bluuebunny/crossref_metadata_2025_split huggingface dataset:
The WID‐qEC test: Performance in a hospital‐based cohort and feasibility to detect endometrial and cervical cancers
Authors: Schreiberhuber Lena , Herzog Chiara , Vavourakis Charlotte D. , Redl Elisa , Kastner Christine , Jones Allison , Evans Iona , Zikan Michal , Cibula David , Widschwendter Peter , Pfau Karin , Math Barbara , Seewald Martin , Amory Sylvain , Obrist Peter , Widschwendter Martin 
Published: September 2022

AbstractThe majority of endometrial and cervical cancers present with abnormal vaginal bleeding but only a small proportion of women suffering from vaginal bleeding actually have such a cancer. A simple, operator‐independent and accurate test to correctly identify women presenting with abnormal bleeding as a consequence of endometrial or cervical cancer is urgently required. We have recently developed and validated the WID‐qEC test, which assesses DNA methylation of ZSCAN12 and GYPC via real‐time PCR, to triage women with symptoms suggestive of endometrial cancer using ThinPrep‐based liquid cytology samples. Here, we investigated whether the WID‐qEC test can additionally identify women with cervical cancer. Moreover, we evaluate the test's applicability in a SurePath‐based hospital‐cohort by comparing its ability to detect endometrial and cervical cancer to cytology. In a set of 23 cervical cancer cases and 28 matched controls the receiver operating characteristic (ROC) area under the curve (AUC) is 0.99 (95% confidence interval [CI]: 0.97‐1.00) with a sensitivity and specificity of 100% and 92.9%, respectively. Amongst the hospital‐cohort (n = 330), the ROC AUC is 0.99 (95% CI: 0.98‐1) with a sensitivity and specificity of 100% and 82.5% for the WID‐qEC test, respectively, and 33.3% and 96.9% for cytology (considering PAP IV/V as positive). Our data suggest that the WID‐qEC test detects both endometrial and cervical cancer with high accuracy.
A high‐throughput approach to predict A‐to‐I effects on RNA structure indicates a change of double‐stranded content in noncoding RNAs
Authors: Delli Ponti Riccardo , Broglia Laura , Vandelli Andrea , Armaos Alexandros , Burgas Marc Torrent , Sanchez de Groot Natalia , Tartaglia Gian Gaetano 
Published: September 2022

AbstractRNA molecules undergo a number of chemical modifications whose effects can alter their structure and molecular interactions. Previous studies have shown that RNA editing can impact the formation of ribonucleoprotein complexes and influence the assembly of membrane‐less organelles such as stress granules. For instance, N6‐methyladenosine (m6A) enhances SG formation and N1‐methyladenosine (m1A) prevents their transition to solid‐like aggregates. Yet, very little is known about adenosine to inosine (A‐to‐I) modification that is very abundant in human cells and not only impacts mRNAs but also noncoding RNAs. Here, we introduce the CROSSalive predictor of A‐to‐I effects on RNA structure based on high‐throughput in‐cell experiments. Our method shows an accuracy of 90% in predicting the single and double‐stranded content of transcripts and identifies a general enrichment of double‐stranded regions caused by A‐to‐I in long intergenic noncoding RNAs (lincRNAs). For the individual cases of NEAT1, NORAD, and XIST, we investigated the relationship between A‐to‐I editing and interactions with RNA‐binding proteins using available CLIP data and catRAPID predictions. We found that A‐to‐I editing is linked to the alteration of interaction sites with proteins involved in phase separation, which suggests that RNP assembly can be influenced by A‐to‐I. CROSSalive is available at http://service.tartaglialab.com/new_submission/crossalive.
Nonattendance in addiction mental health services: Patient and appointment factors
Authors: Blaauw Eric , Venema Simon D. , Muskee Liza 
Published: September 2022

AbstractThis study examined patient and appointment factors as predictors of nonattendance in addiction mental health services. Data were collected from the electronic files of 7,641 patients treated for a substance use disorder in outpatient clinics of an addiction mental health organization in the Netherlands. Negative binomial regression analyses revealed that cocaine use, poly substance use, limitations in interpersonal functioning, presence of anxiety disorder and cluster C personality disorder, age, level of education, source of income, and planning consistency were associated with nonattendance.
Lactational exposure to venlafaxine provokes late repercussions on reproductive parameters in male rat offspring
Authors: da Silva Moreira Suyane , de Matos Manoel Beatriz , Inácio João Pedro Gaspar , de Souza Carolina Gabrielli , Reis Ana Carolina Casali , Jorge Bárbara Campos , de Aquino Ariana Musa , Scarano Wellerson Rodrigo , Cardoso Claudia Andrea Lima , Arena Arielle Cristina 
Published: September 2022

AbstractExposure to selective serotonin reuptake inhibitors can affect hormone‐dependent processes, such as the brain sexual differentiation. Because the use of these antidepressants cause concern during lactation, we evaluated the possible effects of venlafaxine on lactational exposure and its late repercussions on reproductive parameters in male rats. Lactating rats were exposed to venlafaxine (3.85, 7.7, or 15.4 mg/kg/body weight; gavage), from lactational day 1 to 20. Venlafaxine and O‐desmethylvenlafaxine residues were found in all milk samples of dams treated, demonstrating the lactational transfer of this antidepressant to the offspring. Although the maternal behavior was normal, the dams presented an increase in urea and uric acid levels in the groups treated with 7.7 and 15.4, respectively, as well as a spleen weight increased in the 3.85 and 15.4 groups. The male offspring showed a decrease in play behavior parameters in the intermediate dose group. Sperm analysis indicated a reduction in sperm motility in all treated groups. The androgen receptor expression in the hypothalamus was decreased in the highest dose group, although the sexual behavior had not been affected. In conclusion, venlafaxine was transferred through breast milk and promoted changes in play behavior, sperm quality, and hypothalamic androgen receptor (AR) content, which may indicate an incomplete masculinization of the brain of male offspring.
Tri‐mode optical biopsy probe with fluorescence endomicroscopy, Raman spectroscopy, and time‐resolved fluorescence spectroscopy
Authors: Wood Harry Alexander Charles , Ehrlich Katjana , Yerolatsitis Stephanos , Kufcsák András , Quinn Tom Michael , Fernandes Susan , Norberg Dominic , Jenkins Nia Caitlin , Young Vikki , Young Irene , Hamilton Katie , Seth Sohan , Akram Ahsan , Thomson Robert Rodrick , Finlayson Keith , Dhaliwal Kevin , Stone James Morgan 
Published: September 2022

AbstractWe present an endoscopic probe that combines three distinct optical fibre technologies including: A high‐resolution imaging fibre for optical endomicroscopy, a multimode fibre for time‐resolved fluorescence spectroscopy, and a hollow‐core fibre with multimode signal collection cores for Raman spectroscopy. The three fibers are all enclosed within a 1.2 mm diameter clinical grade catheter with a 1.4 mm end cap. To demonstrate the probe's flexibility we provide data acquired with it in loops of radii down to 2 cm. We then use the probe in an anatomically accurate model of adult human airways, showing that it can be navigated to any part of the distal lung using a commercial bronchoscope. Finally, we present data acquired from fresh ex vivo human lung tissue. Our experiments show that this minimally invasive probe can deliver real‐time optical biopsies from within the distal lung ‐ simultaneously acquiring co‐located high‐resolution endomicroscopy and biochemical spectra.
CGRP induces myofibroblast differentiation and the production of extracellular matrix in MRC5s via autocrine and paracrine signalings
Authors: Kayalar Ozgecan , Oztay Fusun 
Published: September 2022

AbstractThere are contradictory views on which calcitonin gene‐related peptide (CGRP) causes pulmonary fibrosis. Fibrotic potency of CGRP was tested and compared to that of transforming growth factor‐β (TGF‐β). Myofibroblast differentiation, cell proliferation, and activations of TGF‐β and Wnt pathways were examined for 24, 48, and 72 h in A549 and MRC5 cell lines stimulated with CGRP and TGF‐β. CGRP‐induced cell proliferation in MRC5s early on while cell proliferation in A549 occurred progressively. CGRP promoted fibroblast‐myofibroblast differentiation by inducing the transcription of ACTA2, COL1A1, SMAD2/3, and SMAD4 genes, the production of collagen, fibronectin, α‐smooth muscle actin, and activation of TGF‐β signaling starting from 24 h. Additionally, TGF‐β signaling induced by CGRP decreased the DKK1 level and activated the Wnt signaling in MRC5s. After CGRP stimulation, Wnt7a levels were increased from 24 to 72 h, while Wnt5a levels were elevated at 72 h in MRC5s. CGRP did not induce epithelial–mesenchymal transition in A549s, unlike TGF‐β. A comparison of fibrotic potency of CGRP and TGF‐β showed that TGF‐β is a powerful profibrotic molecule and induces earlier myofibroblast differentiation. Even so, CGRP promotes myofibroblast differentiation and extracellular matrix production by inducing Smad‐dependent‐TGF‐β and Wnt signalings via autocrine and paracrine signalings in MRC5s.
PDE4 inhibitor eliminates breast cancer stem cells via noncanonical activation of mTOR
Authors: Mukherjee Pritha , Bagchi Arka , Banerjee Ananya , Roy Himansu , Bhattacharya Arijit , Biswas Arunima , Chatterji Urmi 
Published: September 2022

AbstractIneffective cancer treatment is implicated in metastasis, recurrence, resistance to chemotherapy and radiotherapy, and evasion of immune surveillance. All these failures occur due to the persistence of cancer stem cells (CSCs) even after rigorous therapy, thereby rendering them as essential targets for cancer management. Contrary to the quiescent nature of CSCs, a gene profiler array disclosed that phosphatidylinositol‐3‐kinase (PI3K), which is known to be crucial for cell proliferation, differentiation, and survival, was significantly upregulated in CSCs. Since PI3K is modulated by cyclic adenosine 3′,5′ monophosphate (cAMP), analyses of cAMP regulation revealed that breast CSCs expressed increased levels of phosphodiesterase 4 (PDE4) in contrast to normal stem cells. In accordance, the effects of rolipram, a PDE4 inhibitor, were evaluated on PI3K regulators and signaling. The efficacy of rolipram was compared with paclitaxel, an anticancer drug that is ineffective in obliterating breast CSCs. Analyses of downstream signaling components revealed a switch between cell survival and death, in response to rolipram, specifically of the CSCs. Rolipram‐mediated downregulation of PDE4A levels in breast CSCs led to an increase in cAMP levels and protein kinase A (PKA) expression. Subsequently, PKA‐mediated upregulation of phosphatase and tensin homolog antagonized the PI3K/AKT/mTOR pathway and led to cell cycle arrest. Interestingly, direct yet noncanonical activation of mTOR by PKA, circumventing the influence of PI3K and AKT, temporally shifted the fate of CSCs toward apoptosis. Rolipram in combination with paclitaxel indicated synergistic consequences, which effectively obliterated CSCs within a tumor, thereby suggesting combinatorial therapy as a sustainable and effective strategy to abrogate breast CSCs for better patient prognosis.
The reactivity of the trapping reaction of the benzene‐bridged boron/phosphorus‐based frustrated Lewis pair with difluorocarbene and its group 14 analogs: A theoretical investigation
Authors: Zhang Zheng‐Feng , Su Ming‐Der 
Published: September 2022

AbstractThe trapping reactions of carbene analogsG14F2(G14 = group 14 element) by the benzene‐bridgedB/P‐Reafrustrated Lewis pair (FLPs) molecule are studied using density functional theory (B3LYP‐D3(BJ)/def2‐TZVP). Our theoretical investigations predict that only theCF2intermediate rather than other heavy carbene analogs can be trapped by theB/P‐ReaFLP‐type molecule. Energy decomposition analysis‐natural orbitals for chemical valence (EDA‐NOCV) analyses indicate that the bonding nature of theG14F2catching reactions by theB/P‐ReaFLP‐type molecule is a donor–acceptor (singlet–singlet) interaction rather than an electron‐sharing (triplet–triplet) interaction. Moreover, EDA‐NOCV and frontier molecular orbital (FMO) theory findings strongly suggest that the lone pair (LP) (P) → vacant p–π‐orbital (G14F2) interaction rather than the empty σ‐orbital (B) ← sp2‐σ‐orbital (G14F2) interaction plays a predominant role in establishing its bonding condition during theG14F2trapping reaction with theB/P‐ReaFLP‐associated molecule. Our activation strain model findings reveal that the atomic radius of the G14 element ofG14F2plays a key role in determining the activation barrier of theG14F2trapping reactions by the benzene‐bridgedB/P‐ReaFLP. The valence bond state correlation diagram (VBSCD) model developed by Shaik is used to rationalize the calculated results. The VBSCD findings demonstrate that in the present trapping reactions, the singlet triplet splitting ofG14F2plays a significant role in influencing its reaction barrier and reaction enthalpy. Our theoretical results demonstrate that the relationship between the geometrical parameters of the transition states and the corresponding reaction free energy barriers agrees well with the findings based on the Hammond postulate.
Detection of hemoglobin H disease by long molecule sequencing
Authors: Li Youqiong , Liang Liang , Qin Ting , Tian Mao 
Published: September 2022

AbstractBackgroundHemoglobin H (Hb H) disease is a moderate‐to‐severe form of α‐thalassemia (α‐thal), and parts of patients may require intermittent transfusion therapy, especially during intercurrent illness. However, rare Hb H diseases remain undetected using routine methods being outside of the testing scope. In this study, we present an approach to detecting Hb H disease by long molecule sequencing (LMS).MethodsA total of 206 known genotype samples were collected and carried to blind detected by LMS on the PacBio Sequel platform. Circular consensus sequencing reads were aligned to the hg19 reference genome using Free‐Bayes finished LMS. LMS accuracy would be compared with routine methods, including Gap‐PCR and PCR‐Reverse dot blot hybridization (PCR–RDB).ResultsThe assay could detect carriers of both deletion and point mutations. It had an overall accuracy of 100% when compared with routine methods. In addition, LMS detected six mutations based on routine methods and corrected three case results. Hb H diseases were identified using LMS, whether a common or rare genotype, a deletion or non‐deletion genotype. However, two cases of Hb H disease were misdiagnosed using routine methods.ConclusionsLong molecule sequencing can be suggested as a rapid and reliable assay to detect probable carriers of hemoglobinopathies. LMS accurately identified the common and rare genotypes of Hb H disease.
Hippocampal interlamellar cell–cell connectome that counts
Authors: Pak Sojeong , Jang Doohyeong , Lee Jinho , Choi Gona , Shin Hongseong , Yang Sungchil , Yang Sunggu 
Published: September 2022

AbstractThe hippocampus is regarded as a cognition hub, particularly for learning and memory. Previously, neuronal mechanisms underlying various cognitive functions are delineated with the lamellar hippocampal circuitry, dentate gyrus—CA3 or CA2—CA1, within the transverse plane. More recently, interlamellar (often referred to as longitudinal) projections have received intensive attention to help understand signal convergence and divergence in cognition and behavior. Signal propagation along the longitudinal axis is evidenced by axonal arborization patterns and synaptic responses to electro‐ and photo‐stimulation, further demonstrating that information flow is more enriched in the longitudinal plane than the transverse plane. Here, we review the significance of longitudinal connections for cognition, discuss a putative circuit mechanism of place coding, and suggest the reconceptualization of the hippocampal circuitry.
Influence of Renal Function on Phosphoramide Mustard Exposure: A Nonlinear Mixed‐Effects Analysis
Authors: Jaber Mutaz M. , Takahashi Takuto , Kirstein Mark N. , Al‐Kofahi Mahmoud , Jacobson Pamala A. , Brundage Richard C. 
Published: September 2022

AbstractPhosphoramide mustard (PM) is the final cytotoxic metabolite formed from the parent compound cyclophosphamide through a complex metabolic pathway, primarily through hepatic metabolism. Little is known about the effect of renal elimination on the disposition of PM. We evaluated the effect of renal function on PM exposure after single doses of cyclophosphamide in 85 patients undergoing allogeneic hematopoietic cell transplantation using nonlinear mixed‐effects modeling. Mixed linear and nonlinear elimination pathways were required to adequately describe the disposition of PM. Creatinine clearance (CrCL) was incorporated as a covariate associated with first‐order elimination, representing renal clearance (ClR) of PM. For a 70‐kg patient, ClR was 14.9 L/h, Volume of distribution was 525 L, maximum rate was 81.2 mg/h, and the concentration to achieve 50% of maximum rate was 0.51 mg/L. We conducted simulations to explore the impact of CrCL as a measure of renal function and observed that when CrCL decreases from 120 to 40 mL/min, PM area under the plasma concentration–time curve (AUC) from time 0 to 8 hours and AUC increases by 9.2% and 80.9% on average after a single dose, respectively. Our data suggest that renal function has limited influence on PM exposure during the first 8 hours after dosing but has a large impact on the total exposure. Dose adjustment of cyclophosphamide may not be necessary in hematopoietic cell transplant recipients with moderate to severe kidney dysfunction to attain targeted exposures based on AUC from time 0 to 8 hours. However, dose reduction may be necessary if demonstrated at some future time that total AUC is a better surrogate for safety or toxicity.
Sarcopenia and mild cognitive impairment among elderly adults: The first longitudinal evidence from CHARLS
Authors: Hu Yisong , Peng Wenjia , Ren Rujing , Wang Ying , Wang Gang 
Published: September 2022

AbstractBackgroundThe association between sarcopenia and mild cognitive impairment (MCI) among elderly adults in China remains unclear. The present study aimed to examine the association based on a nationally representative large‐scale survey.MethodsThe study used two waves of data from China Health and Retirement Longitudinal Study (CHARLS) in 2015 and 2018. All subjects met the inclusion criteria were classified based on Asia Working Group for Sarcopenia 2019 criteria. Aging‐associated cognitive decline is used to define MCI, and cognitive function is measured based on four dimensions: orientation, computation, memory, and drawing. OLS and logistic regression model were conducted to analyse the cross‐sectional association between sarcopenia and different cognitive functions. Logistic regression model was conducted to analyse the longitudinal association between sarcopenia and MCI.ResultsTotally, 5715 participants aged over 60 years (43.8% women; mean age 67.3 ± 6.0 years) were enrolled in a cross‐sectional association study in 2015, and further 2982 elderly adults were followed up in 2018. During the period, sarcopenia and possible sarcopenia increased from 8.5% to 29.6%. Scores of cognitive and four dimensions (orientation, computation, memory, and drawing) exhibited a decreasing trend from non‐sarcopenia to sarcopenia (P < 0.001). In the fully adjusted OLS regression model, scores of four dimensions were lower in possible sarcopenia and sarcopenia groups when compared with the non‐sarcopenia group (P < 0.05) respectively. The incidence of MCI was 10.1%, 16.5%, and 24.2% for non‐sarcopenia, possible sarcopenia, and sarcopenia groups from 2015 to 2018, with a significantly statistical difference (P < 0.001). Logistic regression model revealed an odds ratio of 1.43 [95% confidence interval (CI): 1.06–1.91, P = 0.017] for the possible sarcopenia group and 1.72 (95% CI: 1.04–2.85, P = 0.035) for sarcopenia group when compared with the non‐sarcopenia group.ConclusionsSarcopenia is associated with worse cognitive impairment, which provided new evidence for a strong association that warrants further research into mechanistic insights.
Understanding real‐world treatment patterns and clinical outcomes in AL amyloidosis patients diagnosed in Canada: A population‐based cohort study
Authors: Jimenez‐Zepeda Victor H. , Reece Donna , Rigo Rodrigo , Gogna Priyanka , Kong Shiying , Hu Xun Yang , Chapani Parv , Cheung Winson Y. , Brenner Darren R. , Plante Richard , Shi Kun , Husain Asad , Tankala Dipti , Boyne Devon J. 
Published: September 2022

AbstractAmyloid light chain (AL) amyloidosis is a rare and chronic bone marrow disorder. Existing claims data can be used to help understand the real‐world treatment patterns and outcomes of this patient population. Various population‐based administrative databases in Alberta, Canada were queried from 2010 to mid‐2019 to identify cases of AL amyloidosis. Baseline patient and disease characteristics, sequencing of pharmacologic therapies, overall survival, and healthcare resource utilization were evaluated. A total of 215 individuals with AL amyloidosis were included. Among patients diagnosed between 2012 and 2019, 149 (85.1%) initiated first‐line, 67 (38.3%) initiated second‐line, 22 (12.6%) initiated third‐line, and 11 (6.3%) initiated fourth‐line systemic therapy. In the first‐line setting, 99/149 (66.4%) received bortezomib, cyclophosphamide, and dexamethasone (CyBorD) and 21/149 (14.1%) received another bortezomib‐based regimen. Survival from time of diagnosis improved over time, with a median overall survival of 25.8 months (95% CI: 9.8, 57.1) for individuals diagnosed in 2010–2011 versus 52.1 months (95% CI: 25.6, NA) for those diagnosed in 2012–2019. Despite this improvement, the proportion of individuals diagnosed in 2012–2019 who survived beyond five‐years remained low (5‐year survival: 48.4%; 95% CI: 40.9, 57.2) which highlights an unmet need for more efficacious therapies.
Synthesis and biological assessment of some fused Pyran derivatives
Authors: Shamili Sriramoju , Siddoju Kavitha , Srinivas Avula , Farheen Sd. Ishrath 
Published: September 2022

AbstractPyran was formed by reacting methyl 3‐methoxyacrylate (1) with 2‐benzylidenemalanonitrile to form compound 2. The pyrano derivatives 3–6 were obtained by reacting the second molecule with 2‐benzylidenemalanonitrile, carbon disulfide, formamide, and benzylidene cyclohexanone. Compound (2) interacted with ethyl chloroacetate to form compound 8, which then cyclized in the presence of sodium ethoxide to form compound 9. Compound 7 was formed when compound (2) was treated with acetic acid in the presence of sulfuric acid and reacted with ethylchloroacetate to form compound 10 and then was converted to compound 11 by the addition of sodium ethoxide. Analytical and spectral data have been used to determine the structures of the newly synthesized substances and they were then tested for their antibacterial and antioxidant activities. In terms of antioxidant activity, compounds 2 and 8 were found to have the greatest and lowest levels, respectively, against Enterobacter aerogenes.