bluuebunny/crossref_metadata_2025 huggingface dataset:
Foreclosure spillovers and individual well‐being: Evidence from the Great Recession
Authors: Makridis Christos A. , Ohlrogge Michael
Published: July 2021

This paper explores the causal effect of foreclosure on individual well‐being. Using plausibly exogenous variation in the timing of interest rate changes on different types of adjustable rate mortgages, we find that a 10% rise in foreclosures is associated with a 0.58% and 0.28% decline in current and expected future life satisfaction. These effects are primarily driven by the effects on local economic optimism. The results are consistent with models of spatial externalities where large‐scale shocks generate adverse effects on communities, not just individuals.
Aqueous extract prepared from steamed red amaranth (Amaranthus gangeticus L.) leaves protected human lens cells against high glucose induced glycative and oxidative stress
Authors: Hsiao Li‐Wei , Tsay Gregory J. , Mong Mei‐Chin , Liu Wen‐Hu , Yin Mei‐Chin
Published: July 2021

HLE‐B3 cell line, a human lens epithelial cell line, was used to examine the anti‐glycative and anti‐oxidative protection of aqueous extract prepared from steamed red amaranth leaves against high glucose induced injury. Phytochemical profile of this aqueous extract was analyzed. HLE‐B3 cells were pretreated by this aqueous extract at 0.25%, 0.5%, or 1%, and followed by high glucose treatment. Results showed that the content of phenolic acids, flavonoids, anthocyanins, carotenoids, and triterpenoids in this aqueous extract was in the range of 1,107–2,861 mg/100 g dry weight. High glucose decreased cells viability and suppressed Bcl‐2 mRNA expression. This aqueous extract pretreatments raised 11–42% cell survival and upregulated 20–47% Bcl‐2 mRNA expression. High glucose reduced Na+‐K+ ATPase activity and mitochondrial membrane potential (MMP). This aqueous extract raised 27–40% Na+‐K+ ATPase activity, and 18–51% MMP. High glucose stimulated the generation of total advanced glycative endproducts (AGEs), methylglyoxal, and reactive oxygen species (ROS). This aqueous extract pretreatments lowered total AGEs, methylglyoxal, and ROS levels in the range of 0.38–1.17 folds, 1.7–4.9 nmol/mg protein, and 0.35–1.06 relative fluorescence unit/mg protein. High glucose upregulated mRNA expression of aldose reductase, nuclear factor kappa B, and p38. This aqueous extract pretreatments decreased mRNA expression of these factors in the range of 75–159%, 57–151%, and 54–166%. High glucose downregulated mRNA expression of nuclear factor E2‐related factor 2 (Nrf2). This aqueous extract pretreatments increased 12–38% Nrf2 mRNA expression. These results suggested that this aqueous extract might be a potent nutritional supplement to prevent diabetic retinopathy.
The fermentation‐time dependent proteolysis profile and peptidomic analysis of fermented soybean curd
Authors: Wei Guanmian , Regenstein Joe M , Zhou Peng
Published: July 2021

The proteolysis and peptidomic profiles and potential bioactivities of fermented soybean curd (furu) during fermentation were studied. The degree of protein hydrolysis (DH) and peptide content significantly increased with fermentation time (p < 0.05), and reached the highest levels after ripening for 90 days. The variety and abundance of bioactive peptides in furu samples were fermentation‐time dependent, and furu ripening for 30 and 90 days showed the highest similarity. An ACE‐inhibitor and antioxidant peptides were the two main bioactive peptide components, and their abundance and bioactivities exhibited a significant increase with fermentation and reached the maximum levels at 90 days. All these results indicated that microbial fermentation is an effective way to obtain bioactive peptides with soy‐based fermented products, and their effects on health might be explored in future studies.

Practical Application

This work indicated that microbial fermentation is an effective way to obtain bioactive peptides with soy‐based fermented products.
pr2‐primers: An 18S rRNA primer database for protists
Authors: Vaulot Daniel , Geisen Stefan , Mahé Frédéric , Bass David
Published: July 2021

Metabarcoding of microbial eukaryotes (collectively known as protists) has developed tremendously in the last decade, almost solely relying on the 18S rRNA gene. As microbial eukaryotes are extremely diverse, many primers and primer pairs have been developed. To cover a relevant and representative fraction of the protist community in a given study system, an informed primer choice is necessary, as no primer pair can target all protists equally well. As such, a smart primer choice is very difficult even for experts and there are very few online resources available to list existing primers. We built a database listing 285 primers and 83 unique primer pairs that have been used for eukaryotic 18S rRNA gene metabarcoding. In silico performance of primer pairs was tested against two sequence databases: PR2 version 4.12.0 for eukaryotes and a subset of silva version 132 for bacteria and archaea. We developed an R‐based web application enabling browsing of the database, visualization of the taxonomic distribution of the amplified sequences with the number of mismatches, and testing any user‐defined primer or primer set (https://app.pr2‐primers.org). Taxonomic specificity of primer pairs, amplicon size and location of mismatches can also be determined. We identified universal primer sets that matched the largest number of sequences and analysed the specificity of some primer sets designed to target certain groups. This tool enables guided primer choices that will help a wide range of researchers to include protists as part of their investigations.
Performance of myositis‐specific antibodies detected on myositis line immunoassay to diagnose and sub‐classify patients with suspected idiopathic inflammatory myopathy, a retrospective records‐based review
Authors: Beaton Thomas J. , Gillis David , Prain Kerri , Morwood Karen , Anderson James , Goddard John , Baird Timothy
Published: July 2021

Aim

To evaluate myositis line immunoassay (LIA) for diagnosis and sub‐classification of suspected idiopathic inflammatory myopathy (IIM). To investigate if test performance is improved by increasing signal strength cut‐off for myositis‐specific antibody (MSA) or combining MSA with indirect immunofluorescence (IIF).

Methods

A retrospective, consecutive case series of patients investigated for MSAs from June 2013 to June 2020 for suspected IIM. Specificity, sensitivity, positive predictive value, and negative predictive value were calculated with 95% confidence intervals for diagnosis of IIM. Association of IIM diagnosis with increased signal strength and presence of an expected IIF pattern on Hep‐2 cells was assessed by Fisher’s exact test in MSA‐positive patients.

Results

A total of 195 patients were evaluated. IIM was diagnosed in 32/195 (16.4%) patients. MSAs were detected in 41/195 (21%) patients, 18/41 (43.9%) patients with an MSA had a diagnosis of IIM. The probability of an IIM diagnosis was increased in MSA‐positive patients with high compared with low signal strength (83.3% vs 43.5%; P = 0.01) and an expected compared with unexpected IIF pattern (61.5% vs 23.8%; P = 0.04). Specificity for IIM was not significantly improved by increasing signal strength cut‐off (85.9% vs 93.8%). Positive predictive value of myositis LIA was only modest and not significantly improved by either increasing signal strength cut‐off or requiring an expected IIF pattern for determination of MSA positivity (43.9% vs 60% vs 61.5%). Sub‐classification of IIM correlated closely for respective MSAs (88.9%).

Conclusion

Increased MSA signal strength on myositis LIA and the presence of an expected IIF pattern were associated with IIM diagnosis. Test performance was non‐significantly improved by these methods. Prevalence of IIM in this patient cohort was low; it is not excluded that LIA performance could be improved by these methods in a higher prevalence cohort.
Fatal outcome and intensive care unit admission after total hip and knee arthroplasty: An analytic of preoperative frailty and comorbidities
Authors: Laursen Christina C. , Meyhoff Christian S. , Petersen Tonny S. , Jimenez‐Solem Espen , Sørensen Anne M. S. , Lunn Troels H.
Published: July 2021

Background

With increasing demand for total hip arthroplasty (THA) and total knee arthroplasty (TKA), a higher percentage of patients are identified with comorbidities that might increase the risk of complications. We aimed to elucidate the preoperative characteristics of patients with a fatal outcome or admission to the Intensive Care Unit (ICU) within 90 days after THA or TKA. We arbitrarily hypothesized that more than 50% of those patients would be frail.

Methods

This is a register based, explorative study including patients undergoing elective, unilateral, primary THA or TKA in the Capital Region of Denmark from 2010 to 2017, and who subsequently died or were admitted to the ICU within 90 days. The modified Frailty Index (mFI) was calculated from the medical records, and a score of ≥0.36 defined frailty.

Results

A total of 33,758 patients underwent THA or TKA, and 284 patients (0.8%) died or were admitted to the ICU within 90 days. Fifty‐seven patients (20%) were frail (95% CI 16.2–25.7%). The most common comorbidities were hypertension (63%) and pulmonary diseases (32%), and 56% used walking aids. Two or more comorbidities were present in 65% of patients, and 14% had no comorbidities at all.

Conclusion

Only 20% of patients with a fatal outcome or ICU admission after elective THA or TKA could be categorized as frail based on the mFI. Further studies with a prospective design are needed to clarify the mFI as a risk stratification tool in elderly multimorbid patients undergoing elective arthroplasty surgery.
Jail and overdose: assessing the community impact of incarceration on overdose
Authors: Victor Grant , Zettner Catherine , Huynh Philip , Ray Bradley , Sightes Emily
Published: July 2021

Background and aims

Incarceration produces a specific public health threat for drug overdose, and correctional settings do not offer medication for opioid use disorder. This study examined the overall impact of jail incarceration on overdose, the specific hazard for those booked on a syringe‐related charge and the proportion of all overdose decedents in the community who were in the jail prior to death.

Design and setting

A cohort study of fatal overdose outcomes among a sample of individuals booked into and released from jail between 1 January 2017 and 31 December 2019. Marion County, IN, USA.

Participants

All individuals released from one county jail between 1 January 2017 and 31 December 2017 and decedents who died within the county from an accidental fatal overdose between January 2017 and December 2019.

Measurements and findings

Using information on all jail booking events, including charge type, during a 5‐year period (January 2015–December 2019), we looked at the hazard of accidental fatal overdose post‐release, controlling for age, sex and race. Of all overdose deaths in the county, 21% (n = 237) had been in the county jail within 2 years prior to their death. Each prior booking increased the hazard of mortality by approximately 20% [hazard ratio (HR) = 1.21, 95% confidence interval (CI) = 1.15, 1.28], while the presence of a syringe charge at most recent booking prior to release more than tripled the hazard of mortality (HR = 3.55, 95% CI = 2.55, 4.93).

Conclusions

In Marion County, IN, USA, there appears to be an association between increased risk of fatal drug overdose and both syringe‐related arrests and repeat jail bookings.
Scripting the Conviction: Power and Resistance in the Management of Criminal Stigma
Authors: Burch Melissa
Published: July 2021

People with criminal records seeking employment face a dilemma: how to discuss their conviction(s) in a job interview. Convicted job seekers are encouraged to draft, revise, and rehearse their “conviction scripts” and to approach their delivery as a Goffmanian performance. Drawing from participant observation within a nonprofit employment program in Southern California, this article analyzes job seekers’ attempts to craft narratives that will satisfy employers’ curiosities and concerns, with the assistance of professional coaches. I find that rather than challenge criminalizing practices or stigma itself, job seekers are encouraged to dissociate from criminal stigma and develop narratives that reinforce dominant frameworks of personal responsibility, remorse, and rehabilitation. They also regularly veer, however, from these conventions, in search of narratives that more accurately explain and contextualize their decisions. I argue that the act of scripting convictions is thus a political process in motion, a negotiation of power, with real life consequences. While at present, conviction scripting tends to reproduce the inequalities that underlie the criminal punishment system, the article concludes by exploring how criminalized people could craft scripts that contribute to their liberation. [stigma, criminalization, race, criminal records, employment]
Higher FT4 level within the normal range predicts the outcome of cryoballoon ablation in paroxysmal atrial fibrillation patients without structural heart disease
Authors: Pei Yan , Xu Shaojie , Yang Haotian , Ren Zhongyuan , Meng Weilun , Zheng Yixing , Guo Rong , Li Shuang , Zhao Dongdong , Tang Kai , Li Hailing , Xu Yawei
Published: July 2021

Background

Accumulated evidence has indicated that a high‐normal FT4 level is an independent risk factor for the clinical progression of AF. However, the association between elevated FT4 concentration within the normal range and AF recurrence after cryoballoon ablation in China is unknown.

Methods

This retrospective and observational study included 453 AF patients who underwent cryoballoon ablation from January 2016 to August 2018. Patients were classified into quartiles based on preprocedural serum FT4 concentration. The clinical characteristics of the patients and the long‐term rate of AF recurrence after ablation were assessed.

Results

After a mean follow‐up period of 17.4 ± 9.0 months, 91 (20.1%) patients suffered from AF recurrence. The AF recurrence rate by FT4 quartile was 17.7%, 19.0%, 21.4%, and 22.3% for participants with FT4 in quartile 1, 2, 3, and 4, respectively (p < .001). On multivariate Cox regression, FT4 concentration (HR: 1.187, 95% CI: 1.093–1.290, p < .001) and left atrial diameter (HR: 1.052, 95% CI: 1.014–1.092, p = .007) were significant predictors of AF recurrence. When stratifying for AF type, the rate of postoperative recurrence was independently increased as FT4 concentration increased in paroxysmal AF, but not in persistent AF (p < .001 in paroxysmal AF and p = .977 in persistent AF).

Conclusion

Higher FT4 level within the normal range predicted the outcome of cryoballoon ablation in Chinese paroxysmal AF patients without structural heart disease.
Safety of electrooxidation for urea removal in a wearable artificial kidney is compromised by formation of glucose degradation products
Authors: van Gelder Maaike K. , Vollenbroek Jeroen C. , Lentferink Babette H. , Hazenbrink Diënty H. M. , Besseling Paul J. , Simonis Frank , Giovanella Silvia , Ligabue Giulia , Bajo Rubio Maria A. , Cappelli Gianni , Joles Jaap A. , Verhaar Marianne C. , Gerritsen Karin G. F.
Published: July 2021

A major challenge for the development of a wearable artificial kidney (WAK) is the removal of urea from the spent dialysate, as urea is the waste solute with the highest daily molar production and is difficult to adsorb. Here we present results on glucose degradation products (GDPs) formed during electrooxidation (EO), a technique that applies a current to the dialysate to convert urea into nitrogen, carbon dioxide, and hydrogen gas. Uremic plasma and peritoneal effluent were dialyzed for 8 hours with a WAK with and without EO‐based dialysate regeneration. Samples were taken regularly during treatment. GDPs (glyoxal, methylglyoxal, and 3‐deoxyglucosone) were measured in EO‐ and non‐EO‐treated fluids. Glyoxal and methylglyoxal concentrations increased 26‐ and 11‐fold, respectively, in uremic plasma (at [glucose] 7 mmol/L) and 209‐ and 353‐fold, respectively, in peritoneal effluent (at [glucose] 100 mmol/L) during treatment with EO, whereas no change was observed in GDP concentrations during dialysate regeneration without EO. EO for dialysate regeneration in a WAK is currently not safe due to the generation of GDPs which are not biocompatible.
No association between chronic use of ranitidine, compared with omeprazole or famotidine, and gastrointestinal malignancies
Authors: Kim Yeseong D. , Wang Jiasheng , Shibli Fahmi , Poels Kamrine E. , Ganocy Stephen J. , Fass Ronnie
Published: July 2021

Background

In 2019, the United States Food and Drug Administration detected above‐regulation levels of the human carcinogen N‐nitrosodimethylamine (NDMA) in ranitidine, resulting in a complete removal of the medication from the market. NDMA is known to cause gastrointestinal malignancies in animal models.

Aim

To determine if patients who were receiving ranitidine have a higher risk of developing cancers of the digestive tract compared to patients taking other anti‐reflux medications.

Methods

Using the nationwide database IBM Explorys, patients taking ranitidine were compared to patients on either famotidine or omeprazole. Incidence data of new malignancies of the oesophagus, stomach, liver, pancreas, and colon/rectum were obtained in 1‐year intervals for up to 10 years. Two multivariable logistic regression models were used to calculate odds ratios (ORs), one adjusting for common risk factors for each cancer studied, and the other for demographic factors.

Results

Patients on ranitidine who were compared to patients on famotidine had ORs of 0.51(95% CI 0.43‐0.60), 0.43(95% CI 0.36‐0.51), 0.39(95% CI 0.36‐0.41), 0.54(95% CI 0.49‐0.62), and 0.46(95% CI 0.43‐0.49) of developing oesophageal, gastric, hepatocellular, pancreatic, and colorectal cancers, respectively (P < 0.001). Patients on ranitidine compared to omeprazole had ORs of 0.62(95% CI 0.52‐0.72), 0.58(95% CI 0.49‐0.68), 0.81 (95% CI 0.76‐0.86), 0.68(95% CI 0.60‐0.76), and 0.66(95% CI 0.62‐0.70) of developing oesophageal, gastric, hepatocellular, pancreatic, and colorectal cancers respectively (P < 0.001).

Conclusions

Use of ranitidine was not associated with an increased odds of developing gastrointestinal malignancies compared to omeprazole or famotidine use.
Exposure to night‐time light pollution and risk of prolonged duration of labor: A nationwide cohort study
Authors: Windsperger Karin , Kiss Herbert , Oberaigner Wilhelm , Leitner Hermann , Binder Franz , Muin Dana A. , Foessleitner Philipp , Husslein Peter W. , Farr Alex
Published: July 2021

Background

Light pollution (LP) is a ubiquitous environmental agent that affects more than 80% of the world's population. This large nationwide cohort study evaluates whether exposure to LP can influence obstetric outcomes.

Methods

We analyzed Austrian birth registry data on 717 113 cases between 2008 and 2016 and excluded cases involving day‐time delivery, <23 + 0 gestational weeks, and/or birthweight <500 g, induction of labor, elective cesarean, or cases with missing data. The independent variable, that is, degree of night‐time LP, was categorized as low (0.174 to <0.688 mcd/m2), medium (0.688 to <3 mcd/m2), or high (3 to <10 mcd/m2). Duration of labor and adverse neonatal outcomes served as outcome measures.

Results

Cases in regions with high LP (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.30‐1.57) and medium LP (OR, 1.22; 95% CI, 1.14‐1.31) showed increased odds of prolonged labor (P < .0001 each). Newborns born in regions with high LP (OR, 1.12; 95% CI, 1.07‐1.16) and medium LP (OR, 1.07; 95% CI, 1.04‐1.10) showed increased odds of experiencing adverse outcomes (P < .0001 each). Preterm delivery <28 + 0 weeks was also associated with the degree of LP (P = .04).

Conclusions

Night‐time LP negatively interferes with obstetric outcomes. The perceived influence of LP as an environmental agent needs to be re‐evaluated to minimize associated health risks.
Leukemogenesis via aberrant self‐renewal by the MLL/AEP‐mediated transcriptional activation system
Authors: Yokoyama Akihiko
Published: July 2021

Homeostasis of the hematopoietic system is achieved in a hierarchy, with hematopoietic stem cells at the pinnacle. Because only hematopoietic stem cells (HSCs) can self‐renew, the size of the hematopoietic system is strictly controlled. In hematopoietic reconstitution experiments, 1 HSC can reconstitute the entire hematopoietic system, whereas 50 multipotent progenitors cannot. This indicates that only HSCs self‐renew, whereas non‐HSC hematopoietic progenitors are programmed to differentiate or senesce. Oncogenic mutations of the mixed lineage leukemia gene (MLL) overcome this “programmed differentiation” by conferring the self‐renewing ability to non‐HSC hematopoietic progenitors. In leukemia, mutated MLL proteins constitutively activate a broad range of previously transcribed CpG‐rich promoters by an MLL‐mediated transcriptional activation system. This system promotes self‐renewal by replicating an expression profile similar to that of the mother cell in its daughter cells. In this transcriptional activation system, MLL binds to unmethylated CpG‐rich promoters and recruits RNA polymerase II. MLL recruits p300/CBP through its transcriptional activation domain, which acetylates histone H3 at lysines 9, 18, and 27. The AF4 family/ENL family/P‐TEFb complex (AEP) binds to acetylated H3K9/18/27 to activate transcription. Gene rearrangements of MLL with AEP‐ or CBP/p300‐complex components generate constitutively active transcriptional machinery of this transcriptional activation system, which causes aberrant self‐renewal of leukemia stem cells. Inhibitors of the components of this system effectively decrease their leukemogenic potential.
Role of BCLAF‐1 in PD‐L1 stabilization in response to ionizing irradiation
Authors: Ma Zhao , Wang Han , Meng Fanbiao , Han Yamei , Chen Yefei , Xiao Mingming , Jiang Hongjing , Yu Zhentao , Xu Bo
Published: July 2021

Programmed cell death ligand 1 (PD‐L1) is a major immunosuppressive checkpoint protein expressed by tumor cells to subvert anticancer immunity. Recent studies have shown that ionizing radiation (IR) upregulates the expression of PD‐L1 in tumor cells. However, whether an IR‐induced DNA damage response (DDR) directly regulates PD‐L1 expression and the functional significance of its upregulation are not fully understood. Here, we show that IR‐induced upregulation of PD‐L1 expression proceeds through both transcriptional and post‐translational mechanisms. Upregulated PD‐L1 was predominantly present on the cell membrane, resulting in T‐cell apoptosis in a co‐culture system. Using mass spectrometry, we identified PD‐L1 interacting proteins and found that BCLAF1 (Bcl2 associated transcription factor 1) is an important regulator of PD‐L1 in response to IR. BCLAF1 depletion decreased PD‐L1 expression by promoting the ubiquitination of PD‐L1. In addition, we show that CMTM6 is upregulated in response to IR and participates in BCLAF1‐dependent PD‐L1 upregulation. Finally, we demonstrated that the ATM/BCLAF1/PD‐L1 axis regulated PD‐L1 stabilization in response to IR. Together, our findings reveal a novel regulatory mechanism of PD‐L1 expression in the DDR.
Pyroptosis, a new bridge to tumor immunity
Authors: Li Lisha , Jiang Mingxia , Qi Ling , Wu Yiming , Song Dongfeng , Gan Junqing , Li Yanjing , Bai Yuxian
Published: July 2021

Pyroptosis refers to the process of gasdermin (GSDM)‐mediated programmed cell death (PCD). Our understanding of pyroptosis has expanded beyond cells and is known to involve extracellular responses. Recently, there has been an increasing interest in pyroptosis due to its emerging role in activating the immune system. In the meantime, pyroptosis‐mediated therapies, which use the immune response to kill cancer cells, have also achieved notable success in a clinical setting. In this review, we discuss that the immune response induced by pyroptosis activation is a double‐edged sword that affects all stages of tumorigenesis. On the one hand, the activation of inflammasome‐mediated pyroptosis and the release of pyroptosis‐produced cytokines alter the immune microenvironment and promote the development of tumors by evading immune surveillance. On the other hand, pyroptosis‐produced cytokines can also collect immune cells and ignite the immune system to improve the efficiency of tumor immunotherapies. Pyroptosis is also related to some immune checkpoints, especially programmed death‐1 (PD‐1) or programmed death‐ ligand 1 (PD‐L1). In this review, we mainly focus on our current understanding of the interplay between the immune system and tumors that process through pyroptosis, and debate their use as potential therapeutic targets.
Novel immune‐related signature for risk stratification and prognosis in prostatic adenocarcinoma
Authors: Zhao Hai‐Bo , Zeng Yan‐Ru , Han Zhao‐Dong , Zhuo Yang‐Jia , Liang Ying‐Ke , Hon Chi Tin , Wan Song , Wu Shulin , Dahl Douglas , Zhong Wei‐De , Wu Chin‐Lee
Published: July 2021

A substantial proportion of prostatic adenocarcinoma (PRAD) patients experience biochemical failure (BCF) after radical prostatectomy (RP). The immune microenvironment plays a vital role in carcinogenesis and the development of PRAD. This study aimed to identify a novel immune‐related gene (IRG)‐based signature for risk stratification and prognosis of BCF in PRAD. Weighted gene coexpression network analysis was carried out to identify a BCF‐related module in a discovery cohort of patients who underwent RP at the Massachusetts General Hospital. The median follow‐up time was 70.32 months. Random forest and multivariate stepwise Cox regression analyses were used to identify an IRG‐based signature from the specific module. Risk plot analyses, Kaplan‐Meier curves, receiver operating characteristic curves, univariate and multivariate Cox regression analyses, stratified analysis, and Harrell’s concordance index were used to assess the prognostic value and predictive accuracy of the IRG‐based signature in the internal discovery cohort; The Cancer Genome Atlas database was used as a validation cohort. Tumor immune estimation resource database analysis and CIBERSORT algorithm were used to assess the immunophenotype of PRAD. A novel IRG‐based signature was identified from the specific module. Five IRGs (BUB1B, NDN, NID1, COL4A6, and FLRT2) were verified as components of the risk signature. The IRG‐based signature showed good prognostic value and predictive accuracy in both the discovery and validation cohorts. Infiltrations of various immune cells were significantly different between low‐risk and high‐risk groups in PRAD. We identified a novel IRG‐based signature that could function as an index for assessing tumor immune status and risk stratification in PRAD.
Pre‐schoolers use head gestures rather than prosodic cues to highlight important information in speech
Authors: Esteve‐Gibert Núria , Lœvenbruck Hélène , Dohen Marion , D'Imperio Mariapaola
Published: July 2021

Previous evidence suggests that children's mastery of prosodic modulations to signal the informational status of discourse referents emerges quite late in development. In the present study, we investigate the children's use of head gestures as it compares to prosodic cues to signal a referent as being contrastive relative to a set of possible alternatives. A group of French‐speaking pre‐schoolers were audio‐visually recorded while playing in a semi‐spontaneous but controlled production task, to elicit target words in the context of broad focus, contrastive focus, or corrective focus utterances. We analysed the acoustic features of the target words (syllable duration and word‐level pitch range), as well as the head gesture features accompanying these target words (head gesture type, alignment patterns with speech). We found that children's production of head gestures, but not their use of either syllable duration or word‐level pitch range, was affected by focus condition. Children mostly aligned head gestures with relevant speech units, especially when the target word was in phrase‐final position. Moreover, the presence of a head gesture was linked to greater syllable duration patterns in all focus conditions. Our results show that (a) 4‐ and 5‐year‐old French‐speaking children use head gestures rather than prosodic cues to mark the informational status of discourse referents, (b) the use of head gestures may gradually entrain the production of adult‐like prosodic features, and that (c) head gestures with no referential relation with speech may serve a linguistic structuring function in communication, at least during language development.
Insulin strategies for dietary fat and protein in type 1 diabetes: A systematic review
Authors: Smith Tenele A. , Marlow Alexandra A. , King Bruce R. , Smart Carmel E.
Published: July 2021

Aim

To identify and report the efficacy of insulin strategies used to manage glycaemia following fat and/or fat and protein meals in type 1 diabetes.

Methods

A systematic literature search of medical databases from 1995 to 2021 was undertaken. Inclusion criteria were randomised controlled trials that reported at least one of the following glycaemic outcomes: mean glucose, area under the curve, time in range or hypoglycaemic episodes.

Results

Eighteen studies were included. Thirteen studies gave additional insulin. Five studies gave an additional 30%–43% of the insulin‐to‐carbohydrate ratio (ICR) for 32–50 g of fat and 31%–51% ICR for 7–35 g of fat with 12–27 g of protein added to control meals. A further eight studies gave −28% to +75% ICR using algorithms based on fat and protein for meals with 19–50 g of carbohydrate, 2–79 g of fat and 10–60 g of protein, only one study reported a glycaemic benefit of giving less than an additional 24% ICR. Eight studies evaluated insulin delivery patterns. Four of six studies in pump therapy, and one of two studies in multiple daily injections showed the combination of bolus and split dose, respectively, were superior. Five studies examined the insulin dose split, four demonstrated 60%–125% ICR upfront was necessary. Two studies investigated the timing of insulin delivery, both reported administration 15 min before the meal lowered postprandial glycaemia.

Conclusions

Findings highlight the glycaemic benefit of an additional 24%–75% ICR for fat and fat and protein meals. For these meals, there is supportive evidence for insulin delivery in a combination bolus with a minimum upfront dose of 60% ICR, 15 min before the meal.
100 years of physiology, discrimination and wonder
Authors: Russell‐Jones David , Herring Roselle
Published: July 2021

There has been 100 years of research detailing the role of insulin in glucose, protein and free fatty acid metabolism. We explore the learnings though evolution and changes in management with an understanding of how it has impacted the care of people with diabetes. The discrimination endured is described and recent advances to empower and counter this are highlighted.
Sexual health and function in women with diabetes
Authors: Winkley Kirsty , Kristensen Camilla , Fosbury Jackie
Published: July 2021

Sexual dysfunction for women with diabetes is more common than for women without diabetes. The reasons why women with diabetes are a high‐risk group are numerous. For example, lack of vaginal lubrication, pain during sex and inability to orgasm can be a consequence of high or low blood glucose levels. Higher rates of depression in people with diabetes can lead to low sexual drive. Wearing of diabetes devices, such as pumps, glucose monitors or lumps from lipohypertrophy around insulin injection sites may affect body image and self‐esteem and the inconvenience of self‐managing diabetes may affect the spontaneity of sex. This narrative review provides an overview of the problem of sexual dysfunction in women with diabetes, current methods of assessing sexual dysfunction in women, pharmacological and non‐pharmacological interventions to treat it and an example of how psychological support for women with diabetes who experience sexual dysfunction can be integrated into a diabetes service. There are still significant gaps in our knowledge of how best to support women with diabetes and sexual dysfunction. However, raising awareness of the problem may help women with diabetes and healthcare professionals to discuss it as part of diabetes clinical consultations.
Product heterogeneity in international terms of payment
Authors: Im Hyejoon
Published: July 2021

This study examines the effects of product characteristics on the choice of payment methods for international trade. I develop a theoretical model that leads to two new testable hypotheses. First, as the transaction value increases, exporters tend to choose safer payment methods, such as letters of credit, rather than post‐shipment payments. Second, if the products in the transaction are easily liquidated, exporters tend to choose safer payment terms. Product‐destination‐level export data from Korean exports declaration forms support both hypotheses. Furthermore, the results using these comprehensive data on tradable goods and countries generalize the findings of previous studies on country characteristics.
Protocols for inducing homeostatic plasticity reflected in the corticospinal excitability in healthy human participants: A systematic review and meta‐analysis
Authors: Wittkopf Priscilla G. , Larsen Dennis B. , Graven‐Nielsen Thomas
Published: July 2021

Homeostatic plasticity complements synaptic plasticity by stabilising neural activity within a physiological range. In humans, homeostatic plasticity is investigated using two blocks of non‐invasive brain stimulation (NIBS) with an interval without stimulation between blocks. The aim of this systematic review and meta‐analysis was to investigate the effect of homeostatic plasticity induction protocols on motor evoked potentials (MEP) in healthy participants. Four databases were searched (Medline, Scopus, Embase and Cochrane library). Studies describing the application of two blocks of NIBS of the primary motor cortex with an interval of no stimulation between blocks reporting changes in corticospinal excitability by MEP amplitude were included. Thirty‐seven reports with 55 experiments (700 participants) were included. Study quality was considered poor overall, with heterogeneity in study size, sample and designs. Two blocks of excitatory stimulation at the primary motor cortex produced a homeostatic response (decreased MEP) between 0 and 30 min post‐protocols, when compared with a single stimulation block. Two blocks of inhibitory stimulation at the primary motor cortex using interval duration of 10 min or less produced a homeostatic response (increased MEP) between 0 and 30 min post‐protocols, when compared with a single stimulation block. There were no differences in MEPs when compared with baseline MEPs. In conclusion, homeostatic plasticity induction using two blocks of NIBS with an interval of 10 min or less without stimulation between blocks produces a homeostatic response up to 30 min post‐protocol. Improvements in participant selection, sample sizes and protocols of NIBS techniques are needed.
Local delivery of fingolimod through PLGA nanoparticles and PuraMatrix‐embedded neural precursor cells promote motor function recovery and tissue repair in spinal cord injury
Authors: Zeraatpisheh Zahra , Mirzaei Esmaeil , Nami Mohammad , Alipour Hamed , Mahdavipour Marzieh , Sarkoohi Parisa , Torabi Somayyeh , Azari Hassan , Aligholi Hadi
Published: July 2021

Spinal cord injury (SCI) is a devastating clinical problem that can lead to permanent motor dysfunction. Fingolimod (FTY720) is a sphingosine structural analogue, and recently, its therapeutic benefits in SCI have been reported. The present study aimed to evaluate the therapeutic efficacy of fingolimod‐incorporated poly lactic‐co‐glycolic acid (PLGA) nanoparticles (nanofingolimod) delivered locally together with neural stem/progenitor cells (NS/PCs) transplantation in a mouse model of contusive acute SCI. Fingolimod was encapsulated in PLGA nanoparticles by the emulsion–evaporation method. Mouse NS/PCs were harvested and cultured from embryonic Day 14 (E14) ganglionic eminences. Induction of SCI was followed by the intrathecal delivery of nanofingolimod with and without intralesional transplantation of PuraMatrix‐encapsulated NS/PCs. Functional recovery, injury size and the fate of the transplanted cells were evaluated after 28 days. The nanofingolimod particles represented spherical morphology. The entrapment efficiency determined by UV–visible spectroscopy was approximately 90%, and the drug content of fingolimod loaded nanoparticles was 13%. About 68% of encapsulated fingolimod was slowly released within 10 days. Local delivery of nanofingolimod in combination with NS/PCs transplantation led to a stronger improvement in neurological functions and minimized tissue damage. Furthermore, co‐administration of nanofingolimod and NS/PCs not only increased the survival of transplanted cells but also promoted their fate towards more oligodendrocytic phenotype. Our data suggest that local release of nanofingolimod in combination with three‐dimensional (3D) transplantation of NS/PCs in the acute phase of SCI could be a promising approach to restore the damaged tissues and improve neurological functions.
Immune checkpoint inhibitors for progressive multifocal leukoencephalopathy: Identifying relevant outcome factors
Authors: Lambert Nicolas , El Moussaoui Majdouline , Maquet Pierre
Published: July 2021

Introduction

Progressive multifocal leukoencephalopathy (PML) is an infectious brain disease caused by JC virus in immunocompromised individuals. Immune checkpoint inhibitors (ICIs) recently emerged as a therapeutic hope for these patients but identification of those likely to respond to the treatment is still an unmet need.

Method

We performed a systematic PubMed search for reports of patients treated for PML using an ICI. Clinical, biological and radiological characteristics were contrasted between patients who responded to the treatment (RP) and those who did not (NRP).

Results

Thirty‐five patients were included in the present study. Twenty‐one of them reportedly benefited from the treatment. Age, blood CD4+ cells count, pretreatment viral load in the cerebrospinal fluid (CSF), PML lesions localization, treatment delay since first PML symptoms, type of ICI used and immune‐related adverse events (irAEs) occurrence did not significantly differ between RP and NRP. By contrast, a history of therapeutic immune suppression and the use of an immunosuppressive therapy at treatment initiation were significantly associated with a poor response. Besides, reaching an undetectable viral load in the CSF and reduction of the lesion load on magnetic resonance imaging after ICI administration was associated with a good clinical response.

Conclusion

Current data suggest that patients with PML under immunosuppressive therapy are less likely to respond to ICIs and raises the issue of the optimal management of irAEs during ICI treatment in this setting.
Factors associated with long‐term outcomes in pediatric refractory status epilepticus
Authors: Gaínza‐Lein Marina , Barcia Aguilar Cristina , Piantino Juan , Chapman Kevin E. , Sánchez Fernández Iván , Amengual‐Gual Marta , Anderson Anne , Appavu Brian , Arya Ravindra , Brenton James Nicholas , Carpenter Jessica L. , Clark Justice , Farias‐Moeller Raquel , Gaillard William D. , Glauser Tracy A. , Goldstein Joshua L. , Goodkin Howard P. , Huh Linda , Kahoud Robert , Kapur Kush , Lai Yi‐Chen , McDonough Tiffani L. , Mikati Mohamad A. , Morgan Lindsey A. , Nayak Anuranjita , Novotny Edward , Ostendorf Adam P. , Payne Eric T. , Peariso Katrina , Reece Latania , Riviello James , Sannagowdara Kumar , Sands Tristan T. , Sheehan Theodore , Tasker Robert C. , Tchapyjnikov Dmitry , Vasquez Alejandra , Wainwright Mark S. , Wilfong Angus , Williams Korwyn , Zhang Bo , Loddenkemper Tobias ,   the Pediatric Status Epilepticus Research Group
Published: July 2021

Objective

This study was undertaken to describe long‐term clinical and developmental outcomes in pediatric refractory status epilepticus (RSE) and identify factors associated with new neurological deficits after RSE.

Methods

We performed retrospective analyses of prospectively collected observational data from June 2011 to March 2020 on pediatric patients with RSE. We analyzed clinical outcomes from at least 30 days after RSE and, in a subanalysis, we assessed developmental outcomes and evaluated risk factors in previously normally developed patients.

Results

Follow‐up data on outcomes were available in 276 patients (56.5% males). The median (interquartile range [IQR]) follow‐up duration was 1.6 (.9–2.7) years. The in‐hospital mortality rate was 4% (16/403 patients), and 15 (5.4%) patients had died after hospital discharge. One hundred sixty‐six (62.9%) patients had subsequent unprovoked seizures, and 44 (16.9%) patients had a repeated RSE episode. Among 116 patients with normal development before RSE, 42 of 107 (39.3%) patients with available data had new neurological deficits (cognitive, behavioral, or motor). Patients with new deficits had longer median (IQR) electroclinical RSE duration than patients without new deficits (10.3 [2.1–134.5] h vs. 4 [1.6–16] h, p = .011, adjusted odds ratio = 1.003, 95% confidence interval = 1.0008–1.0069, p = .027). The proportion of patients with an unfavorable functional outcome (Glasgow Outcome Scale‐Extended score ≥ 4) was 22 of 90 (24.4%), and they were more likely to have received a continuous infusion.

Significance

About one third of patients without prior epilepsy developed recurrent unprovoked seizures after the RSE episode. In previously normally developing patients, 39% presented with new deficits during follow‐up, with longer electroclinical RSE duration as a predictor.
Vesicular hand eczema transcriptome analysis provides insights into its pathophysiology
Authors: Voorberg Angelique N. , Niehues Hanna , Oosterhaven Jart A. F. , Romeijn Geertruida L. E. , van Vlijmen‐Willems Ivonne M. J. J. , van Erp Piet E. J. , Ederveen Thomas H. A. , Zeeuwen Patrick L. J. M. , Schuttelaar Marie L. A.
Published: July 2021

Hand eczema is a common inflammatory skin condition of the hands whose pathogenesis is largely unknown. More insight and knowledge of the disease on a more fundamental level might lead to a better understanding of the biological processes involved, which could provide possible new treatment strategies. We aimed to profile the transcriptome of lesional palmar epidermal skin of patients suffering from vesicular hand eczema using RNA‐sequencing. RNA‐sequencing was performed to identify differentially expressed genes in lesional vs. non‐lesional palmar epidermal skin from a group of patients with vesicular hand eczema compared to healthy controls. Comprehensive real‐time quantitative PCR analyses and immunohistochemistry were used for validation of candidate genes and protein profiles for vesicular hand eczema. Overall, a significant and high expression of genes/proteins involved in keratinocyte host defense and inflammation was found in lesional skin. Furthermore, we detected several molecules, both up or downregulated in lesional skin, which are involved in epidermal differentiation. Immune signalling genes were found to be upregulated in lesional skin, albeit with relatively low expression levels. Non‐lesional patient skin showed no significant differences compared to healthy control skin. Lesional vesicular hand eczema skin shows a distinct expression profile compared to non‐lesional skin and healthy control skin. Notably, the overall results indicate a large overlap between vesicular hand eczema and earlier reported atopic dermatitis lesional transcriptome profiles, which suggests that treatments for atopic dermatitis could also be effective in (vesicular) hand eczema.
Fermatean fuzzy set extensions of SAW, ARAS, and VIKOR with applications in COVID‐19 testing laboratory selection problem
Authors: Gül Sait
Published: July 2021

The multiple attribute decision‐making models are empowered with the support of fuzzy sets such as intuitionistic, q‐rung orthopair, Pythagorean, and picture fuzzy sets, and also neutrosophic sets, etc. These concepts generate varying representation opportunities for the decision‐maker's preferences and expertise. Pythagorean and Fermatean fuzzy sets are special cases of q‐rung orthopair fuzzy set when q = 2 and q = 3, respectively. From a geometric perspective, the latter provides a broader representation domain than the former does. In this study, the emerging concept of Fermatean fuzzy set is studied in detail and three well‐known multi‐attribute evaluation methods, namely SAW, ARAS, and VIKOR are extended under Fermatean fuzzy environment. In this manner, the decision‐makers will have more freedom in specifying their preferences, thoughts, and expertise, and the abovementioned decision approaches will be able to handle this new type of data. The applicability of the propositions is shown in determining the best Covid‐19 testing laboratory which is an important topic of the ongoing global health crisis. To validate the proposed methods, a benchmark analysis covering the results of the existing Fermatean fuzzy set‐based decision methods, namely TOPSIS, WPM, and Yager aggregation operators is presented.
Trajectories of relationship and individual functioning among waitlisted couples for an online relationship intervention
Authors: Barton Allen W. , Lavner Justin A. , Hawrilenko Matthew J. , Doss Brian D.
Published: July 2021

To inform research and practice with distressed couples, the current study was designed to examine patterns of change among distressed, help‐seeking couples prior to receiving an intervention. Data from this study originate from 221 couples assigned to the waitlist control condition of a randomized controlled trial for couples seeking online help for their relationship. All couples self‐selected into the online program and agreed to withhold seeking additional services for their relationship during the waitlist period. In contrast with prior findings, results from the current study indicated a general pattern of mean improvement in both self‐reported relationship functioning (e.g., increased relationship satisfaction, partner emotional support) and self‐reported individual functioning (i.e., decreased psychological distress, anger) over the six‐month waitlist period. Nonetheless, the majority of couples continued to remain relationally distressed despite these improvements. Findings from the study indicate that distressed couples can, in fact, exhibit some degree of improvement absent of intervention. At the same time, overall levels of distress remained elevated, indicating that these improvements are not sufficient to result in high levels of functioning and suggesting that many distressed couples may benefit from empirically supported programs to realize greater gains. These results also highlight and underscore the importance of including control conditions in studies examining the efficacy of relationship interventions with distressed couples to ensure that any observed improvements in relationship functioning are attributable to the intervention rather than to naturally occurring changes.