orographic GWF is required.
Anchoring Intraseasonal Air–Sea Interactions: The Moored Moist Static Energy Budget in the Indian Ocean from Reanalysis
Authors: Rydbeck Adam V. , A. Christophersen Jonathan , Flatau Maria K. , Janiga Matthew A. , Jensen Tommy G. , Reynolds Carolyn A. , Ridout James A. , Smith Travis A. , Wijesekera Hemantha 
Published: October 2022

Abstract
Moist static energy (MSE) and ocean heat content (OHC) in the tropics are inextricably linked. The processes by which sources and sinks of OHC modulate column integrated MSE in the Indian Ocean (IO) are explored through a reformulation of the MSE budget using atmosphere and ocean reanalysis data. In the reframed MSE budget, interfacial air–sea turbulent and radiative fluxes are replaced for information on upper ocean dynamics, thus “mooring” the MSE tendency to the subsurface ocean. On subseasonal time scales, ocean forcing is largely responsible for the amplification of MSE anomalies across the IO, with basin average growth rates of 10% day−1. Local OHC depletion is the leading contributor to anomalous MSE amplification with average rates of 12% day−1. Along the equator, MSE is amplified by OHC vertical advection. Ocean forcing only weakly reduces the propagation tendency of MSE anomalies (−2% day−1), with propagation predominantly resulting from atmosphere forcing (10% day−1). OHC in the IO acts as an MSE reservoir that is expended during periods of enhanced intraseasonal atmosphere convection and recharged during periods of suppressed convection. Because OHC is an MSE source during enhanced intraseasonal convection periods, it largely offsets the negative MSE tendency produced by horizontal advection in the atmosphere. The opposite effect occurs during suppressed convection periods, where OHC is a sink of MSE and counters the positive MSE tendency produced by horizontal advection in the atmosphere.