bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subjective Changes of Taste and Smell in Conjunction With Anxiety and Depression Are Associated With Symptoms in Globus Patients Without Evidence of Pathologic Acid Reflux
Authors: Liu Jie , Wang Wei , Wang Ying , Wu Dewei , Sun Chenyu , Lv Chaolan , Wu Dandan , Yu Yue 
Published: August 2021

Background/Aim:
Patients suffering from globus often report decreased enjoyment when eating as well as a psychological abnormality. Some patients exhibit taste and smell changes (TSCs) when compared with the period before the diagnosis. The main aim of this study was to explore if TSCs and psychological abnormality are present in patients with globus, whether they are associated with the severity of throat symptoms, and the potential risk factors for globus.

Patients and Methods:
A total of 116 included patients who met the Rome IV diagnostic criteria for globus had been performed 24-hour pH monitoring, and the results shown no evidence of pathologic acid reflux. Meanwhile, 125 healthy controls were enrolled in this prospective study. All subjects completed several questionnaires including the Taste and Smell Survey, the Glasgow Edinburgh Throat Scale, the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD). Multiple logistic regression was performed to explore the potential risk factors for globus. The study protocol was registered on the Chinese Clinical Trial Registry (No. ChiCTR-2100044972).

Results:
First, globus patients without evidence of pathologic acid reflux exhibited a 58.62% and 31.03% change in taste and smell, respectively, while their levels of anxiety and depression were 51.72% and 44.83%, respectively. Second, there was a significant difference in the taste score (Z=−4.954, P<0.001) and smell score (Z=−4.552, P<0.001) between globus group patients and healthy controls. Similarly, globus group patients had a higher HAMA score (9.52±2.437 vs. 3.12±1.059, t=6.867, P<0.001) and HAMD score (9.79±2.931 vs. 3.16±1.650, t=6.416, P<0.001) when compared with the healthy controls. Third, in globus group patients, the Glasgow Edinburgh Throat Scale was significantly correlated with the taste score (Spearman ρ=0.782; P<0.001), smell score (Spearman ρ=0.582; P=0.001), HAMA (Spearman ρ=0.676; P<0.001), and HAMD (Spearman ρ=0.672; P<0.001). In addition, the taste score was significantly correlated with HAMA (Spearman ρ=0.532; P=0.004) and HAMD (Spearman ρ=0.681; P<0.001), while the smell score was significantly correlated with HAMD (Spearman ρ=0.392; P=0.035). Finally, multivariate logistic regression revealed that TSCs, anxiety, and depression were significant independent risk factors for globus, with depression exhibiting the highest degree of association (odds ratio: 3.244).

Conclusions:
TSCs and psychological comorbidities are prominent in globus patients without evidence of pathologic acid reflux. The obtained results indicated that there is a strong relationship between TSCs, psychological comorbidities, and globus. Therefore, awareness of this high prevalence of TSCs and psychological disorder may help to better understand the severity of throat symptoms.
The Effect of Acupressure on Relieving Cancer-Related Fatigue
Authors: Hsieh Shu-Hua , Wu Chia-Rung , Romadlon Debby Syahru , Hasan Faizul , Chen Pin-Yuan , Chiu Hsiao-Yean 
Published: August 2021

Background
Fatigue, a common complaint reported by patients with cancer or in survivorship, has been negatively associated with quality of life, emotional health, and cognitive functions. Acupressure, a traditional Chinese medicine, has been increasingly practiced in clinical and community settings. However, little evidence supports the beneficial effects of acupressure on the reduction of general, physical, and mental fatigue in cancer survivors.

Objective
The aim of this study was to examine the effect of acupressure on fatigue in cancer survivors and the moderators of the effect of acupressure on cancer-related fatigue relief.

Methods
Databases, namely, PubMed, Embase, CINAHL, and ProQuest, were searched from their inception to July 17, 2020. No language and publication period restrictions were applied. Only randomized controlled trials that examined the effects of acupressure on cancer-related fatigue were included. A random-effects model was used for data analyses.

Results
Fourteen articles involving 776 participants with cancers were included. Acupressure considerably alleviated cancer-related general, physical, and mental fatigue (g = −0.87, −0.87, and −0.37) compared with controls. Increasing female percentage of participants significantly reduced the effects of acupressure on fatigue (B = −0.01, P < .001). The executor and operation approach as well as treatment period during chemotherapy did not moderate the effects of acupressure on fatigue relief.

Conclusion
Acupressure is effective at alleviating cancer-related fatigue.

Implications for Practice
Health professionals and patients can use acupressure to alleviate fatigue during and after chemotherapy. Nursing personnel could incorporate acupressure into clinical practice as part of a multimodal approach to alleviating fatigue in cancer survivors.
Possible Bioenergetic Biomarker for Chronic Cancer-Related Fatigue
Authors: Hsiao Chao-Pin , Daly Barbara , Chen Mei-Kuang , Veigl Marty , Dorth Jennifer , Ponsky Lee Evan , Hoppel Charles 
Published: August 2021

Background
Cancer-related fatigue (CRF) is a highly prevalent, debilitating, and persistent symptom experienced by patients receiving cancer treatments. Up to 71% of men with prostate cancer receiving radiation therapy experience acute and persistent CRF. There is neither an effective therapy nor a diagnostic biomarker for CRF. This pilot study aimed to discover potential biomarkers associated with chronic CRF in men with prostate cancer receiving radiation therapy.

Methods
We used a longitudinal repeated-measures research design. Twenty men with prostate cancer undergoing radiation therapy completed all study visits. CRF was evaluated by a well-established and validated questionnaire, the Patient-Reported Outcomes Measurement Information System for Fatigue (PROMIS-F) Short Form. In addition, peripheral blood mononuclear cells were harvested to quantify ribonucleic acid (RNA) gene expression of mitochondria-related genes. Data were collected before, during, on completion, and 24 months postradiation therapy and analyzed using paired t-tests and repeated-measures analysis of variance.

Results
The mean of the PROMIS-F T score was significantly increased over time in patients with prostate cancer, remaining elevated at 24 months postradiation therapy compared to baseline. A significant downregulated BC1 ubiquinol-cytochrome c reductase synthesis-like (BCS1L) was observed over time during radiation therapy and at 24 months postradiation therapy. An increased PROMIS-F score was trended with downregulated BCS1L in patients 24 months after completing radiation therapy.

Discussion
This is the first evidence to describe altered messenger RNA for BCS1L in chronic CRF using the PROMIS-F measure with men receiving radiation therapy for prostate cancer.

Conclusion
Our results suggest that peripheral blood mononuclear cell messenger RNA for BCS1L is a potential biomarker and therapeutic target for radiation therapy-induced chronic CRF in this clinical population.
Be Prepared
Authors: Kishida Mizue , Daly Guris Rodrigo J. , Monachino AnneMarie , Hales Roberta , Benson Danielle C. , Good Grace , Hamburger Marjorie A. , Widmeier Keith , Dove Aleeshamonae , Ades Anne M. , Nadkarni Vinay M. , Nishisaki Akira 
Published: August 2021

Introduction
The COVID-19 pandemic forced healthcare institutions to rapidly adapt practices for patient care, staff safety, and resource management. We evaluated contributions of the simulation center in a freestanding children's hospital during the early stages of the pandemic.

Methods
We reviewed our simulation center's activity for education-based and system-focused simulation for 2 consecutive academic years (AY19: 2018–2019 and AY20: 2019–2020). We used statistical control charts and χ2 analyses to assess the impact of the pandemic on simulation activity as well as outputs of system-focused simulation during the first wave of the pandemic (March–June 2020) using the system failure mode taxonomy and required level of resolution.

Results
A total of 1983 event counts were reported. Total counts were similar between years (994 in AY19 and 989 in AY20). System-focused simulation was more prevalent in AY20 compared with AY19 (8% vs. 2% of total simulation activity, P < 0.001), mainly driven by COVID-19–related simulation events. COVID-19–related simulation occurred across the institution, identified system failure modes in all categories except culture, and was more likely to identify macro-level issues than non–COVID-19–related simulation (64% vs. 44%, P = 0.027).

Conclusions
Our simulation center pivoted to deliver substantial system-focused simulation across the hospital during the first wave of the COVID-19 pandemic. Our experience suggests that simulation centers are essential resources in achieving safe and effective hospital-wide improvement.
Drug repurposing of metformin for Alzheimer’s disease: Combining causal inference in medical records data and systems pharmacology for biomarker identification
Authors: Charpignon Marie-Laure , Vakulenko-Lagun Bella , Zheng Bang , Magdamo Colin , Su Bowen , Evans Kyle , Rodriguez Steve , Sokolov Artem , Boswell Sarah , Sheu Yi-Han , Somai Melek , Middleton Lefkos , Hyman Bradley T. , Betensky Rebecca A. , Finkelstein Stan N. , Welsch Roy E. , Tzoulaki Ioanna , Blacker Deborah , Das Sudeshna , Albers Mark W. 
Published: August 2021

ABSTRACTMetformin, an antidiabetic drug, triggers anti-aging cellular responses. Aging is the principal risk factor for dementia, but previous observational studies of the diabetes drugs metformin vs. sulfonylureas have been mixed. We tested the hypotheses that metformin improves survival and reduces the risk of dementia, relative to the sulfonylureas, by emulating target trials in electronic health records of diabetic patients at an academic-centered healthcare system in the US and a wide-ranging group of primary care practices in the UK. To address metformin’s potentially dual influences on dementia risk—that it might reduce the hazard of death and put more people at risk of developing dementia while reducing the hazard of dementia by slowing biological aging, we used a competing risks approach and carefully grounded that within a causal inference emulated trial framework. To identify candidate biomarkers of metformin’s actions in the brain that might mediate reduced dementia risk, we conducted an in-vitro systems pharmacology evaluation of metformin and glyburide on differentiated human neural cells through differential gene expression. We named our multi-dimensional approach DRIAD-EHR (Drug Repurposing in Alzheimer’s Disease-Electronic Health Records). In intention-to-treat analyses, metformin was associated with a lower hazard of all-cause mortality than sulfonylureas in both cohorts. In competing risks analyses, there was also a lower cause-specific hazard of dementia onset among metformin initiators. In in-vitro studies, metformin reduced human neural cell expression ofSPP1andAPOE, two secreted proteins that have been implicated in Alzheimer’s disease pathogenesis and whose levels can be quantified in the CSF. Together, our findings suggest that metformin might prevent dementia in patientswithouttype II diabetes. In addition, our results inform the design of clinical trials of metformin in non-diabetics and suggest a pharmacodynamic CSF biomarker, SPP1, for metformin’s action in the brain.
Pleural fluid analysis in neutropenia
Authors: Budnick Isadore M. , Oliver Samuel F. , Barros Andrew J. , Sturek Jeffrey M. 
Published: August 2021

ABSTRACTLight’s criteria is the standard for determining the etiology of pleural effusions. Test characteristics of Light’s criteria varies in different populations, and Light’s criteria may misclassify effusions in patients with impaired immunity such as in neutropenia. This study evaluates the test characteristics of Light’s criteria and other clinically available pleural fluid tests in a cohort of patients with neutropenia. Cases were defined as a thoracentesis performed with an absolute neutrophil count of less than 1000 cells/µl documented at least 24 hours prior to the procedure. The etiology of the effusion was adjudicated by independent review of the case data and hospital course by two board certified pulmonologists. Categories for final diagnosis included exudate due to infection, exudate due to malignancy, exudate due to other, and transudate. A total of 83 thoracenteses from 80 patients were identified. Comorbidities included hematologic and solid tumor malignancies, recipients of allogeneic stem cell and solid organ transplants, heart failure, chronic kidney disease, and decompensated cirrhosis. Light’s criteria had a sensitivity of 92% and a specificity of 55% for identifying exudates, LR+ 2.07 and LR-0.14. A pleural fluid protein value of >2.9 g/dl had a sensitivity of 42% and a specificity of 96%, LR+11.12 and LR-0.61. When comparing exudative effusions, the percentage of neutrophils in the pleural fluid was significantly higher in infection, despite peripheral neutropenia. Together these results show a reduced specificity of Light’s criteria in neutropenia, and underscore the complexity of pleural effusions in this setting.
Geospatial Variability in Excess Death Rates during the COVID-19 Pandemic in Mexico: Examining Socio Demographic and Population Health Characteristics
Authors: Dahal Sushma , Luo Ruiyan , Swahn Monica H. , Chowell Gerardo 
Published: August 2021

AbstractBackgroundMexico has suffered one of the highest COVID-19 mortality rates in the world. In this study we examined how socio demographic and population health characteristics shape the geospatial variability in excess mortality patterns during the COVID-19 pandemic in Mexico.MethodsWeekly all-cause mortality time series for all 32 Mexican states, from January 4, 2015 to April 10, 2021, were analyzed to estimate the excess mortality rates using Serfling regression models. The association between socio-demographic, health indicators and excess mortality rates were determined using multiple linear regression analyses. Finally, we used functional data analysis to characterize clusters of states with distinct mortality growth rate curves.ResultsThe overall all-cause excess deaths rate during the COVID-19 pandemic in Mexico until April 10, 2021 was estimated at 39.66 per 10 000 population. The lowest excess death rates were observed in southeastern states including Chiapas (12.72), Oaxaca (13.42) and Quintana Roo (19.41) whereas Mexico City had the highest excess death rate (106.17), followed by Tlaxcala (51.99) and Morelos (45.90). We found a positive association of excess mortality rates with aging index (P value<.0001), marginalization index (P value<.0001), and average household size (P value=0.0003) in the final adjusted model (Model R2=76%). We identified four distinct clusters with qualitatively similar excess mortality curves.ConclusionCentral states exhibited the highest excess mortality rates whereas the distribution of aging index, marginalization index, and average household size explained the variability in excess mortality rates across Mexico. Our findings can help tailor interventions to mitigate the mortality impact of the pandemic.Key messageThis study quantified and examined spatial patterns of excess mortality across states of Mexico, with lower rates of excess mortality in southeastern states and higher rates in central states.Mexico City recorded 1 in 5 of all excess deaths in reported in Mexico, which accounted for 19% of total excess deaths across the country.Findinds indicate that aging index, marginalization index, and average household size played a significant role on excess death rates across Mexican states during the COVID-19 pandemic.Four distinct clusters characterized the excess mortality curves across Mexican states.
Open reading frame correction using antisense oligonucleotides for the treatment of cystic fibrosis caused by CFTR-W1282X
Authors: Michaels Wren E. , Pena-Rasgado Cecilia , Kotaria Rusudan , Bridges Robert J. , Hastings Michelle L. 
Published: August 2021

AbstractCFTRgene mutations that result in the introduction of premature termination codons (PTCs) are common in cystic fibrosis (CF). This mutation type causes a severe form of the disease, likely because of lowCFTRmRNA expression as a result of nonsense mediated mRNA decay (NMD), as well as production of a non-functional, truncated CFTR protein. Current therapeutics for CF, which target residual protein function, are less effective in patients with these types of mutations, due in part to low CFTR protein levels. Splice-switching antisense oligonucleotides (ASOs) designed to induce skipping of exons in order to restore the mRNA open reading frame have shown therapeutic promise pre-clinically and clinically for a number of diseases. We hypothesized that ASO-mediated skipping of CFTR exon 23 would recover CFTR activity associated with terminating mutations in the exon, includingCFTRp.W1282X, the 5thmost common mutation in CF. Here, we show that CFTR lacking the amino acids encoding exon 23 is partially functional and responsive to corrector and modulator drugs currently in clinical use. ASO-induced exon 23 skipping rescued CFTR expression and chloride current in primary human bronchial epithelial cells isolated from homozygote CFTR-W1282X patients. These results support the use of ASOs in treating CF patients withCFTRclass I mutations in exon 23 that result in unstableCFTRmRNA and truncations of the CFTR protein.Significance StatementFrameshift and nonsense mutations pose a major problem for disease therapeutic development. Eliminating these mutations from the mRNA by inducing exon skipping is a relatively unexplored treatment approach, though it has shown promise for some diseases. Here, we show that eliminating a common stop mutation associated with cystic fibrosis by inducing skipping of the exon it is located in, results in a restoration of the open reading frame and recovers CFTR protein function in a manner expected to be therapeutic in CF patients who don’t currently have effective treatment options. These results are an important advancement for the cystic fibrosis community but also have implications for other diseases where terminating mutations are responsible for dysfunction.
Structural Differences In 3C-like protease (Mpro) From SARS-CoV and SARS-CoV-2: Molecular Insights For Drug Repurposing Against COVID-19 Revealed by Molecular Dynamics Simulations
Authors: Parmar Meet , Thumar Ritik , Patel Bhumi , Athar Mohd , Jha Prakash C. , Patel Dhaval 
Published: August 2021

AbstractA recent fatal outbreak of novel coronavirus SARS-CoV-2, identified preliminary as a causative agent for series of unusual pneumonia cases in Wuhan city, China has infected more than 20 million individuals with more than 4 million mortalities. Since, the infection crossed geographical barriers, the WHO permanently named the causing disease as COVID-2019 by declaring it a pandemic situation. SARS-CoV-2 is an enveloped single-stranded RNA virus causing a wide range of pathological conditions from common cold symptoms to pneumonia and fatal severe respiratory syndrome. Genome sequencing of SARS-CoV-2 has revealed 96% identity to the bat coronavirus and 79.6% sequence identity to the previous SARS-CoV. The main protease (known as 3C-like proteinase/ Mpro) plays a vital role during the infection with the processing of replicase polyprotein thus offering an attractive target for therapeutic interventions. SARS-CoV and SARS-CoV-2 Mpro shares 97% sequence identity, with 12 variable residues but none of them present in the catalytic and substrate binding site. With the high level of sequence and structural similarity and absence of any drug/vaccine against SARS-CoV-2, drug repurposing against Mpro is an effective strategy to combat COVID-19. Here, we report a detailed comparison of SARS-CoV-2 Mpro with SARS-CoV Mpro using molecular dynamics simulations to assess the impact of 12 divergent residues on the molecular microenvironment of Mpro. A structural comparison and analysis is made on how these variable residues affects the intra-molecular interactions between key residues in the monomer and biologically active dimer form of Mpro. The present MD simulations study concluded the change in microenvironment of active-site residues at the entrance (T25, T26, M49 and Q189), near the catalytic region (F140, H163, H164, M165 and H172) and other residues in substrate binding site (V35T, N65S, K88R and N180K) due to 12 mutation incorporated in the SARS-CoV-2 Mpro. It is also evident that SARS-CoV-2 dimer is more stable and less flexible state compared to monomer which may be due to these variable residues, mainly F140, E166 and H172 which are involved in dimerization. This also warrants a need for inhibitor design considering the more stable dimer form. The mutation accumulated in SARS-CoV-2 Mpro indirectly reconfigures the key molecular networks around the active site conferring a potential change in SARS-CoV-2, thus posing a challenge in drug repurposing SARS drugs for COVID-19. The new networks and changes in microenvironment identified by our work might guide attempts needed for repurposing and identification of new Mpro inhibitors.
Organization and dynamics of the cortical complexes controlling insulin secretion in β-cells
Authors: Noordstra Ivar , van den Berg Cyntha M. , Boot Fransje W. J. , Katrukha Eugene A. , Yu Ka Lou , Tas Roderick P. , Portegies Sybren , Viergever Bastiaan J. , de Graaff Esther , Hoogenraad Casper C. , de Koning Eelco J. P. , Carlotti Françoise , Kapitein Lukas C. , Akhmanova Anna 
Published: August 2021

AbstractInsulin secretion in pancreatic β-cells is regulated by cortical complexes that are enriched at the sites of adhesion to extracellular matrix facing the vasculature. Many components of these complexes, including Bassoon, RIM, ELKS and liprins, are shared with neuronal synapses. Here, we show that insulin secretion sites also contain non-neuronal proteins LL5β and KANK1, which in migrating cells organize exocytotic machinery in the vicinity of integrin-based adhesions. Depletion of LL5β or focal adhesion disassembly triggered by myosin II inhibition perturbed the clustering of secretory complexes and attenuated the first wave of insulin release. While previous analyses in vitro and in neurons suggested that secretory machinery might assemble through liquid-liquid phase separation, analysis of endogenously labeled ELKS in pancreatic islets indicated that its dynamics is inconsistent with such a scenario. Instead, fluorescence recovery after photobleaching and single molecule imaging showed that ELKS turnover is driven by binding and unbinding to low-mobility scaffolds. Both the scaffold movements and ELKS exchange were stimulated by glucose treatment. Our findings help to explain how integrin-based adhesions control spatial organization of glucose-stimulated insulin release.