bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structures of nonsense-mediated mRNA decay factors UPF3B and UPF3A in complex with UPF2 reveal molecular basis for competitive binding and for neurodevelopmental disorder-causing mutation
Authors: Bufton Joshua C , Powers Kyle T , Szeto Jenn-Yeu A , Toelzer Christine , Berger Imre , Schaffitzel Christiane 
Published: May 2022

Abstract
UPF3 is a key nonsense-mediated mRNA decay (NMD) factor required for mRNA surveillance and eukaryotic gene expression regulation. UPF3 exists as two paralogs (A and B) which are differentially expressed depending on cell type and developmental stage and believed to regulate NMD activity based on cellular requirements. UPF3B mutations cause intellectual disability. The underlying molecular mechanisms remain elusive, as many of the mutations lie in the poorly characterized middle-domain of UPF3B. Here, we show that UPF3A and UPF3B share structural and functional homology to paraspeckle proteins comprising an RNA-recognition motif-like domain (RRM-L), a NONA/paraspeckle-like domain (NOPS-L), and extended α-helical domain. These domains are essential for RNA/ribosome-binding, RNA-induced oligomerization and UPF2 interaction. Structures of UPF2′s third middle-domain of eukaryotic initiation factor 4G (MIF4GIII) in complex with either UPF3B or UPF3A reveal unexpectedly intimate binding interfaces. UPF3B’s disease-causing mutation Y160D in the NOPS-L domain displaces Y160 from a hydrophobic cleft in UPF2 reducing the binding affinity ∼40-fold compared to wildtype. UPF3A, which is upregulated in patients with the UPF3B-Y160D mutation, binds UPF2 with ∼10-fold higher affinity than UPF3B reliant mainly on NOPS-L residues. Our characterization of RNA- and UPF2-binding by UPF3′s middle-domain elucidates its essential role in NMD.
PCGA: a comprehensive web server for phenotype-cell-gene association analysis
Authors: Xue Chao , Jiang Lin , Zhou Miao , Long Qihan , Chen Ying , Li Xiangyi , Peng Wenjie , Yang Qi , Li Miaoxin 
Published: May 2022

Abstract
Most complex disease-associated loci mapped by genome-wide association studies (GWAS) are located in non-coding regions. It remains elusive which genes the associated loci regulate and in which tissues/cell types the regulation occurs. Here, we present PCGA (https://pmglab.top/pcga), a comprehensive web server for jointly estimating both associated tissues/cell types and susceptibility genes for complex phenotypes by GWAS summary statistics. The web server is built on our published method, DESE, which represents an effective method to mutually estimate driver tissues and genes by integrating GWAS summary statistics and transcriptome data. By collecting and processing extensive bulk and single-cell RNA sequencing datasets, PCGA has included expression profiles of 54 human tissues, 2,214 human cell types and 4,384 mouse cell types, which provide the basis for estimating associated tissues/cell types and genes for complex phenotypes. We develop a framework to sequentially estimate associated tissues and cell types of a complex phenotype according to their hierarchical relationships we curated. Meanwhile, we construct a phenotype-cell-gene association landscape by estimating the associated tissues/cell types and genes of 1,871 public GWASs. The association landscape is generally consistent with biological knowledge and can be searched and browsed at the PCGA website.
Cytosolic microRNA-inducible nuclear translocation of Cas9 protein for disease-specific genome modification
Authors: Shin Cheol-Hee , Park Su Chan , Park Il-Geun , Kim Hyerim , An Byoungha , Lee Choongil , Kim Sang-Heon , Lee Juyong , Lee Ji Min , Oh Seung Ja 
Published: May 2022

Abstract
MicroRNA-dependent mRNA decay plays an important role in gene silencing by facilitating posttranscriptional and translational repression. Inspired by this intrinsic nature of microRNA-mediated mRNA cleavage, here, we describe a microRNA-targeting mRNA as a switch platform called mRNA bridge mimetics to regulate the translocation of proteins. We applied the mRNA bridge mimetics platform to Cas9 protein to confer it the ability to translocate into the nucleus via cleavage of the nuclear export signal. This system performed programmed gene editing in vitro and in vivo. Combinatorial treatment with cisplatin and miR-21-EZH2 axis-targeting CRISPR Self Check-In improved sensitivity to chemotherapeutic drugs in vivo. Using the endogenous microRNA-mediated mRNA decay mechanism, our platform is able to remodel a cell's natural biology to allow the entry of precise drugs into the nucleus, devoid of non-specific translocation. The mRNA bridge mimetics strategy is promising for applications in which the reaction must be controlled via intracellular stimuli and modulates Cas9 proteins to ensure safe genome modification in diseased conditions.
Allosteric regulation of noncoding RNA function by microRNAs
Authors: Gorbea Carlos , Elhakiem Abdalla , Cazalla Demián 
Published: May 2022

Abstract
HSUR1 and HSUR2, two noncoding RNAs expressed by the oncogenic Herpesvirus saimiri, bind host microRNAs miR-142-3p, miR-16, and miR-27 with different purposes. While binding of miR-27 to HSUR1 triggers the degradation of the microRNA, miR-16 is tethered by HSUR2 to target host mRNAs to repress their expression. Here we show that the interaction with miR-142-3p is required for the activity of both HSURs. Coimmunoprecipitation experiments revealed that miR-142-3p allosterically regulates the binding of miR-27 and miR-16 to HSUR1 and HSUR2, respectively. The binding of two different miRNAs to each HSUR is not cooperative. HSURs can be engineered to be regulated by other miRNAs, indicating that the identity of the binding miRNA is not important for HSUR regulation. Our results uncover a mechanism for allosteric regulation of noncoding RNA function and a previously unappreciated way in which microRNAs can regulate gene expression.
Adrenal insufficiency is common amongst kidney transplant recipients receiving maintenance prednisolone and can be predicted using morning cortisol
Authors: Tomkins Maria , Martin-Grace Julie , Kennedy Carmel , McEnroe Olive , Heverin Karen , Srinivasan Shari , Little Dilly , Conlon Peter , De Freitas Declan , Denton Mark , Magee Colm , O'Seaghdha Conall , O'Reilly Michael W , Thompson Chris J , Sherlock Mark 
Published: May 2022

ABSTRACT

Background
Long-term glucocorticoid therapy is a key component of immunosuppression for kidney transplant recipients (KTRs), leading to significant cumulative glucocorticoid exposure. The aims of this study are to investigate the prevalence of adrenal insufficiency (AI) in KTRs taking prednisolone and to develop a screening algorithm to identify patients at the highest risk of AI.

Methods
In this cross-sectional cohort study, 67 KTRs receiving prednisolone underwent a short synacthen test (SST) and measurement of cumulative glucocorticoid exposure.

Results
A total of 72% (n = 48) of participants failed the SST. Participants with AI had a higher daily prednisolone dose (4.9 versus 4.2 mg/day; P = .002) and greater cumulative glucocorticoid exposure (289 versus 111 mg/kg; P = .03) than those with intact adrenal function. Participants with AI had lower baseline cortisol than participants with intact adrenal function (143 versus 303 nmol/L; P &lt; .001). Morning cortisol of &gt;288 nmol/L predicted a normal SST with 100% specificity [95% confidence interval (CI) 92–100] and 70% sensitivity (95% CI 56–78%), therefore excluding AI.

Conclusions
Our results suggest KTRs are at a higher risk for AI than previously reported. A morning serum cortisol measurement is a useful screening tool in this cohort, reducing the need for stimulatory testing by 44%. KTRs with AI need education regarding glucocorticoid sick rules, similar to patients with other forms of AI.
End-proximal tubule phosphate concentration increases as GFR falls in humans: measurement by means of a lithium clearance-based methodology
Authors: Colussi Giacomo , Menegotto Alberto , Querques Marialuisa , Ravera Federica , Verdesca Simona , Colombo Valeriana , Minetti Enrico E 
Published: May 2022

ABSTRACTBackgroundMicroscopic nephrocalcinosis secondary to intratubular calcium phosphate (CaP) precipitation is thought to accelerate progression to end-stage renal failure in chronic kidney diseases. In phosphorus (P)-loaded uninephrectomized rats, intratubular CaP crystal formation and progressive tubular damage occurred when end-proximal tubule P concentration (ePTpc) increased above a threshold level.MethodsWe have calculated ePTpc in humans by urine P and creatinine concentration, with the end-proximal tubule fluid volume calculated either as lithium (Li) clearance (ePTpc-Li) or as a fixed 0.7 fraction of glomerular filtration rate (GFR), as published (ePTpc-70). Healthy people undergoing living transplant kidney donation before (DON-pre, n = 70) and after (DON-post, n = 64) nephrectomy and 25 patients with stage 2–5 CKD were investigated while on regular free diet.ResultsePTpc showed a stepwise increase with decreasing functional renal mass (DON-pre 2.51 ± 0.99 and 1.56 ± 0.47 mg/dL for ePTpc-Li and -70 calculation, respectively; DON-post 3.43 ± 1.14 and 2.18 ± 0.44; CKD 5.68 ± 3.30 and 3.00 ± 1.30, P &lt; .001 for all); ePTpc was inversely correlated with Ccr and directly with PTH, fractional P excretion and excretion (UpV) corrected for GFR (P &lt; .001 for all), but not with Pp. ePTpc-Li and ePTpc-70 were significantly correlated (r = 0.62, P &lt; .001), but ePTpc-70 was lower than the corresponding ePTpc-Li. Levels of ePTpc increased above a suggested dangerous threshold when daily UpV/GFR was higher than about 10 mg/mLCcr.ConclusionsePTpc progressively increases in humans as functional renal mass falls independently from plasma P levels. Main determinants of ePTpc rise are GFR fall, degree of phosphaturia per unit GFR and P intake corrected for GFR. It may become a novel, potentially useful, indicator to guide management of CKD patients.
Lung toxicity of lomustine in the treatment of progressive gliomas
Authors: Seliger Corinna , Nürnberg Christina , Wick Wolfgang , Wick Antje 
Published: May 2022

Abstract

Background
Pulmonary fibrosis is a rare, but dangerous side effect of CCNU (lomustine). CCNU is a frequently used chemotherapeutic agent in the setting of recurrent or progressive glioblastoma. At present, CCNU is also administered in patients with newly diagnosed gliomas in combination with temozolomide. There is only little evidence if, and how, lung function should be monitored on treatment with CCNU.

Methods
We retrospectively collected data on patient characteristics, lung function analyses, and relevant toxicities among 166 brain tumor patients treated with CCNU at a German University Hospital and National Cancer Center.

Results
The patient collective mainly included patients with recurrent glioblastoma who received a mean number of 2.64 ± 1.57 cycles. There was overall no statistically significant change in parameters of pulmonary restriction among patients treated with CCNU. On an individual patient basis, a &gt;10% decrease in the absolute vital capacity was primarily seen in patients with prior lung diseases and smokers. Other severe toxicities mainly included thrombocytopenia, leukopenia, nausea, and vomiting.

Conclusions
Our findings support to limit lung function analyses on CCNU to patients with gliomas and pulmonary risk factors. However, all patients should be closely followed for clinical symptoms of pulmonary restriction.
Intrinsically flexible displays: key materials and devices
Authors: Zhao Zhiyuan , Liu Kai , Liu Yanwei , Guo Yunlong , Liu Yunqi 
Published: May 2022

AbstractContinuous progress in flexible electronics is bringing more convenience and comfort to human lives. In this field, interconnection and novel display applications are acknowledged as important future directions. However, it is a huge scientific and technical challenge to develop intrinsically flexible displays due to the limited size and shape of the display panel. To address this conundrum, it is crucial to develop intrinsically flexible electrode materials, semiconductor materials and dielectric materials, as well as the relevant flexible transistor drivers and display panels. In this review, we focus on the recent progress in this field from seven aspects: background and concept, intrinsically flexible electrode materials, intrinsically flexible organic semiconductors and dielectric materials for organic thin film transistors (OTFTs), intrinsically flexible organic emissive semiconductors for electroluminescent devices, and OTFT-driven electroluminescent devices for intrinsically flexible displays. Finally, some suggestions and prospects for the future development of intrinsically flexible displays are proposed.
Skin and respiratory ill-health attributed to occupational face mask use
Authors: Seed M J , Fowler K , Byrne L , Carder M , Daniels S , Iskandar I Y K , Feary J , Gawkrodger D J , van Tongeren M 
Published: May 2022

Abstract

Background
Face mask use in the workplace has become widespread since the onset of the Covid-19 pandemic and has been anecdotally linked to adverse health consequences.

Aims
To examine reports of adverse health consequences of occupational face mask use received by The Health and Occupation Research (THOR) network before and after the pandemic onset.

Methods
THOR databases were searched to identify all cases of ill-health attributed to ‘face mask’ or similar suspected causative agent between 1 January 2010 and 30 June 2021.

Results
Thirty two cases were identified in total, 18 reported by occupational physicians and 14 by dermatologists. Seventy-five per cent of cases were reported after the pandemic onset and 91% cases were in the health and social care sector. 25 of the 35 (71%) diagnoses were dermatological, the most frequent diagnoses being contact dermatitis (14 cases) and folliculitis/acne (6 cases). Of the seven respiratory diagnoses, four were exacerbation of pre-existing asthma.

Conclusions
There is evidence of an abrupt increase in reports of predominantly dermatological ill-health attributed to occupational face mask use since the start of the pandemic. Respiratory presentations have also occurred.
Management of Acral and Mucosal Melanoma: Medical Oncology Perspective
Authors: Jung Seungyeon , Johnson Douglas B 
Published: May 2022

AbstractAcral and mucosal melanomas (MM) are rare subtypes of melanoma that are biologically and clinically distinct from cutaneous melanoma. Despite the progress in the treatment of cutaneous melanomas with the development of targeted and immune therapies, the therapeutic options for these less common subtypes remain limited. Difficulties in early diagnosis, the aggressive nature of the disease, and the frequently occult sites of origin have also contributed to the poor prognosis associated with acral and MM, with substantially worse long-term prognosis. The rarity of these subtypes has posed significant barriers to better understanding their biological features and investigating novel therapies. Consequently, establishing standardized treatment guidelines has been a challenge. In this review, we provide a brief overview of the current knowledge regarding acral and MM, focusing on their epidemiology, genetic backgrounds, and unique clinical characteristics. Further discussion centers around the management of primary and advanced disease and the role of emerging targeted and immune therapies for these subtypes, specifically focusing on issues relevant to medical oncologists.
Sleep restriction and age effects on waking alpha EEG activity in adolescents
Authors: Campbell Ian G , Kim Elizabeth I , Darchia Nato , Feinberg Irwin 
Published: May 2022

AbstractStudy ObjectivesTo understand how sleep need changes across adolescence our laboratory is carrying out a longitudinal dose–response study on the effects of sleep duration on daytime sleepiness and performance. This report focuses on the relation of the waking alpha (8–12 Hz) electroencephalogram (EEG) to prior sleep duration, whether this relation changes with age, and whether decreased waking alpha power is related to changes in daytime sleepiness, vigilance, and executive functioning.MethodsStudy participants (n = 77) entered the study at ages ranging from 9.86 to 13.98 years and were studied annually for 3 years. Each year participants completed each of three time in bed (TIB) conditions (7, 8.5, or 10 h) for four consecutive nights. Waking EEG was recorded on the day following the fourth night.ResultsTIB restriction and resultant sleep loss were associated with reduced alpha power with the effect being stronger for the eyes closed condition. TIB restriction altered the power spectrum within the alpha range by increasing the frequency of maximum alpha power. Alpha power decreased with age, but the effect of TIB restriction did not decrease with age. Reduced alpha power was associated with small but significant increases in subjective and objective sleepiness but was not associated with changes in vigilance or executive functioning.ConclusionsWe interpret the alpha depression following sleep loss as incomplete sleep dependent recuperation that contributes to daytime sleepiness. The absence of a decrease in TIB effects with age indicates that this sleep need measure does not decrease over early to mid-adolescence.
Evidence for Elicitation of an Oxidative Burst in Vitis vinifera by Xylella fastidiosa Cold Shock Protein Peptide csp20
Authors: Burbank Lindsey P. , Ochoa Joanna 
Published: May 2022

Plant response to pathogen challenge involves recognition by specific receptors of conserved molecular patterns associated with pathogenic organisms. Understanding a wider range of pathogen detection pathways in different plant species is valuable for identification and development of pathogen-resistant plant material. Xylella fastidiosa is an important bacterial pathogen of several agricultural crops including table and wine grapes. Although some pathogen recognition pathways have been identified for X. fastidiosa in host plants, there are likely several other molecular interactions that could be exploited to increase plant resistance to this pathogen. This study identified a conserved bacterial cold shock protein component (Xfcsp20) as an elicitor of reactive oxygen species production by Vitis vinifera plant tissue, an indication of pathogen recognition response. Characterization of Xfcsp20 as an elicitor of an oxidative burst in grapevine hosts of X. fastidiosa will be useful to continued work in the areas of bacterial-plant interactions and plant resistance. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Influence of Deep Serratus Anterior Plane Block on Chronic Pain at 3 Months After Breast-Conserving Surgery
Authors: Fuzier Régis , Salvignol Geneviève , Gilbert Olivier , Bremaud Marc , Bataille Benoît , Izard Philippe 
Published: May 2022

Objectives:
In 2015, we evaluated our practices regarding pain after breast-conserving surgery. Thereafter, we have adapted our practices by performing a systematic deep serratus plane block before the surgical incision. In 2019, we assessed the impact of these changes in terms of chronic pain. The main objective of this study was to evaluate the prevalence of chronic pain 3 months after this type of surgery.

Materials and Methods:
All patients treated with breast-conserving surgery as outpatients were included in this prospective study between April and July 2019. After inducing general anesthesia, 20 mL of ropivacaine 3.75 mg/mL were injected under the serratus muscle. Morphine titration was performed in the recovery room according to pain scores. A pain and quality of life questionnaire was sent 3 months after surgery. A backward logistic regression model was applied to calculate the adjusted odds ratios.

Results:
The final analysis involved 137 patients. Three months after surgery, 43 patients (31%) reported persistent pain related to the surgery. Maximum pain in the last 24 hours was moderate to severe in 60% of cases, 16 patients (35%) took painkillers. Morphine titration in the recovery room was required in 25 patients (18%). Younger age and the use of lidocaine to prevent after injection of propofol during general anesthesia induction appeared to be protective factors for the risk of pain at 3 months (secondary endpoints).

Discussion:
No persistent pain at 3 months was reported in 69% of cases. Furthermore, the use of a deep serratus anterior plane block before the surgical incision has limited the need for morphine titration in the recovery room to <1 patient in 5. These evaluations of professional practices should be encouraged.
Geriatric Falls: A Registry-Based Study in the Netherlands
Authors: Verbeek Frank H. O. , Ham Wietske H. W. , Verbeek André L. M. , de Man-van Ginkel Janneke M. , van Os-Medendorp Harmieke , Westers Paul , Leenen Luke P. H. 
Published: May 2022

BACKGROUND:
Falls in people 65 years and older evaluated in the emergency department are increasing. Of all unintentional injury-related deaths among older people, 55% are due to falls. The impact of falls, especially concerning Dutch older people with the highest proportion of living independently worldwide, is unclear.

OBJECTIVE:
To identify the influence of age, gender, health conditions, and type of fall on the severity of injury, hospital length of stay, mortality, and discharge destination.

METHODS:
A total number of 6,084 patients from a comprehensive regional trauma care system, 65 years and older and hospitalized after a fall, were included. Groups were compared for patient-related factors and multivariable logistic regression analysis to explore the consequences.

RESULTS:
Mean age was 82 years (SD = 8.3), and 70% were female. Most falls (66.4%) were due to “slipping and tripping” or “falls on the same level,” 57.4% had Injury Severity Scores between 9 and 12, and 43.3% were discharged home. Higher age and type of fall increased the likelihood of severe injuries. Men experienced shorter hospital stays than women and were less frequently discharged home. Mortality was higher in males (10.8%) than in females (6.7%) and increased with the American Society of Anesthesiologists scores for preexisting health conditions.

CONCLUSION:
Advanced age, gender, type of fall, and prior health status play a significant role in the severity of injuries, length of hospital stay, 30-day mortality, and higher discharge destination to care homes in older people hospitalized after a fall.
Evaluation of Stop the Bleed Training Among High School Personnel: A Qualitative Study
Authors: Jones Allison R. , Strickland Virginia , Brown Michelle R. 
Published: May 2022

BACKGROUND:
Uncontrolled hemorrhage is the primary preventable cause of death following trauma. Stop the Bleed training exists to promote identification and basic treatment of life-threatening bleeding in the prehospital or community setting. Limited qualitative research is available on participant evaluation of hemorrhage control training for laypersons.

OBJECTIVE:
To evaluate the experience and satisfaction with Stop the Bleed training among lay community members in an urban public school setting.

METHODS:
Three group interviews were conducted with public high school personnel (faculty and staff) who received Stop the Bleed training. Personnel were asked to evaluate the training and provide suggestions for improvement. Responses were digitally recorded and transcribed verbatim. Content analysis for common themes was performed using NVivo.

RESULTS:
A total of eight participants were interviewed. Participants expressed satisfaction with hands-on training and dissatisfaction with crowded and rushed training conditions. Major themes included: (1) skill acquisition, retention, and decay, (2) training format and setting, and (3) use of simulation.

CONCLUSIONS:
Current Stop the Bleed training is considered satisfactory among public school educators. Suggestions for improvement include annual retraining programs and simulation-enhanced training opportunities.