bluuebunny/crossref_metadata_2025 huggingface dataset:
How baryons affect haloes and large-scale structure: a unified picture from the Simba simulation
Authors: Sorini Daniele , Davé Romeel , Cui Weiguang , Appleby Sarah
Published: August 2022

Using the state-of-the-art suite of hydrodynamic simulations Simba, as well as its dark-matter-only counterpart, we study the impact of the presence of baryons and of different stellar/AGN feedback mechanisms on large-scale structure, halo density profiles, and on the abundance of different baryonic phases within haloes and in the intergalactic medium (IGM). The unified picture that emerges from our analysis is that the main physical drivers shaping the distribution of matter at all scales are star formation-driven galactic outflows at z > 2 for lower mass haloes and AGN jets at z < 2 in higher mass haloes. Feedback suppresses the baryon mass function with time relative to the halo mass function, and it even impacts the halo mass function itself at the ∼20 per cent level, particularly evacuating the centres and enhancing dark matter just outside haloes. At early epochs baryons pile up in the centres of haloes, but by late epochs and particularly in massive systems gas has mostly been evacuated from within the inner halo. AGN jets are so efficient at such evacuation that at low redshifts the baryon fraction within ∼1012–1013 M⊙ haloes is only 25 per cent of the cosmic baryon fraction, mostly in stars. The baryon fraction enclosed in a sphere around such haloes approaches the cosmic value Ωb/Ωm only at 10–20 virial radii. As a result, 87 per cent of the baryonic mass in the Universe lies in the IGM at z = 0, with 67 per cent being in the form of warm-hot IGM (T > 105K).
A TESS search for donor-star pulsations in high-mass X-ray binaries
Authors: Ramsay Gavin , Hakala Pasi , Charles Philip A
Published: August 2022

Ground-based optical photometry of the counterparts of high-mass X-ray binaries (HMXBs) has revealed the presence of periodic modulations on time-scales of ∼0.3–0.5 d. More recent space-based observations (CoRoT and TESS) of OB and Be stars have shown that pulsations caused by p and g modes are common in early-type stars. We have therefore undertaken a systematic search for variability in the optical counterparts of 23 HMXBs (mostly neutron star systems, but including one black hole, Cyg X-1) using TESS data primarily in 2 min cadence mode. After removing the orbital period modulation in four systems, we find that all 23 sources show evidence for quasi-periodic variability on periods shorter than ∼1 d. We compare their power spectra with those from observations of other OB- and Be-type stars. In two systems, V725 Tau and HD 249179 (which may not be an HMXB), we find evidence for an outburst, the former being simultaneous with an X-ray flare. We search for changes in the power spectra over the outburst duration and compare them with outbursts seen in other Be systems.
Mammalian RNase H1 directs RNA primer formation for mtDNA replication initiation and is also necessary for mtDNA replication completion
Authors: Misic Jelena , Milenkovic Dusanka , Al-Behadili Ali , Xie Xie , Jiang Min , Jiang Shan , Filograna Roberta , Koolmeister Camilla , Siira Stefan J , Jenninger Louise , Filipovska Aleksandra , Clausen Anders R , Caporali Leonardo , Valentino Maria Lucia , La Morgia Chiara , Carelli Valerio , Nicholls Thomas J , Wredenberg Anna , Falkenberg Maria , Larsson Nils-Göran
Published: August 2022

The in vivo role for RNase H1 in mammalian mitochondria has been much debated. Loss of RNase H1 is embryonic lethal and to further study its role in mtDNA expression we characterized a conditional knockout of Rnaseh1 in mouse heart. We report that RNase H1 is essential for processing of RNA primers to allow site-specific initiation of mtDNA replication. Without RNase H1, the RNA:DNA hybrids at the replication origins are not processed and mtDNA replication is initiated at non-canonical sites and becomes impaired. Importantly, RNase H1 is also needed for replication completion and in its absence linear deleted mtDNA molecules extending between the two origins of mtDNA replication are formed accompanied by mtDNA depletion. The steady-state levels of mitochondrial transcripts follow the levels of mtDNA, and RNA processing is not altered in the absence of RNase H1. Finally, we report the first patient with a homozygous pathogenic mutation in the hybrid-binding domain of RNase H1 causing impaired mtDNA replication. In contrast to catalytically inactive variants of RNase H1, this mutant version has enhanced enzyme activity but shows impaired primer formation. This finding shows that the RNase H1 activity must be strictly controlled to allow proper regulation of mtDNA replication.
Resistance of mitochondrial DNA to cadmium and Aflatoxin B1 damage-induced germline mutation accumulation inC. elegans
Authors: Leuthner Tess C , Benzing Laura , Kohrn Brendan F , Bergemann Christina M , Hipp Michael J , Hershberger Kathleen A , Mello Danielle F , Sokolskyi Tymofii , Stevenson Kevin , Merutka Ilaria R , Seay Sarah A , Gregory Simon G , Kennedy Scott R , Meyer Joel N
Published: August 2022

Mitochondrial DNA (mtDNA) is prone to mutation in aging and over evolutionary time, yet the processes that regulate the accumulation of de novo mtDNA mutations and modulate mtDNA heteroplasmy are not fully elucidated. Mitochondria lack certain DNA repair processes, which could contribute to polymerase error-induced mutations and increase susceptibility to chemical-induced mtDNA mutagenesis. We conducted error-corrected, ultra-sensitive Duplex Sequencing to investigate the effects of two known nuclear genome mutagens, cadmium and Aflatoxin B1, on germline mtDNA mutagenesis in Caenorhabditis elegans. Detection of thousands of mtDNA mutations revealed pervasive heteroplasmy in C. elegans and that mtDNA mutagenesis is dominated by C:G → A:T mutations generally attributed to oxidative damage. However, there was no effect of either exposure on mtDNA mutation frequency, spectrum, or trinucleotide context signature despite a significant increase in nuclear mutation rate after aflatoxin B1 exposure. Mitophagy-deficient mutants pink-1 and dct-1 accumulated significantly higher levels of mtDNA damage compared to wild-type C. elegans after exposures. However, there were only small differences in mtDNA mutation frequency, spectrum, or trinucleotide context signature compared to wild-type after 3050 generations, across all treatments. These findings suggest mitochondria harbor additional previously uncharacterized mechanisms that regulate mtDNA mutational processes across generations.
SUMMER: a Mendelian randomization interactive server to systematically evaluate the causal effects of risk factors and circulating biomarkers on pan-cancer survival
Authors: Xin Junyi , Gu Dongying , Chen Silu , Ben Shuai , Li Huiqin , Zhang Zhengdong , Du Mulong , Wang Meilin
Published: August 2022

Genome-wide association studies (GWASs) underlying case-control design have uncovered hundreds of genetic loci involved in tumorigenesis and provided rich resources for identifying risk factors and biomarkers associated with cancer susceptibility. However, the application of GWAS in determining the genetic architecture of cancer survival remains unestablished. Here, we systematically evaluated genetic effects at the genome-wide level on cancer survival that included overall survival (OS) and cancer-specific survival (CSS), leveraging data deposited in the UK Biobank cohort of a total of 19 628 incident patients across 17 cancer types. Furthermore, we assessed the causal effects of risk factors and circulating biomarkers on cancer prognosis via a Mendelian randomization (MR) analytic framework, which integrated cancer survival GWAS dataset, along with phenome-wide association study (PheWAS) and blood genome-wide gene expression/DNA methylation quantitative trait loci (eQTL/meQTL) datasets. On average, more than 10 traits, 700 genes, and 4,500 CpG sites were prone to cancer prognosis. Finally, we developed a user-friendly online database, SUrvival related cancer Multi-omics database via MEndelian Randomization (SUMMER; http://njmu-edu.cn:3838/SUMMER/), to help users query, browse, and download cancer survival results. In conclusion, SUMMER provides an important resource to assist the research community in understanding the genetic mechanisms of cancer survival.
Differential dependencies of human RNA polymerase II promoters on TBP, TAF1, TFIIB and XPB
Authors: Santana Juan F , Collins Geoffrey S , Parida Mrutyunjaya , Luse Donal S , Price David H
Published: August 2022

The effects of rapid acute depletion of components of RNA polymerase II (Pol II) general transcription factors (GTFs) that are thought to be critical for formation of preinitiation complexes (PICs) and initiation in vitro were quantified in HAP1 cells using precision nuclear run-on sequencing (PRO-Seq). The average dependencies for each factor across >70 000 promoters varied widely even though levels of depletions were similar. Some of the effects could be attributed to the presence or absence of core promoter elements such as the upstream TBP-specificity motif or downstream G-rich sequences, but some dependencies anti-correlated with such sequences. While depletion of TBP had a large effect on most Pol III promoters only a small fraction of Pol II promoters were similarly affected. TFIIB depletion had the largest general effect on Pol II and also correlated with apparent termination defects downstream of genes. Our results demonstrate that promoter activity is combinatorially influenced by recruitment of TFIID and sequence-specific transcription factors. They also suggest that interaction of the preinitiation complex (PIC) with nucleosomes can affect activity and that recruitment of TFIID containing TBP only plays a positive role at a subset of promoters.
Urinary extracellular vesicles and tubular transport
Authors: Rudolphi Crissy F , Blijdorp Charles J , van Willigenburg Hester , Salih Mahdi , Hoorn Ewout J
Published: August 2022

Tubular transport is a key function of the kidney to maintain electrolyte and acid-base homeostasis. Urinary extracellular vesicles (uEVs) harbor water, electrolyte, and acid-base transporters expressed at the apical plasma membrane of tubular epithelial cells. Within the uEV proteome, the correlations between kidney and uEV protein abundances are strongest for tubular transporters. Therefore, uEVs offer a noninvasive approach to probing tubular transport in health and disease. Here, we review how kidney tubular physiology is reflected in uEVs and, conversely, how uEVs may modify tubular transport. Clinically, uEV tubular transporter profiling has been applied to rare diseases, such as inherited tubulopathies, but also to more common conditions, such as hypertension and kidney disease. Although uEVs hold the promise to advance the diagnosis of kidney disease to the molecular level, several biological and technical complexities must still be addressed. The future will tell whether uEV analysis will mainly be a powerful tool to study tubular physiology in humans or whether it will move forward to become a diagnostic bedside test.
#Curbsiding: Potential Value and Patient Confidentiality Implications of Infectious Disease Clinician Peer Consultations via Social Media
Authors: Boyland Ryan , Marcelin Jasmine R , Cortés-Penfield Nicolás
Published: August 2022

Background

Infectious Disease (ID) clinician’s social media use for peer consultation is unstudied.

Methods

We reviewed ID peer consultation via Twitter over a 6-week period.

Results

We found this practice frequently solicited meaningful replies, but we identified potential for confidentiality breaches.

Conclusions

We offer recommendations for responsible discussion of clinical scenarios via social media.
Phloem Unloading in Developing Rice Caryopses and its Contribution to Non-Structural Carbohydrate Translocation from Stems and Grain Yield Formation
Authors: Li Guohui , Cui Kehui , Hu Qiuqian , Wang Wencheng , Pan Junfeng , Zhang Guo , Shi Yange , Nie Lixiao , Huang Jianliang , Peng Shaobing
Published: August 2022

Phloem unloading plays an important role in photoassimilate partitioning and grain yield improvements in cereal crops. The phloem unloading strategy and its effects on photoassimilate translocation and yield formation remain unclear in rice. In this study, plasmodesmata were observed at the interface between the sieve elements (SEs) and companion cells (CCs), and between the SE–CC complex and surrounding parenchyma cells (PCs) in phloem of the dorsal vascular bundle in developing caryopses. Carboxyfluorescein (CF) signal was detected in the phloem of caryopses, which showed that CF was unloaded into caryopses. These results indicated that the SE–CC complex was symplasmically connected with adjacent PCs by plasmodesmata. Gene expression for sucrose transporter (SUT) and cell wall invertase (CWI), and OsSUT1 and OsCIN1 proteins were detected in developing caryopses, indicating that rice plants might actively unload sucrose into caryopses by the apoplasmic pathway. Among three rice recombinant inbred lines, R201 exhibited lower plasmodesmal densities at the boundaries between cell types (SE–CC, SE–PC and CC–PC) in developing caryopses than R91 and R156. R201 also had lower expression of SUT and CWI genes and lower protein levels of OsSUT1 and OsCIN1, as well as CWI activity, than R91 and R156. These data agreed with stem non-structural carbohydrate (NSC) translocation and grain yields for the three lines. The nitrogen application rate had no significant effect on plasmodesmal densities at the interfaces between different cells types, and did not affect CF unloading in the phloem of developing caryopses. Low nitrogen treatment enhanced expression levels of OsSUT and OsCIN genes in the three lines. These results suggested that nitrogen application had no substantial effect on symplasmic unloading but affected apoplasmic unloading. Therefore, we concluded that poor symplasmic and apoplasmic unloading in developing caryopses might result in low stem NSC translocation and poor grain yield formation of R201.
Ascorbate peroxidase postcold regulation of chloroplast NADPH dehydrogenase activity controls cold memory
Authors: Seiml-Buchinger Victoria , Reifschneider Elena , Bittner Andras , Baier Margarete
Published: August 2022

Exposure of Arabidopsis (Arabidopsis thaliana) to 4°C imprints a cold memory that modulates gene expression in response to a second (triggering) stress stimulus applied several days later. Comparison of plastid transcriptomes of cold-primed and control plants directly before they were exposed to the triggering stimulus showed downregulation of several subunits of chloroplast NADPH dehydrogenase (NDH) and regulatory subunits of ATP synthase. NDH is, like proton gradient 5 (PGR5)–PGR5-like1 (PGRL1), a thylakoid-embedded, ferredoxin-dependent plastoquinone reductase that protects photosystem I and stabilizes ATP synthesis by cyclic electron transport (CET). Like PGRL1A and PGRL1B transcript levels, ndhA and ndhD transcript levels decreased during the 24-h long priming cold treatment. PGRL1 transcript levels were quickly reset in the postcold phase, but expression of ndhA remained low. The transcript abundances of other ndh genes decreased within the next days. Comparison of thylakoid-bound ascorbate peroxidase (tAPX)-free and transiently tAPX-overexpressing or tAPX-downregulating Arabidopsis lines demonstrated that ndh expression is suppressed by postcold induction of tAPX. Four days after cold priming, when tAPX protein accumulation was maximal, NDH activity was almost fully lost. Lack of the NdhH-folding chaperonin Crr27 (Cpn60β4), but not lack of the NDH activity modulating subunits NdhM, NdhO, or photosynthetic NDH subcomplex B2 (PnsB2), strengthened priming regulation of zinc finger of A. thaliana 10, which is a nuclear-localized target gene of the tAPX-dependent cold-priming pathway. We conclude that cold-priming modifies chloroplast-to-nucleus stress signaling by tAPX-mediated suppression of NDH-dependent CET and that plastid-encoded NdhH, which controls subcomplex A assembly, is of special importance for memory stabilization.
Considerations for Lumbar Medial Branch Nerve Radiofrequency at Spinal Motion Segments Adjacent to a Fusion Construct
Authors: Turtle Joel , Miller Scott , Yang Aaron , Hurley Robert W , Spina Nicholas , McCormick Zachary L
Published: August 2022

Instrumented lumbar spinal fusion is common and results in biomechanical changes at adjacent spinal segments that increase facet load bearing. This can cause facet-mediated pain at levels adjacent to the surgical construct. Medial branch nerve radiofrequency ablation (RFA) exists as a treatment for some cases. It is important to acknowledge that the approach and instrumentation used during some specific lumbar fusion approaches will disrupt the medial branch nerve(s). Thus, the proceduralist must consider the fusion approach when determining which medial branch nerves are necessary to anesthetize for diagnosis and then to potentially target with RFA. This article discusses the relevant technical considerations for preparing for RFA to denervate lumbosacral facet joints adjacent to fusion constructs.
C25-modified rifamycin derivatives with improved activity against Mycobacterium abscessus
Authors: Paulowski Laura , Beckham Katherine S H , Johansen Matt D , Berneking Laura , Van Nhi , Degefu Yonatan , Staack Sonja , Sotomayor Flor Vasquez , Asar Lucia , Rohde Holger , Aldridge Bree B , Aepfelbacher Martin , Parret Annabel , Wilmanns Matthias , Kremer Laurent , Combrink Keith , Maurer Florian P
Published: August 2022

Infections caused by Mycobacterium abscessus are difficult to treat due to its intrinsic resistance to most antibiotics. Formation of biofilms and the capacity of M. abscessus to survive inside host phagocytes further complicate eradication. Herein, we explored whether addition of a carbamate-linked group at the C25 position of rifamycin SV blocks enzymatic inactivation by ArrMab, an ADP-ribosyltransferase conferring resistance to rifampicin (RMP). Unlike RMP, 5j, a benzyl piperidine rifamycin derivative with a morpholino substituted C3 position and a naphthoquinone core, is not modified by purified ArrMab. Additionally, we show that the ArrMab D82 residue is essential for catalytic activity. Thermal profiling of ArrMab in the presence of 5j, RMP, or rifabutin shows that 5j does not bind to ArrMab. We found that the activity of 5j is comparable to amikacin against M. abscessus planktonic cultures and pellicles. Critically, 5j also exerts potent antimicrobial activity against M. abscessus in human macrophages and shows synergistic activity with amikacin and azithromycin.
Low-dose rituximab is efficacious in refractory idiopathic inflammatory myopathies
Authors: Janardana Ramya , Amin S N , Rajasekhar Liza , Pinto Benzeeta , Kodishala Chanakya , Selvam Sumithra , Shobha Vineeta
Published: August 2022

Objectives

Rituximab (RTX) use early in the course of refractory idiopathic inflammatory myopathy (IIM) is not well studied. This study sought to determine the short-term efficacy of RTX in a registry-based cohort of refractory IIM.

Methods

Registry-based observational data about IIM patients receiving RTX between 2018 and 2021 were included. Total improvement score was calculated from the core set measures as per International Myositis Assessment and Clinical Studies group (IMACS) at baseline, 6 months and 12 months of follow-up.

Results

Forty-two patients (F:M, 29:13), with a mean (s.d.) age of 39.5 (11.5) years were studied. Majority of patients received RTX for refractory myositis, after a median (interquartile range) duration of 8 (4,18) months. Twenty-eight received RTX at a dosage of 1 g × two doses, while 14 received 500 mg × two doses with an interval of 15 days. At 6 months and 12 months post-RTX, the improvement was recorded in manual muscle testing (MMT-8) scores, physician global assessment (PGA), patient global assessment (PtGA) and median steroid dosage as compared with the baseline (P < 0.01 for all). A mean (s.d.) improvement of 44.5 (16) and 48.7 (19.2) in total improvement score was recorded at 6 and 12 months, respectively. The change in MMT-8, PGA and PtGA scores from baseline between the two dosage regimens of RTX were comparable at 6 and 12 months. Severe lower respiratory tract infections requiring hospitalization occurred in three patients of the cohort.

Conclusion

RTX improved IMACS core set measures and had steroid sparing efficacy at 6 and 12 months in patients with IIM in this registry-based study. Rituximab as an induction regimen of two doses of 500 mg can be as efficacious as 1 g at 6 months and 12 months of follow-up.
Hepatic circadian and differentiation factors control liver susceptibility for fatty liver disease and tumorigenesis
Authors: Fekry Baharan , Ribas‐Latre Aleix , Drunen Rachel Van , Santos Rafael Bravo , Shivshankar Samay , Dai Yulin , Zhao Zhongming , Yoo Seung‐hee , Chen Zheng , Sun Kai , Sladek Frances M. , Younes Mamoun , Eckel‐Mahan Kristin
Published: August 2022

Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths, and the most common primary liver malignancy to present in the clinic. With the exception of liver transplant, treatment options for advanced HCC are limited, but improved tumor stratification could open the door to new treatment options. Previously, we demonstrated that the circadian regulator Aryl Hydrocarbon‐Like Receptor Like 1 (ARNTL, or Bmal1) and the liver‐enriched nuclear factor 4 alpha (HNF4α) are robustly co‐expressed in healthy liver but incompatible in the context of HCC. Faulty circadian expression of HNF4α– either by isoform switching, or loss of expression‐ results in an increased risk for HCC, while BMAL1 gain‐of‐function in HNF4α‐positive HCC results in apoptosis and tumor regression. We hypothesize that the transcriptional programs of HNF4α and BMAL1 are antagonistic in liver disease and HCC. Here, we study this antagonism by generating a mouse model with inducible loss of hepatic HNF4α and BMAL1 expression. The results reveal that simultaneous loss of HNF4α and BMAL1 is protective against fatty liver and HCC in carcinogen‐induced liver injury and in the “STAM” model of liver disease. Furthermore, our results suggest that targeting Bmal1 expression in the absence of HNF4α inhibits HCC growth and progression. Specifically, pharmacological suppression of Bmal1 in HNF4α‐deficient, BMAL1‐positive HCC with REV‐ERB agonist SR9009 impairs tumor cell proliferation and migration in a REV‐ERB‐dependent manner, while having no effect on healthy hepatocytes. Collectively, our results suggest that stratification of HCC based on HNF4α and BMAL1 expression may provide a new perspective on HCC properties and potential targeted therapeutics.
An Exploration of Resiliency Among Nurse Educators During the COVID-19 Pandemic
Authors: Nurse-Clarke Natasha , Sockol Laura E.
Published: August 2022

AIM

The purpose of this study was to explore resilience among nursing faculty during the COVID-19 pandemic and to examine associations or differences that may exist among variables and between groups.

BACKGROUND

Nurse educators’ resilience has been identified as an important characteristic because of the challenges involved in nursing education. It is important to explore resilience among nurse educators to determine which factors promote or inhibit this important characteristic.

METHOD

This correlational research study used an online survey to explore factors related to resilience among nurse faculty during the COVID-19 pandemic. Correlational analyses were used to determine the relationship between various resilience constructs and select demographic variables.

RESULTS

Findings indicated that higher levels of resilience were associated with age (ρ = .21, p < .001), experience teaching online (r = .22, p < .001), and professional development related to online teaching (M = 80.7, SD = 11.0), t(276) = 2.41, p = .017.

CONCLUSION

Resilience and related characteristics have the potential to assist nurse educators in adapting successfully to stressful circumstances. It is crucial that schools of nursing develop programs to enhance or develop resilience among nurse educators. Support and training in the area of online education are also of paramount importance.
Transition to Practice: The Use of Virtual Clinical Replacement During the COVID-19 Pandemic and Its Impact on New Graduate Nurse Readiness
Authors: Ulmen Brenda F. , Witte Cynthia E. , Speckhard Samuel T. , Fenske Cynthia L.
Published: August 2022

AIM

This study investigated graduate nurse readiness for practice after receiving virtual clinical replacement experiences during the COVID-19 pandemic.

BACKGROUND

The pandemic led to the closure of clinical sites for many undergraduate nursing students. Nurse educators replaced the hospital setting with virtual clinical replacement experiences, potentially affecting readiness for practice in graduate nurses.

METHOD

The Casey-Fink Graduate Nurse Experience Survey was used to collect data in the areas of demographics, comfort level with skills, work environment stress, job satisfaction, role transition, and the impact of the virtual clinical experience on transition to practice. Descriptive statistics and independent t-tests were used for analysis.

RESULTS

The virtual clinical replacement experience was statistically significant with greater confidence in providing for patient safety, stronger professional communication/leadership skills, and recognized support in the workplace.

CONCLUSION

The use of virtual clinical replacement experiences had a positive impact on new graduate nurses’ transition to practice.
Impact of Patient-specific Factors and Spinopelvic Alignment on the Development of Adjacent Segment Degeneration After Short-segment Lumbar Fusion
Authors: Kiss Laszlo , Szoverfi Zsolt , Bereczki Ferenc , Eltes Peter Endre , Szollosi Balazs , Szita Julia , Hoffer Zoltan , Lazary Aron
Published: August 2022

Study Design:

Prospective cross-sectional cohort study.

Objectives:

The main purpose of this study was to evaluate the association between demographical, surgery-related and morphologic parameters, and the development or progress of adjacent segment degeneration (ASD) after short-segment lumbar fusions.

Summary of Background Data:

ASD is a major long-term complication after lumbar fusions. Possible risk factors are related to the patients’ demographics, spinopelvic anatomy, or preoperative lumbar intervertebral disk conditions, but the role of these parameters is still not clear.

Methods:

A prospective cross-sectional study of 100 patients who underwent 1- or 2-level open lumbar transforaminal interbody fusions due to a lumbar degenerative pathology was conducted. Demographical, radiologic findings, and magnetic resonance imaging features were analyzed to identify factors associated with ASD in 5-year follow-up.

Results:

ASD patients showed higher level of pain (P=0.004) and disability (P=0.020) at follow-up. In univariate analysis, older age (P=0.007), upper-level lumbar fusion (P=0.007), lower L4-S1 lordosis (P=0.039), pelvic incidence-lumbar lordosis mismatch (P=0.021), Pfirrmann grade III or higher disk degeneration (P=0.002), and the presence of disk bulge/protrusion (P=0.007) were associated with ASD. In multivariate analysis, the presence of major degenerative sign (disk degeneration and/or disk bulge) was the significant predictor for developing ASD (odds ratio: 3.85, P=0.006).

Conclusion:

By examining the role of different patient- and procedure-specific factors, we found that preoperative major degenerative signs at the adjacent segment increase the risk of ASD causing significantly worse outcome after short-segment lumbar fusion. On the basis of our results, adjacent disk conditions should be considered carefully during surgical planning.
Reactive oxygen species–dependent upregulation of death receptor, tumor necrosis factor receptor 1, is responsible for theophylline-mediated cytotoxicity in MDA-MB-231 breast cancer cells
Authors: Tapadar Poulami , Pal Ambika , Ghosal Nirajan , Dutta Siddhartha , Pal Ranjana
Published: August 2022

Theophylline, a methylxanthine drug, has been used as a therapy for respiratory diseases. Recently, it has also been shown to have a potential in treating different cancers. Also, it has shown promising results in clinical trials for AML in combination therapy. Subsequently, studies have shown theophylline to kill breast cancer cells but not normal breast cells. Therefore, in this study, we have explored the molecular mechanism underlying the cytotoxic effect of theophylline on breast cancer cells. Theophylline-treated cancer cells were analyzed for the transcript and protein expression of candidate apoptotic genes such as TNFR1, caspase-8, -9, -3 using qPCR and immunoblotting, respectively. Cell viability and apoptosis was measured in the presence or absence of TNFR1 inhibitor, R7050, using AO/EtBr staining and MTT assay, respectively. Similarly, oxidative stress was studied by analyzing ROS in the presence or absence of ROS inhibitor, NAC, using DCFDA assay. Theophylline caused reduced cell viability in cancer but not normal cells. Theophylline-treated breast cancer cells showed increased expression of death receptor, TNFR1, along with elevated levels of active caspase-8, -9 and -3. Inhibition of TNFR1 reduced caspase-dependent apoptosis even in the presence of theophylline. Theophylline further caused increased ROS generation, inhibition of which resulted in reduced TNFR1-mediated apoptosis. Theophylline also increased cathepsin activity, which was reduced on exposure of cells to TNFR1 inhibitor, R7050. We conclude that ROS-mediated activation of TNFR1 is responsible for caspase-3 and cathepsin-dependent cell death in breast cancer cells on exposure to theophylline.
Epidermal growth factor receptor mutation p.A864V in small cell lung cancer and lung squamous cell carcinoma: a case report and review of literature
Authors: Deng Wusheng , Chen Gang , Xiong Dandan , He Rongquan , Wang Ke , Lu Huasong , Kong Jinliang
Published: August 2022

Mutations in the epidermal growth factor receptor (EGFR) have been identified in 10–20% of nonsmall cell lung cancer (NSCLC), specifically lung adenocarcinomas. However, these mutations have rarely been reported in small cell lung cancer (SCLC) and lung squamous cell carcinoma (LUSC). Treatment for SCLC and LUSC patients has not yet been established. We present a rare case of p.A864V mutation in Exon 21 of EGFR gene in a patient with both SCLC and LUSC, which is the first case of such mutation type in lung cancer in the world. The patient was a 55-year-old female nonsmoker with stage IV SCLC and LUSC, gene sequencing revealed EGFR gene mutation, she refused EGFR tyrosine kinase inhibitors (TKIs) targeted therapy and received conservative treatment, which led to disease progression. In conclusion, clinicians should be aware of the possibility of the rare EGFR mutations. Platinum-based chemotherapy can be treated for SCLC and LUSC patients.
Immune checkpoint inhibitor in a case with primary urethral adenocarcinoma with lung metastasis
Authors: Ma Ji , Liang Xiuping , Miao Jidong , Li Jiawei , Wang Xin
Published: August 2022

Primary urethral adenocarcinoma is extremely rare, and the clinical experience in optimizing the management is limited. The efficacy of immune checkpoint inhibitors for these patients is not clear. Here, we describe a 52-year-old patient with primary urethral adenocarcinoma accompanied by inguinal lymph nodes and lung metastasis with progressive disease after radiotherapy and multiline chemotherapy. The expression of programmed cell death ligand-1 (PD-L1) was positive. Hence, this patient was treated with tislelizumab, an immune checkpoint inhibitor. The disease is well controlled and the overall survival time is 5 years. Moreover, the patient tolerated the treatment well. To our knowledge, this is the first reported case in which immunotherapy was used for primary urethral adenocarcinoma. The immune checkpoint inhibitors may be a novel option for the treatment of these patients.
Chronic hyperglycemia based on diabetes is independently associated with decreased survival in patients with advanced cancer treated with immune checkpoint inhibitors
Authors: Yekedüz Emre , Köksoy Elif Berna , Yazgan Sati Coşkun , Karataş Göktürk , Şenler Filiz Çay , Utkan Güngör , Akbulut Hakan , Demirkazik Ahmet , Ürün Yüksel
Published: August 2022

Immune checkpoint inhibitors (ICIs) have started a new era in treating patients with cancer. The effect of comorbidities and concomitant drug use on ICIs have become of interest in those patients. Data about the impact of hyperglycemia on response to ICIs in cancer patients are limited. All advanced-stage cancer patients treated with ICIs in Ankara University Medical Oncology Department were retrospectively evaluated. Patients treated in expanded access programs or clinical trials were excluded from the study. A total of 137 patients were included in this study. The most common primary tumor type was malign melanoma (32.8%) and nivolumab (62.3%) was the most common used ICI. More than half of patients (57.7%) had lung metastasis at the initiation of ICIs. Thirty-five patients (25.5%) had diabetes before initiating ICIs. Median baseline fasting glucose level was higher in patients with diabetes than those without diabetes (117 mg/dl vs. 99 mg/dl, P = 0.002). In all patients, median overall survival and progression-free survival were 11.3 [95% confidence interval (CI), 8.1–14.4) and 5.9 (95% CI, 3.6–8.3) months, respectively. In multivariate analysis, diabetes was found to increase risk of death [hazard ratio (HR), 2.09; 95% CI, 1.27–3.43, P = 0.004) and disease progression (HR, 2.01, 95% CI, 1.29–3.09, P = 0.002). Hyperglycemia might decrease response to ICIs in patients with advanced cancer. This research area is still an unmet need in the immunotherapy era. Prospective studies are needed to elucidate the effect of hyperglycemia on the response to ICIs.
Identification of exosomal circRNA CD226 as a potent driver of nonsmall cell lung cancer through miR-1224-3p/high mobility group AT-hook 2 axis
Authors: Peng Lihong , Cao Yunpeng , Hu Chao
Published: August 2022

Circular RNAs (circRNAs) are crucial for the pathogenesis of nonsmall lung cancer (NSCLC). Here, we set out to unravel the precise function of circRNA CD226 (circCD226) in NSCLC pathogenesis. The exosomes from serum specimens were observed by transmission electron microscopy. CircCD226, miR-1224-3p and high mobility group AT-hook 2 (HMGA2) were quantified by qRT-PCR, western blot and immunohistochemistry. Actinomycin D and Ribonuclease (RNase) R treatments and subcellular localization assay were used for circCD226 characterization. Cell viability, proliferation, migration, invasion and sphere formation abilities were gauged by CCK-8, EDU, wound-healing, transwell and sphere formation assays, respectively. Directed relationships among circCD226, miR-1224-3p and HMGA2 were examined by RNA pull-down, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The abundance of circCD226 was elevated in serum exosomes, tissues and cells of NSCLC. NSCLC serum exosomes enhanced NSCLC cell proliferation, migration, invasion and stemness. Loss of circCD226 impeded cell proliferation, migration, invasion and stemness in vitro, as well as tumor growth in vivo. Mechanistically, circCD226 sponged miR-1224-3p, and miR-1224-3p targeted HMGA2. CircCD226 involved the posttranscriptional regulation of HMGA2 through miR-1224-3p. Moreover, the miR-1224-3p/HMGA2 axis was identified as a functionally downstream effector of circCD226 in regulating NSCLC cell behaviors. Our study identifies circCD226 as a potential driver in NSCLC development depending on the regulation of miR-1224-3p/HMGA2 axis.
Savolitinib monotherapy exerted significant benefit in a non-small cell lung cancer patient with osimertinib resistance harboring primary EGFR L858R mutation and MET amplification: a case report
Authors: Ma Pei , Huang Ruohan , Gu Yunru , Fang Yuan , Wu Xi , Chen Dong-sheng , Zhang Han-wu , Gao Wen , Shu Yongqian
Published: August 2022

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved response in all stages of patients with EGFR positive mutations in nonsmall cell lung cancer. However, the primary resistance mechanism of EGFR-TKIs has not been thoroughly revealed. Here, we described a case of a 64-year-old male with lung adenocarcinoma presented primary resistance on osimertinib combined with bevacizumab and platinum-based chemotherapy, next-generation sequencing revealed EGFR exon 21 L858R mutation and MET gene amplification. Afterward, savolitinib monotherapy was started until now, and the treatment was temporarily successful, the last follow-up clinical evaluation was near complete response, the progression-free survival has over 7 months. Our case highlights that EGFR-TKIs may be not the optimal choice for lung adenocarcinoma with primary EGFR-sensitive mutation with MET amplification simultaneously, whereas MET inhibitor alone may be an effective treatment option. In clinical practice, we should fully consider the possibility of primary resistance in EGFR-TKIs administration.
A case report on disseminated tuberculosis in the setting of coronavirus disease 2019: cause or consequence?
Authors: Khataniar Himsikhar , Sunil Diya , AV Lalitha
Published: August 2022

Tuberculosis (TB) is a deadly infection that can lead to disseminated disease in children <15years of age exhibiting risk factors such as low host immunity, concurrent infection(s), and/or malnutrition. A case involving a 14-year-old boy diagnosed with disseminated tuberculosis is reported. On investigation, the patient was positive for coronavirus disease 2019 (COVID-19) antibodies, GeneXpert (Cepheid, Sunnyvale, CA) positive for TB with multisystem involvement, lymphopenia, and highly elevated inflammatory markers, indicating multisystem inflammatory syndrome in children (MIS-C) and disseminated TB. The patient was started on antitubercular treatment (ATT), steroids, and supportive treatment. His condition improved over the ensuing few days, and he was discharged with ATT and antiepileptics. Although a few studies involving adults have established a connection between the progression of TB and COVID-19, this case report establishes a similar clinical picture in a child, which has not yet been reported.
Complementary and Integrative Health Practices in a Brazilian Freestanding Birth Center
Authors: Leister Nathalie , Teixeira Thaís Trevisan , Mascarenhas Victor Hugo Alves , Gouveia Luciana Magnoni Reberte , Caroci-Becker Adriana , Riesco Maria Luiza
Published: August 2022

The study aimed to analyze the use of complementary and integrative health practices (CIHPs) during labor and birth in a freestanding birth center. A total of 28 different CIHPs were applied with or used by laboring women. The most adopted CIHPs were mind-body practices (99.9%) and natural products (35.5%), mostly used by primiparous women (P <.05). Adopting CIHPs can increase care quality, increase positive experiences during childbirth, and promote evidence-based choices.
Abdominoplasty as an acute postoperative pain model: insights from 8 years of clinical trials
Authors: Singla Neil , Rogier Timothy
Published: August 2022

To have a complete understanding of an experimental analgesic's efficacy in treating acute postoperative pain, it is necessary to understand its effect on both hard-tissue pain and soft-tissue pain. For this reason, regulatory bodies including the U.S. Food and Drug Administration and European EMA typically require drug developers to demonstrate efficacy in both hard-tissue and soft-tissue pain to grant a broad approval for an analgesic in acute postoperative pain. Hard-tissue models such as bunionectomy and molar extraction are well-validated and efficient with long histories in clinical trials, but until recently, a similarly well-standardized and fast-enrolling soft-tissue model was not available. Abdominoplasty was developed as an acute postoperative pain model and introduced to the clinical trial marketplace in 2014 to address the need for a viable soft-tissue model. Since then, at least 13 industry-sponsored studies, including multiple pivotal trials, have been conducted, providing a data set that can be used to interrogate the model's strengths and weaknesses. The authors outline the development history of abdominoplasty, discuss key clinical and design characteristics of the model, and review public data from abdominoplasty acute pain studies available to date. The data suggest that abdominoplasty is a well-validated soft-tissue surgical model that provides high-quality experimental outputs, enabling the efficacy of investigational analgesics in soft-tissue pain to be understood successfully.
No long-term effects after a 3-week open-label placebo treatment for chronic low back pain: a 3-year follow-up of a randomized controlled trial
Authors: Kleine-Borgmann Julian , Dietz Tim-Niklas , Schmidt Katharina , Bingel Ulrike
Published: August 2022

Chronic low back pain is prevalent, highly disabling, and a relevant socioeconomic health concern. Although allocated to placebo groups, patients in randomized controlled trials show significant pain relief, pointing to the relevance of placebo effects. Overcoming ethical and legal concerns related to deceptive placebos, recent studies have demonstrated the efficacy of short-term treatments for chronic low back pain with open-label (ie, nondeceptive) placebos. However, data on long-term efficacy of open-label placebos are sparse. Here, we report a 3-year follow-up of our previously published randomized controlled trial demonstrating pain reduction, improvement in disability, and depressive symptoms after a 3-week treatment with open-label placebos. Including records from 89 previously enrolled patients, we investigated changes between the groups with and without previous open-label placebo treatment in pain intensity (primary outcome), disability and mood (secondary outcomes), biopsychosocial factors and lifestyle (exploratory outcomes) from parent baseline to follow-up. Over the 3-year period, there were no differences in any outcome between groups with and without open-label placebo treatment. Therefore, our follow-up data do not support the previously suggested assumption that a 3-week open-label placebo treatment has long-term effects. This study was preregistered on April 14, 2020, in the German Clinical Trials Register (registration number DRKS00021405).
Association between personality traits and placebo effects: a preregistered systematic review and meta-analysis
Authors: Kang Heemin , Miksche Miriam Sophie , Ellingsen Dan-Mikael
Published: August 2022

Placebo effects are ubiquitous yet highly variable between individuals and therefore strongly affect clinical trial outcomes such as pain relief. It is unclear whether dispositional psychological traits influence responsiveness to placebo. This preregistered meta-analysis and systematic review synthesized the literature investigating the association between personality traits and placebo effects. Based on 21 studies with 798 participants, we performed formal meta-analyses for 10 different personality traits, including behavioral inhibition, fun seeking, goal-drive persistence, reward responsiveness, empathic concern, empathic fantasy, perspective-taking, personal distress, optimism, and anxiety. We did not find evidence of associations between any of these traits and magnitude of placebo effects, which was supported by equivalence tests. Furthermore, we did not find evidence for moderating factors such as placebo manipulation type (conditioning or nonconditioning) or condition (pain or nonpain). These findings challenge the notion that personality influences responsiveness to placebos and contradict its utility for identifying placebo “responders” and “nonresponders.”
The characteristics and prognostic significance of the SET-CAN/NUP214 fusion gene in hematological malignancies: A systematic review
Authors: Wang Jing , Zhan Qian-ru , Lu Xiao-xuan , Zhang Li-jun , Wang Xiao-xue , Zhang He-yang
Published: August 2022

Background:

The SET-CAN/NUP214 fusion gene resulting from chromosomal del(9)(q34.11q34.13) or t(9;9) (q34;q34) has been found in T-cell acute lymphoblastic leukemia (T-ALL), B-cell acute lymphoblastic leukemia (B-ALL), acute myeloid leukemia (AML) and myeloid sarcoma (MS). Furthermore, the SET-CAN/NUP214 fusion gene has been found in the T-ALL cell line LOUCY and the AML line MEGAL. The common features of these cases are insensitivity to chemotherapy and poor prognosis. We reviewed the characteristics and prognostic significance of the SET-CAN/NUP214 fusion gene in hematological malignancies.

Methods:

This systematic literature search was conducted using the PubMed, Web of Science, Embase, and Cochrane Library databases. With the inclusion and exclusion criteria, we summarized all of the papers and performed a statistical analyses.

Results:

In general, the SET-CAN/NUP214 fusion gene is very rare in adult acute leukemia, more frequently found in T-ALL than in other types of leukemia, and more often in males. Flow cytometry data indicated that the markers CD34, CD33, CD13, and CD7 were common in SET-CAN/NUP214 positive acute leukemia, including ALL. Fluorescence in situ hybridization and arrays are important methods for detecting the fusion gene in newly diagnosed patients and can detect chromosomal del(9)(q34) will be detected. The chromosomal karyotype may be normal or complex, and, in terms of survival analysis, transplantation results in a better prognosis than chemotherapy alone.

Conclusions and implications of key findings:

The presence of SET-CAN/NUP214 fusion gene may be a Minimal Residual Disease of early recurrence, and it might be a poor indicator of outcome.

Limitations:

The mechanism, clinical characteristics, therapy and prognosis of the SET-CAN/NUP214 fusion gene in hematological malignancies require further research.
Prognostic significance of long noncoding RNA HOTAIR in hepatocellular carcinoma: A protocol for systematic review and meta-analysis
Authors: Feng Lei , Liu Wenqing , Lv Yunhuo , Qiao Baojun
Published: August 2022

Background:

Homeobox transcript antisense intergenic RNA (HOTAIR), a long noncoding RNA, has been reported to associate with the prognosis of patients with hepatocellular carcinoma (HCC) in several studies, however, the definite conclusion has not been obtained for conflicting results across different studies. The aim of this study is to determine the association of HOTAIR expression with overall survival, progression-free survival, and clinical features in HCC.

Methods:

PubMed, Cochrane Library, and Embase will be comprehensively searched to seek the relevant studies. The studies meeting the inclusion criteria will be included into this systematic review and meta-analysis. A combination of hazard ratio and 95% confidence interval is used to estimate the impact of HOTAIR expression on the overall survival and progression-free survival in HCC. The relationship between HOTAIR expression and clinical features of HCC is evaluated using the odds ratio and 95% confidence interval. The study quality is evaluated with the “risk of bias assessment” tool in Cochrane System Assessment Manual or Newcastle-Ottawa Scale. The subgroup analysis, publication bias, and sensitivity analysis are performed.

Results:

This study provides a strict and classic protocol for systematic review and meta-analysis to determine the prognostic significance of HOTAIR expression in HCC. The findings of this systematic review and meta-analysis may provide a novel diagnostic indicator and potential therapeutic target of HCC.

Ethics and dissemination:

This study is only a protocol for systematic review and meta-analysis, and all data used in this study is acquired through published studies. Therefore, the ethical review is not needed for this study.

Registration number:

INPLASY202230050.