bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective impairment of circuits between prefrontal cortex glutamatergic neurons and basal forebrain cholinergic neurons in a tauopathy mouse model
Authors: Zhong Ping , Cao Qing , Yan Zhen
Published: February 2022

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder linked to cognitive decline. To understand how specific neuronal circuits are impaired in AD, we have used optogenetic and electrophysiological approaches to reveal the functional changes between prefrontal cortex (PFC) and basal forebrain (BF), 2 key regions controlling cognitive processes, in a tauopathy mouse model. We found that the glutamatergic synaptic responses in BF cholinergic neurons from P301S Tau mice (6–8 months old) were markedly diminished. The attenuated long-range PFC to BF pathway in the AD model significantly increased the failure rate of action potential firing of BF cholinergic neurons triggered by optogenetic stimulations of glutamatergic terminals from PFC. In contrast, the projection from PFC to other regions, such as amygdala and striatum, was largely unaltered. On the other hand, optogenetic stimulation of cholinergic terminals from BF induced a persistent reduction of the excitability of PFC pyramidal neurons from Tau mice, instead of the transient reduction exhibited in wild-type mice. Taken together, these data have revealed a selective aberration of the pathway between PFC pyramidal neurons and BF cholinergic neurons in a tauopathy mouse model. This circuit deficit may underlie the loss of attention and executive function in AD.
Micellar Thin Layer Chromatography and Computer-Aided Analysis of Empagliflozin, Linagliptin and Metformin HCl Ternary Mixture
Authors: Abbas Noha S , Mohamed Yahya Abduh Salim , Derayea Sayed M , Omar Mahmoud A , Saleh Gamal A
Published: February 2022

The present work was performed in order to study the mechanism of micellar thin layer chromatography (MTLC) and to develop a new simple and sensitive simultaneous MTLC method for separation of empagliflozin, Linagliptin and metformin hydrochloride ternary mixture. The study was done using three different surfactants; sodium dodecyl sulphate (SDS), benzalkonium chloride (BAC) and polysorbate 80 (tween 80). Chromatographic procedure was performed using micellar mobile phase that composed of aqueous solution of each surfactant and methanol (6: 4 v/v) and micellar TLC determination at λmax 237 nm. Separation using SDS (anionic surfactant) and BAC (cationic surfactant) depends on ionization potential (AMI-IP), partition coefficient (logP (o/w)) and hydrogen bond donor atoms (a-don), whereas separation using tween 80 depends mainly on the lipophilicity (RM0), solvation energy (E-sol) and Van der Waals energy (E-vdw). Quantitative structure–retention relationships study was carried out, modeled, evaluated and validated using molecular operating environment software.
Screening and Identification of Croton Fruit Poisoning in Food Using GC–MS and HPLC–MS/MS
Authors: Chen Dongyang , Li Tanyao , Fan Xiang , Li Bangrui , Zhang Hao , Zeng Dong , Feng Jiali , Jiang Dingguo
Published: February 2022

Croton fruit poisoning was successfully identified through a series of chromatographic technologies. A suspected compound named 2-methyl-butenoic acid was screened out using gas chromatography–mass spectrometry, and the hydrolysate of isoguanosine in soup sample was further detected by high performance liquid chromatography–tandem mass spectrometry. The identification of croton fruit poisoning was confirmed basing on these laboratory tests together with the clinical symptoms of the patients. Especially, the false-negative result and the interferences were successfully excluded through simulation test, spectral analysis and chromatographic separation technique. Such study is significant for croton poisoning identification and provides beneficial references for disposing untargeted food poisoning incident.
What Can IBD Specialists Learn from IL-23 Trials in Dermatology?
Authors: Valenti Mario , Narcisi Alessandra , Pavia Giulia , Gargiulo Luigi , Costanzo Antonio
Published: February 2022

Background and Aims

The advent of biologic drugs revolutionised the treatment of many chronic inflammatory diseases in rheumatology, dermatology, and gastroenterology. The introduction of different targeted agents closely followed the increase in knowledge of pathogenic mechanisms. The identification of IL-23 as a master regulator of ‘pathogenic’ inflammation and the consequent efficacy of IL-23 blocking agents were first proofed in psoriasis and then in other inflammatory diseases such as psoriatic arthritis and Crohn’s disease.

Methods

We reviewed all available results from anti-Il-23 clinical trials for psoriasis, focusing on data of IBDologists’ interest. Regarding guselkumab, we analysed data from phase III clinical trials VOYAGE1, VOYAGE2, and NAVIGATE. For risankizumab, we reported efficacy and safety results from UltIMMa-1, UltIMMa-2, and IMMvent clinical trials, and tildrakizumab was evaluated by analysing data from reSURFACE1 and reSURFACE2 studies.

Results

Data from all the clinical trials that we reported showed both the efficacy of all three anti-IL-23 drugs in psoriasis and the safety of this class; in particular, no gastrointestinal side effects were observed in those studies. IL-23 blockers have shown promising short- and long-term results in psoriasis, with a major safety profile and no negative interactions with gastrointestinal system.

Conclusions

Anti-IL-23 indication for psoriatic arthritis is very recent and for IBD is still to come. Therefore, dermatologists are accumulating long-term experience with these drugs, both in clinical trials and in real-world evidence, which can help gastroenterologists in the management of IBD patients.
Tailoring Multi-omics to Inflammatory Bowel Diseases: All for One and One for All
Authors: Sudhakar Padhmanand , Alsoud Dahham , Wellens Judith , Verstockt Sare , Arnauts Kaline , Verstockt Bram , Vermeire Severine
Published: February 2022

Inflammatory bowel disease [IBD] has a multifactorial origin and originates from a complex interplay of environmental factors with the innate immune system at the intestinal epithelial interface in a genetically susceptible individual. All these factors make its aetiology intricate and largely unknown. Multi-omic datasets obtained from IBD patients are required to gain further insights into IBD biology. We here review the landscape of multi-omic data availability in IBD and identify barriers and gaps for future research. We also outline the various technical and non-technical factors that influence the utility and interpretability of multi-omic datasets and thereby the study design of any research project generating such datasets. Coordinated generation of multi-omic datasets and their systemic integration with clinical phenotypes and environmental exposures will not only enhance understanding of the fundamental mechanisms of IBD but also improve therapeutic strategies. Finally, we provide recommendations to enable and facilitate generation of multi-omic datasets.
Proteasome activity modulates amyloid toxicity
Authors: Galvin John , Curran Elizabeth , Arteaga Francisco , Goossens Alicia , Aubuchon-Endsley Nicki , McMurray Michael A , Moore Jeffrey , Hansen Kirk C , Chial Heidi J , Potter Huntington , Brodsky Jeffrey L , Coughlan Christina M
Published: February 2022

Alzheimer's disease (AD) is responsible for 60%–80% of identified cases of dementia. While the generation and accumulation of amyloid precursor protein (APP) fragments is accepted as a key step in AD pathogenesis, the precise role of these fragments remains poorly understood. To overcome this deficit, we induced the expression of the soluble C-terminal fragment of APP (C99), the rate-limiting peptide for the generation of amyloid fragments, in yeast that contain thermosensitive mutations in genes encoding proteasome subunits. Our previous work with this system demonstrated that these proteasome-deficient yeast cells, expressing C99 when proteasome activity was blunted, generated amyloid fragments similar to those observed in AD patients. We now report the phenotypic repercussions of inducing C99 expression in proteasome-deficient cells. We show increased levels of protein aggregates, cellular stress and chaperone expression, electron-dense accumulations in the nuclear envelope/ER, abnormal DNA condensation, and an induction of apoptosis. Taken together, these findings suggest that the generation of C99 and its associated fragments in yeast cells with compromised proteasomal activity results in phenotypes that may be relevant to the neuropathological processes observed in AD patients. These data also suggest that this yeast model should be useful for testing therapeutics that target AD-associated amyloid, since it allows for the assessment of the reversal of the perturbed cellular physiology observed when degradation pathways are dysfunctional.
A novel mistranslating tRNA model in Drosophila melanogaster has diverse, sexually dimorphic effects
Authors: Isaacson Joshua R , Berg Matthew D , Charles Brendan , Jagiello Jessica , Villén Judit , Brandl Christopher J , Moehring Amanda J
Published: February 2022

Transfer RNAs (tRNAs) are the adaptor molecules required for reading the genetic code and producing proteins. Transfer RNA variants can lead to genome-wide mistranslation, the misincorporation of amino acids not specified by the standard genetic code into nascent proteins. While genome sequencing has identified putative mistranslating transfer RNA variants in human populations, little is known regarding how mistranslation affects multicellular organisms. Here, we create a multicellular model of mistranslation by integrating a serine transfer RNA variant that mistranslates serine for proline (tRNAUGG,G26ASer) into the Drosophila melanogaster genome. We confirm mistranslation via mass spectrometry and find that tRNAUGG,G26ASer misincorporates serine for proline at a frequency of ∼0.6% per codon. tRNAUGG,G26ASer extends development time and decreases the number of flies that reach adulthood. While both sexes of adult flies containing tRNAUGG,G26ASer present with morphological deformities and poor climbing performance, these effects are more pronounced in female flies and the impact on climbing performance is exacerbated by age. This model will enable studies into the synergistic effects of mistranslating transfer RNA variants and disease-causing alleles.
External rectal prolapse: abdominal or perineal repair for men? A retrospective cohort study
Authors: Hu Bang , Zou Qi , Xian Zhenyu , Su Dan , Liu Chao , Lu Li , Luo Minyi , Chen Zixu , Cai Keyu , Gao Han , Peng Hui , Cao Wuteng , Ren Donglin
Published: February 2022

Background

External rectal prolapse is a relatively rare disease, in which male patients account for a minority. The selection of abdominal repair or perineal repair for male patients has rarely been investigated.

Methods

Fifty-one male patients receiving abdominal repair (laparoscopic ventral rectopexy) or perineal repair (Delorme or Altemeier procedures) at the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between March 2013 and September 2019 were retrospectively analysed. We compared the recurrence, complication rate, post-operative defecation disorder, length of stay, and quality of life between the abdominal and perineal groups.

Results

Of the 51 patients, 45 had a complete follow-up, with a median of 48.5 months (range, 22.8–101.8 months). A total of 35 patients were under age 40 years. The complication rate associated with abdominal repair was less than that associated with perineal repair (0% vs 20.7%, P = 0.031) and the recurrence rate was also lower (9.5% vs 41.7%, P = 0.018). Multivariate analysis showed that perineal repair (odds ratio, 9.827; 95% confidence interval, 1.296–74.50; P = 0.027) might be a risk factor for recurrence. Moreover, only perineal repair significantly improved post-operative constipation status (preoperative vs post-operative, 72.4% vs 25.0%, P = 0.001). There was no reported mortality in either of the groups. No patient's sexual function was affected by the surgery.

Conclusions

Both surgical approaches were safe in men. Compared with perineal repair, the complication rate and recurrence rate for abdominal repair were lower. However, perineal repair was better able to correct constipation.
ccd-5, a novel cdk-5 binding partner, regulates pioneer axon guidance in the ventral nerve cord of Caenorhabditis elegans
Authors: Feresten Abigail H , Bhat Jaffar M , Yu Alex J , Zapf Richard , Safi Hamida , Au Vinci , Flibotte Stephane , Doell Claudia , Moerman Donald G , Hawkins Nancy , Rankin Catharine H , Hutter Harald
Published: February 2022

During nervous system development, axons navigate complex environments to reach synaptic targets. Early extending axons must interact with guidance cues in the surrounding tissue, while later extending axons can interact directly with earlier “pioneering” axons, “following” their path. In Caenorhabditis elegans, the AVG neuron pioneers the right axon tract of the ventral nerve cord. We previously found that aex-3, a rab-3 guanine nucleotide exchange factor, is essential for AVG axon navigation in a nid-1 mutant background and that aex-3 might be involved in trafficking of UNC-5, a receptor for the guidance cue UNC-6/netrin. Here, we describe a new gene in this pathway: ccd-5, a putative cdk-5 binding partner. ccd-5 mutants exhibit increased navigation defects of AVG pioneer as well as interneuron and motor neuron follower axons in a nid-1 mutant background. We show that ccd-5 acts in a pathway with cdk-5, aex-3, and unc-5. Navigation defects of follower interneuron and motoneuron axons correlate with AVG pioneer axon defects. This suggests that ccd-5 mostly affects pioneer axon navigation and that follower axon defects are largely a secondary consequence of pioneer navigation defects. To determine the consequences for nervous system function, we assessed various behavioral and movement parameters. ccd-5 single mutants have no significant movement defects, and nid-1 ccd-5 double mutants are less responsive to mechanosensory stimuli compared with nid-1 single mutants. These surprisingly minor defects indicate either a high tolerance for axon guidance defects within the motor circuit and/or an ability to maintain synaptic connections among commonly misguided axons.
Patient satisfaction with pharmaceutical care services for chronic diseases and their medication adherence during COVID-19 in Saudi Arabia
Authors: Lucca Jisha M , Kurdi Sawsan , Albaqshi Batool , Joseph Royes
Published: February 2022

Objectives

During the ongoing coronavirus 2019 (COVID-19) pandemic, chronic disease management and medication adherence have become challenging; thus, health-related quality of life may have been compromised. As highly trusted healthcare providers, pharmacies in Saudi Arabia have undergone restructuring or redesign to cope with the current demands during the pandemic. The study assessed satisfaction levels of patients with chronic diseases concerning pharmaceutical care services provided during COVID-19 in addition to medication adherence and quality of life during the pandemic.

Methods

An online questionnaire-based cross-sectional study was administered. Saudi residents suffering from chronic diseases and receiving pharmaceutical care from a hospital or community pharmacy during the COVID-19 pandemic were eligible. The survey was created using Google Forms and distributed through online channels. The survey targeted 385 participants.

Key findings

A sample of 317 patients was included. More than half had missed a follow-up visit for their chronic conditions since the beginning of the pandemic. The overall mean score ± standard deviation for the satisfaction level with pharmaceutical care services was 22.0 ± 10.3 on a scale of 0–36 with different satisfaction levels for different services. In addition to a good level of medication adherence, a high percentage of these patients reported no problem in most of the dimensions of the EQ-5D scale.

Conclusions

Pharmacists should take a more proactive and consultive role to deliver healthcare needs of patients with a chronic condition and be aware of patient expectations from a pharmacist in situations, such as the current pandemic.
Hepatitis B Virus (HBV) Upregulates TRAIL-R3 Expression in Hepatocytes Resulting in Escape From Both Cell Apoptosis and Suppression of HBV Replication by TRAIL
Authors: Suehiro Yosuke , Tsuge Masataka , Kurihara Mio , Uchida Takuro , Fujino Hatsue , Ono Atsushi , Yamauchi Masami , Naswa Makokha Grace , Nakahara Takashi , Murakami Eisuke , Abe-Chayama Hiromi , Kawaoka Tomokazu , Miki Daiki , Imamura Michio , Aikata Hiroshi , Nelson Hayes C , Fujita Takashi , Chayama Kazuaki
Published: February 2022

Background

Hepatitis B virus (HBV) evades host immunity by regulating intracellular signals. To clarify this immune tolerance mechanism, we performed gene expression analysis using HBV-infected humanized mouse livers.

Methods

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 3 (TRAIL-R3) was significantly upregulated in livers of HBV-infected human hepatocyte transplanted mice by cDNA microarray and next-generation sequencing. We analyzed the significance of TRAIL-R3 upregulation in HBV infection using human hepatocyte transplanted mice and HepG2 cell lines.

Results

TRAIL-R3 induction by HBV infection was verified by in vitro and in vivo HBV replication models, and induction was inhibited by antiviral nucleot(s)ide analogue treatment. TRAIL-R3 transcription was regulated by the TRAIL-R3 promoter at −969 to −479 nucleotides upstream from the transcription start site, and by hepatitis B x (HBx) via activation of nuclear factor-κB (NF-κB) signal. TRAIL not only induced cell apoptosis but also inhibited HBV replication. TRAIL-R3 upregulation could inhibit both TRAIL-dependent apoptosis in HBV-infected hepatocytes and TRAIL-mediated suppression of HBV replication.

Conclusions

These results suggest a mechanism by which HBV persists by escaping host immunity through upregulation of TRAIL-R3. Development of novel drugs to inhibit this escape system might lead to complete HBV elimination from human hepatocytes.
Diurnal shift of mouse activity by the deficiency of an ageing-related gene Lmna
Authors: Kawakami Satoshi , Yoshitane Hikari , Morimura Taiki , Kimura Wataru , Fukada Yoshitaka
Published: February 2022

Nuclear lamina is a fundamental structure of the cell nucleus and regulates a wide range of molecular pathways. Defects of components of the nuclear lamina cause ageing-like physiological disorders, called laminopathy. Generally, ageing and diseases are often associated with perturbation of various time-of-day–dependent regulations, but it remains elusive whether laminopathy induces any changes of the circadian clock and physiological rhythms. Here, we demonstrated that deficiency of Lmna gene in mice caused an obvious shift of locomotor activities to the daytime. The abnormal activity profile was accompanied by a remarkable change in phase angle between the central clock in the suprachiasmatic nucleus (SCN) and the lung peripheral clocks, leaving the phase of the SCN clock unaffected by the mutation. These observations suggest that Lmna deficiency causes a change of the habitat from nocturnal to diurnal behaviours. On the other hand, molecular oscillation and its phase resetting mechanism were intact in both the Lmna-deficient cells and progeria-mimicking cells. Intriguingly, high-fat diet feeding extended the short lifespan and ameliorated the abnormalities of the behaviours and the phase of the peripheral clock in the Lmna-deficient mice. The present study supports the important contribution of the energy conditions to a shift between the diurnal and nocturnal activities.
In vitro and in vivo antihyperglycemic activity of the ethanol extract of Heritiera fomes bark and characterization of pharmacologically active phytomolecules
Authors: Ansari Prawej , Azam Shofiul , Seidel Veronique , Abdel-Wahab Yasser H A
Published: February 2022

Objective

This study aimed to demonstrate the mechanistic basis of Heritiera fomes, which has traditionally been used to treat diabetes.

Methods

Clonal pancreatic β-cells and primary islets were used to measure insulin release. 3T3-L1 cells were used to analyse insulin action, and in vitro systems were used to measure further glucose-lowering activity. In vivo assessment was performed on streptozotocin (STZ)-induced type-2 diabetic rats and reversed-phase-HPLC followed by liquid chromatography mass spectrometry (LC-MS) to detect bioactive molecules.

Key findings

Ethanol extract of Heritiera fomes (EEHF) significantly increased insulin release with stimulatory effects comparable to 1 µM glucagon-like peptide 1, which were somewhat reduced by diazoxide, verapamil and calcium-free conditions. Insulin release was stimulated by tolbutamide, isobutyl methylxanthine and KCl. EEHF induced membrane depolarization and increased intracellular Ca2+ levels. EEHF enhanced glucose uptake in 3T3L1 cells and decreased protein glycation. EEHF significantly inhibited postprandial hyperglycaemia following sucrose loading and inversely elevated unabsorbed sucrose concentration in the gut. It suppressed glucose absorption during in situ gut perfusion. Furthermore, EEHF improved glucose tolerance, plasma insulin and gut motility, and decreased plasma dipeptidyl peptidase IV activity. Procyanidins, epicatechin and proanthocyanidins were some of the identified bioactive constituents that may involve in β-cell actions.

Conclusions

This study provides some evidence to support the use of H. fomes as an antidiabetic traditional remedy.
What drives galaxy quenching? A deep connection between galaxy kinematics and quenching in the local Universe
Authors: Brownson Simcha , Bluck Asa F L , Maiolino Roberto , Jones Gareth C
Published: February 2022

We develop a 2D inclined rotating disc model, which we apply to the stellar velocity maps of 1862 galaxies taken from the MaNGA survey (SDSS public Data Release 15) . We use a random forest classifier to identify the kinematic parameters that are most connected to galaxy quenching. We find that kinematic parameters that relate predominantly to the disc (such as the mean rotational velocity) and parameters that characterize whether a galaxy is rotation- or dispersion-dominated (such as the ratio of rotational velocity to velocity dispersion) are not fundamentally linked to the quenching of star formation. Instead, we find overwhelmingly that it is the absolute level of velocity dispersion (a property that relates primarily to a galaxy’s bulge/spheroidal component) that is most important for separating star-forming and quenched galaxies. Furthermore, a partial correlation analysis shows that many commonly discussed correlations between galaxy properties and quenching are spurious, and that the fundamental correlation is between quenching and velocity dispersion. In particular, we find that at fixed velocity dispersion, there is only a very weak dependence of quenching on the disc properties, whereby more discy galaxies are slightly more likely to be forming stars. By invoking the tight relationship between black hole mass and velocity dispersion, and noting that black hole mass traces the total energy released by active galactic nuclei (AGNs), we argue that these data support a scenario in which quenching occurs by preventive feedback from AGNs. The kinematic measurements from this work are publicly available.
Combining Guided Intervention of Education and Relaxation (GIER) with Remote Electrical Neuromodulation (REN) in the Acute Treatment of Migraine
Authors: Buse Dawn C , Rabany Liron , Lin Tamar , Ironi Alon , Connelly Mark A , Bickel Jennifer L
Published: February 2022

Background

Evidence indicates that combining behavioral treatments with pharmacological treatments for migraine prevention improves efficacy, but little is known about the outcomes of combining neuromodulation and behavioral interventions for acute treatment of migraine. Remote electrical neuromodulation (REN) is a U.S. Food and Drug Administration (FDA)–cleared nonpharmacological migraine treatment. The present study evaluated the clinical benefits of augmenting REN treatment with a specially tailored behavioral therapy consisting of Guided Intervention of Education and Relaxation (GIER) for the acute treatment of migraine.

Methods

In this two-arm observational study, real-world data were collected from patients across the United States who were using the REN device. Eighty-five migraine patients ≥18 years of age who treated their attacks with REN in parallel with the GIER intervention were individually matched on age and sex with 85 patients who used REN alone. The groups were compared on the proportion of migraine attacks in which they achieved pain relief, pain freedom, improvement of function, and return to normal function, all at 2 hours after treatment.

Results

Data from 170 users were analyzed (85 per group). Compared with the REN-only group, the REN+GIER group displayed a statistically significant higher proportion of patients achieving consistent pain relief (P = 0.008), consistent improvement in function (P = 0.014), and consistent return to normal function (P = 0.005), all at 2 hours after treatment.

Conclusions

The results suggest that combining the GIER behavioral intervention with REN treatment can improve the therapeutic efficacy beyond that of REN alone, in terms of both pain level and improvement of disability.
Isotonitazene, a novel psychoactive substance opioid, detected in two cases following a local surge in opioid overdoses
Authors: De Baerdemaeker K S C , Dines A M , Hudson S , Sund L J , Waters M L , Hunter L J , Blundell M S , Archer J R H , Wood D M , Dargan P I
Published: February 2022

Background

Isotonitazene is a novel opioid that was first reported in Europe in 2019. There have been no reports of the detection of isotonitazene in patients presenting to the emergency department with acute drug toxicity.

Aim

There was an increase in presentations to our emergency department with acute opioid toxicity in August 2021. We aim to describe this outbreak and provide detail on two cases in which isotonitazene was quantified in serum samples.

Methods

Serum samples were available for comprehensive toxicological analysis for two presentations. Written consent was obtained and the samples were analysed through a Thermo XRS ultrahigh-performance liquid chromatography system, interfaced to a Thermo Q Exactive high-resolution accurate mass spectrometer, operating in heated positive ion electrospray mode. Acquired data were processed using Toxfinder software (Thermo) against a regularly updated in-house database.

Results

There was an increase in acute opioid presentations to our emergency department from a median of 10 per month to 36 in August 2021. Twenty were treated with naloxone, and 23 were admitted to the hospital for observation and treatment. Serum sample analysis from two patients with acute opioid toxicity responsive to naloxone detected the presence of isotonitazene (0.18 and 0.81 ng/ml).

Conclusion

We report a cluster of acute opioid toxicity presentations to our Emergency Department with detection of isotonitazene in two cases. Analytical screening is important in determining the presence of novel psychoactive substances (NPS) and to help inform the public health of the implications of NPS use, particularly during clusters of acute recreational drug toxicity presentations.
Anti-Ro52 antibodies are associated with the prognosis of adult idiopathic inflammatory myopathy-associated interstitial lung disease
Authors: Gui Xianhua , Shenyun Shi , Ding Hui , Wang Rujia , Tong Jingzhi , Yu Min , Zhao Tingting , Ma Miao , Ding Jingjing , Xin Xiaoyan , Qiu Yuying , Qiu Xiaohua , Zhang Yingwei , Cao Min , Huang Mei , Cao Mengshu , Dai Jinghong , Cai Hourong , Xiao Yonglong
Published: February 2022

Objectives

In the present study, we aimed to assess the prevalence and clinical significance of anti-Ro52 antibodies in a cohort of patients with idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) with different myositis-specific autoantibodies (MSAs).

Methods

A cohort of 267 IIM-ILD patients, including 62 patients with PM, 126 patients with DM and 79 patients with clinically amyopathic DM (CADM) were retrospectively analysed in this study. Clinical and laboratory findings, pulmonary function tests (PFTs), HRCT patterns and treatment information were compared between patients with and without anti-Ro52 antibodies. The association between prognosis and anti-Ro52 antibodies was also evaluated based on different MSA subgroups.

Results

Anti-Ro52 antibodies were more frequent in patients with anti-MDA5 (62.1%, P < 0.01) and anti-Jo1 (64.9%, P < 0.01) antibodies than in those with other MSAs. The proportion of patients with anti-Jo1 antibodies was higher in the anti-Ro52 antibody-positive group than in the anti-Ro52 antibody-negative group. Patients with anti-Ro52 antibodies were more likely to exhibit the Gottron sign than the anti-Ro52 antibody-negative group (P < 0.001). Furthermore, it was a predictive factor for rapid progression interstitial lung disease (RP-ILD) (P = 0.001) and was also associated with a higher mortality rate (log-rank test, P = 0.001). Furthermore, RP-ILD was more frequently exhibited in anti-MDA5- and anti-Ro52-positive patients. Moreover, anti-Ro52 antibody positivity was closely associated with a higher mortality rate in anti-MDA5-ILD patients (log-rank test, P < 0.05).

Conclusions

Anti-Ro52 antibodies were highly prevalent in patients with anti-MDA5 and anti-Jo1 antibodies. Within all patients with IIM-ILD, those with anti-Ro52 autoantibodies had a higher frequency of RP-ILD and a poorer prognosis, especially in the anti-MDA5 antibody subgroup.
MicroRNA-20a-5p regulates the epithelial-mesenchymal transition of human hepatocellular carcinoma by targeting RUNX3
Authors: Wang Xianjue , Wei Ping , Yang Ling , Liu Fangyuan , Tong Xin , Yang Xiaoyu , Su Liya
Published: February 2022

Background:

MicroRNA-20a (miR-20a) is dysregulated in many types of malignancies, including human hepatocellular carcinoma (HCC), but its expression level and functional significance in HCC are still disputed. We aimed to study the role of miR-20a-5p in HCC and its downstream molecular mechanisms.

Methods:

We used real-time polymerase chain reaction to detect the expression of miR-20a-5p and runt-related transcription factor 3 (RUNX3) in HCC and paraneoplastic tissue, transfected Huh7 and highly metastatic human hepatocellular carcinoma (MHCC97H) cells. A live cell workstation was used to observe the proliferation and migration of transfected cells. The invasiveness of transfected cells was verified by Transwell assay. Cell apoptosis was detected by flow cytometry. The expression levels of proteins after transfection were measured using simple western immunoblot measurements. Gene expression profiles between HCC and normal samples were obtained from The Cancer Genome Atlas. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were processed by the database for annotation, visualization and integrated discovery. Potential target genes of miR-20a-5p were predicted to further investigate how miR-20a-5p regulates epithelial-mesenchymal transition (EMT) in HCC.

Results:

MiR-20a-5p was significantly highly expressed in HCC tissues, and overexpression of miR-20a-5p significantly promoted HCC cell proliferation, migration, and invasion and inhibited apoptosis in vitro. The protein expression of E-cadherin was decreased and that of vimentin was increased after overexpression of miR-20a-5p in HCC cells. We discovered the intersection of genes from miRDB, miR TarBase, and TargetScan, obtained 397 target genes and finally focused on RUNX3. RUNX3 was not only reduced in HCC specimens but also drastically reduced in HCC cells overexpressing miR-20a-5p. RUNX3 expression decreased with elevated miR-20a-5p, which activated downstream EMT signaling and promoted cell proliferation, migration, and invasion.

Conclusions:

Since RUNX3 is involved in EMT in HCC, as proven by previous research, our findings provide further evidence for a novel regulatory pathway comprising the miR-20a/RUNX3/EMT axis that upregulates EMT signaling and enhances the migration of HCC cells.
Perceptions of Safety Around Use of Cannabis and Nicotine/Tobacco in Pregnancy
Authors: Jarlenski Marian , Spencer Noelle
Published: February 2022

The perceived safety of cannabis and nicotine/tobacco use contribute to use of these substances in pregnancy. We assessed time trends in self-reported perception of safety of use of cannabis and nicotine/tobacco among US women of reproductive age. We also reviewed qualitative literature to elucidate factors contributing to the perceived safety of use of cannabis and nicotine/tobacco. US women increasingly perceive cannabis use as posing no health risks; whereas cigarette smoking is perceived as posing substantial health risks. Qualitative studies suggest that personal experiences, sociocultural norms, and environmental factors contribute to the perceived safety of cannabis and nicotine/tobacco use in pregnancy.
It's not only swallowing: a clinician primer to adult food refusal beyond dysphagia
Authors: Kershner Marnie , Askren Annette N.
Published: February 2022

Purpose of review

Medical teams are frequently faced with challenging clinical scenarios when their patients exhibit reduced intake of food and drink. Speech-language pathologists, who serve as oropharyngeal swallowing specialists in medical settings, are frequently the first to be summoned with the referral, ‘Poor PO intake. Please evaluate and treat.’ As our practices have illuminated, many differentials other than oropharyngeal dysphagia are often at play.

Recent findings

Changes to taste, salivary supply/dry mouth, hunger drive, and psychosocial circumstances will significantly impact intake per os – each scenario to be explored further in this paper. Consequences to diminished nutrition and hydration include medical complications, lengthier hospital stays, and diminished quality of life.

In this review, two medical speech-language pathologists detail more common alternative diagnoses that explain reduced intake by mouth amongst adults with acute and chronic diseases. Ultimately, a multidisciplinary approach should be considered when evaluating such patients to ensure a comprehensive and effective care plan.
Clinical Experience of an American Academic Ophthalmology Department During the COVID-19 Pandemic
Authors: Kuo Irene C.
Published: February 2022

Background and Objectives:

To describe the experience of a large American academic ophthalmology department from the start of the COVID-19 pandemic to the early recovery phase in Summer 2020.

Methods:

Retrospective review; description of approaches taken by our academic medical center and department regarding supply chain issues, protection of doctors and staff, elimination of nonurgent care, calls for staff and faculty deployment, and reopening. Comparison of surgical and clinic volumes in suburban locations versus the main campus; analysis of volumes compared with pre-pandemic periods.

Results:

At our medical center, screening and precautions (such as the mask policy) continued to evolve from March through August 2020. Ophthalmologists were not allowed to use N95 respirators except in rare circumstances. Surgical and clinic volume dropped at both urban and suburban locations, but surgery rebounded more quickly at suburban surgery centers once elective procedures resumed. Mandates from administration were not always attainable.

Conclusions:

During respiratory pandemics such as COVID-19, medical centers should adopt protective measures that are consistent across inpatient and outpatient sectors and consistent with other institutions. Our department's large presence outside the urban center where the main hospital is located allowed faster return of clinical care overall. In the event of another pandemic, a central budget rather than individual divisional budgets should be used for purchase of protective equipment for health care workers of an academic center. Because outpatient care provides important continuity of care and keeps patients away from emergency departments and hospitals, perhaps outpatient care does not have to be curtailed to the extent it was in Spring-Summer 2020, provided that outpatient health care workers have sufficient staff and equipment and the above measures are in place.
Circular noncoding RNA circ_0007865, serves as a competing endogenous RNA, targeting the miR-214-3p/FKBP5 axis to regulate oxygen-glucose deprivation-induced injury in brain microvascular endothelial cells
Authors: Liu Jinghua , Zhang Hong , Di Kuiyi , Hou Liying , Yu Shanshan
Published: February 2022

Background

Ischemic stroke (IS) is a major cause of permanent morbidity and lifelong disability worldwide. Circular RNA (circRNA) circ_0007865 has been reported to be upregulated in acute ischemic stroke (AIS) patients. Also, AIS patients exhibited increased death of human brain microvascular endothelial cells (HBMECs). This study is designed to explore the role and mechanism of circ_0007865 in the oxygen-glucose deprivation (OGD)-induced cell damage in AIS.

Methods

Circ_0007865, microRNA-214-3p (miR-214-3p), and FK506-binding protein 5 (FKBP5) levels were detected by real-time quantitative PCR. Cell proliferative angiogenesis, migration, and apoptosis were assessed by Cell Counting Kit-8, 5-ethynyl-2′-deoxyuridine, colony formation, tube formation, wound healing, transwell, and flow cytometry assays. B-cell lymphoma-2 (Bcl-2), Bcl-2-related X protein (Bax), cleaved caspase-3, and FKBP5 protein levels were determined by western blot assay. The binding relationship between miR-214-3p and circ_0007865 or FKBP5 was predicted by StarBase, and verified by a dual-luciferase reporter, RNA pull-down assay.

Results

Circ_0007865 and FKBP5 were increased, and miR-214-3p was decreased in OGD-treated HBMECs. Furthermore, the silencing of circ_0007865 could promote cell proliferative angiogenesis, migration, and inhibit apoptosis in OGD-triggered HBMECs in vitro. Mechanically, circ_0007865 acted as a sponge of miR-214-3p to regulate FKBP5.

Conclusion

According to these results, circ_0007865 deficiency could attenuate OGD-induced HBMEC damage by modulating the miR-214-3p/FKBP5 axis, hinting at a promising therapeutic target for future acute IS therapy.
Results From the REsCue Trial: A Randomized Controlled Trial with Extended-Release Calcifediol in Symptomatic Outpatients with COVID-19
Authors: Bishop Charles W. , Ashfaq Akhtar , Melnick Joel Z. , Vazquez-Escarpanter Enrique , Fialkow Jonathan A. , Strugnell Stephen A. , Choe John , Kalantar-Zadeh Kamyar , Federman Noah C. , Ng David , Adams John S.
Published: February 2022

Importance

The benefit of vitamin D treatment for coronavirus disease 2019 (COVID-19) remains unclear.

Objective

To investigate the effect of raising serum total 25-hydroxyvitamin D (25D) to 50-100 ng/mL with oral extended-release calcifediol (ERC) on time to symptom resolution in mild to moderate COVID-19.

Design, Setting, and Participants

A multicenter, randomized, double-blind, placebo-controlled study evaluated treatment of 160 outpatients with COVID-19 diagnosed between November 2020 and October 2021.

Interventions

Patients were treated for 4 weeks with ERC (30 mcg/capsule; 300 mcg on Days 1-3 and 60 mcg on Days 4-27) or placebo.

Outcome Measures

Primary endpoints were raising serum 25D to ≥50 ng/mL at Day 14 and resolution time for five aggregated symptoms. Secondary endpoints included resolution time for aggregated and individual symptoms as a function of serum 25D and changes in clinical biomarkers.

Results

171 subjects randomized, 160 treated and 134 (65 ERC and 69 placebo) retained. Average age was 43 (range: 18-71); 59% female, 92% White, 80% Hispanic, 7% African-American, 1% Other, 76% overweight, 40% obese, 26% comorbidities, mean baseline 25D of 37±1 (SE) ng/mL. ERC increased mean 25D to 82±4 ng/mL (p<0.001) by Day 7; 88% of subjects attained a level ≥50 ng/mL; the placebo group trended lower. Resolution time for five aggregated symptoms was unchanged by ERC given that two composite non-respiratory symptoms responded poorly. Prespecified analyses showed that respiratory symptoms tended to resolve earlier when serum 25D levels reached ≤50 ng/mL, but statistical significance was limited by small sample size and non-compliance: 25D increased in seven placebo subjects (unauthorized supplementation) and none occurred in five ERC subjects (failure to dose). A post-hoc composite of three respiratory symptoms (trouble breathing, chest congestion and dry or hacking cough) resolved 3.0 days faster when 25D was elevated at Days 7 and 14 (p<0.05); chest congestion resolved 4.0 days faster with 25D increases of ≥25 ng/mL (p<0.05). Safety concerns including hypercalcemia were absent with ERC treatment.

Conclusions and Relevance

ERC was effective in increasing serum 25D in outpatients with COVID-19, which may have accelerated resolution of respiratory symptoms suggesting mitigation of COVID-19 pneumonia risk, findings which warrant further study.
Whole-Brain Map of Top-down afferent Inputs to Nucleus Accumbens of the Mouse
Authors: Xu Tonghui , Wu Jialiang , Chen Zhilong , Li Zhao
Published: February 2022

Nucleus accumbens (NAc) is an important part of basal ganglia and receives major transsynaptic inputs from medial prefrontal cortex (mPFC), basolateral amygdala nucleus (BL) and hippocampus (HPC). The neural circuits formed by mPFC, BL, HPC with NAc are closely related to diverse brain functions such as decision-making, social behavior, reward seeking behavior and aggressive behavior. However, a lack of information about network structure of NAc top-down afference has limited our understanding of mechanisms of these functions. Here, we systematically analyzed whole brain patterns of inputs to mPFC/HPC/BL-NAc projectors via using (TRIO) labeling strategy. We found that the upstream input patterns between mPFC-core and mPFC-shell projections, BL-core and BL-shell projections, HPC-core and HPC-shell projections were similar. The projections from mPFC and BL to NAc receive a wide range of inputs, while the projections from HPC to NAc receive convergent inputs. Furthermore, all of mPFC/HPC/BL-NAc projectors receive considerable inputs from respective local regions. This study lays a foundation for further analysis of complex NAc functional mechanisms.
Interactions between genes altered during cardiotoxicity and neurotoxicity in zebrafish revealed using induced network modules analysis
Authors: Kagoo R Andrea , Sharma Ankush , Bhargava Anamika
Published: February 2022

Zebrafish has become a prominent model organism to study toxicology due to its genomic similarity to humans, optical clarity, well defined developmental stages, short generation time and cost-effective maintenance. It also provides a shorter time frame for in vivo toxicology evaluation compared to mammalian experimental systems. As manufacturing processes and development of new synthetic compounds increase to keep pace with the expanding global demand, environmental health and the effects of toxicant exposure are emerging as critical public health concerns. Owing to this, in this study, we analyzed the impact of such chemical induced toxicity in zebrafish. We first searched the literature comprehensively for genes that were modulated during neurotoxicity and cardiotoxicity in zebrafish and then studied the interactions between those genes using induced network modules analysis of the database ConsensusPathDB. The induced network modules analysis helps to study gene interactions through various types of interactions like gene regulatory, biochemical, genetic and protein interactions. A constant communication between the heart and the brain is an important physiological phenomenon. Therefore, we also analyzed the interactions among genes that are modulated simultaneously during cardiotoxicity and neurotoxicity. This study has led us to identify some potential predictive biomarkers for neurotoxicity and cardiotoxicity in zebrafish.
High rates of spontaneous chromosomal duplications unravel dosage compensation by translational regulation
Authors: Krasovec Marc , Merret Remy , Sanchez Frédéric , Sanchez-Brosseau Sophie , Piganeau Gwenaël
Published: February 2022

While duplications have long been recognized as a fundamental process driving major evolutionary innovations, direct estimations of spontaneous chromosome duplication rates, leading to aneuploid karyotypes, are scarce. Here, we provide the first estimations of spontaneous chromosome duplication rates in six unicellular eukaryotic species from mutation accumulation (MA) experiments. The spontaneous chromosome duplication rates reach 1×10−4to 1×10−3per genome per generation, which is ~4 to ~50 times less frequent than spontaneous point mutations per genome, whereas chromosome duplication events can affect 1 to 7% of the total genome size. Comparative transcriptomics between MA lines with different chromosome duplications reveals a strong positive correlation between RNA expression rate and DNA copy number. However, comparative analyses of the translation rate of mRNAs estimated by polysome profiling unravel a chromosome specific dosage compensation mechanism. In particular, one chromosome with a gene average of 2.1 excess of mRNAs is compensated by an average of ~0.7 decrease in translation rates. Altogether, our results are consistent with previous observations of a chromosome dependent effect of dosage compensation and provide evidence that it may occur during translation. These results support the existence of a yet unknown post-transcriptional mechanism orchestrating the modification of translation of hundreds of transcripts from genes located on duplicated regions in eukaryotes.