bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biosynthesis and antifungal activity of fungus-induced O-methylated flavonoids in maize
Authors: Förster Christiane , Handrick Vinzenz , Ding Yezhang , Nakamura Yoko , Paetz Christian , Schneider Bernd , Castro-Falcón Gabriel , Hughes Chambers C , Luck Katrin , Poosapati Sowmya , Kunert Grit , Huffaker Alisa , Gershenzon Jonathan , Schmelz Eric A , Köllner Tobias G 
Published: October 2021

Abstract
Fungal infection of grasses, including rice (Oryza sativa), sorghum (Sorghum bicolor), and barley (Hordeum vulgare), induces the formation and accumulation of flavonoid phytoalexins. In maize (Zea mays), however, investigators have emphasized benzoxazinoid and terpenoid phytoalexins, and comparatively little is known about flavonoid induction in response to pathogens. Here, we examined fungus-elicited flavonoid metabolism in maize and identified key biosynthetic enzymes involved in the formation of O-methylflavonoids. The predominant end products were identified as two tautomers of a 2-hydroxynaringenin-derived compound termed xilonenin, which significantly inhibited the growth of two maize pathogens, Fusarium graminearum and Fusarium verticillioides. Among the biosynthetic enzymes identified were two O-methyltransferases (OMTs), flavonoid OMT 2 (FOMT2), and FOMT4, which demonstrated distinct regiospecificity on a broad spectrum of flavonoid classes. In addition, a cytochrome P450 monooxygenase (CYP) in the CYP93G subfamily was found to serve as a flavanone 2-hydroxylase providing the substrate for FOMT2-catalyzed formation of xilonenin. In summary, maize produces a diverse blend of O-methylflavonoids with antifungal activity upon attack by a broad range of fungi.
Unequal Ties: Immigrants’ Initial Social Capital and Labor Market Stratification
Authors: Park Sung S , Lai Tianjian , Waldinger Roger D 
Published: October 2021

Abstract
Social capital (SC) plays a fundamental role in immigration by easing entry into a new environment. We advance a novel approach to assessing the role of SC for immigrants’ labor market incorporation. First, we isolate the impact of SC activation from the mere presence of potential help. Second, we disentangle the diverse components of migration-related SC by distinguishing between individual migration- (IM) and community migration-level (CM) connections in the country of destination. Third, we trace the roles of IM SC and CM SC across multiple labor market outcomes, ranging from the search to secure the first job to the quality of the first job to longer-term occupational mobility. Absent activation, IM SC has virtually no impact on any of the outcomes. Rather, migrants’ IM SC yield their fundamental impact when activated, contributing to a successful job search while steering them into first jobs that are of lower-quality relative to their pre-migration occupation. By contrast, CM SC facilitates the initial job search and filters immigrants into higher-quality first jobs. Moreover, immigrants who arrive when CM SC is at its most mature stage reap the clearest benefits in improving their occupational status. These findings underscore the importance of both early settlement IM SC and CM SC in the processes of immigrants’ labor market stratification.
Successful healthcare transition for youth with special healthcare needs is a team effort
Authors: Cady Rhonda G. , Erickson Catherine , Harris Debbi Simmons , Nickelsen Tracy 
Published: October 2021

Abstract:
NPs care for persons across the age continuum and transitions commonly occur. Some are unexpected, like hospitalizations for acute illness or injury. Others are an expected consequence of growing up, like moving from pediatric to adult care models. Understanding the factors impacting healthcare transition is critical for successful outcomes.
ZIP12 Contributes to Hypoxic Pulmonary Hypertension by Driving Phenotypic Switching of Pulmonary Artery Smooth Muscle Cells
Authors: Zhu Tiantian , Wang Xuan , Zheng Zijie , Quan Jinping , Liu Yuhao , Wang Yuting , Liu Tianheng , Liu Xu , Wang Mi , Zhang Zheng 
Published: October 2021

Abstract:
ZIP12, a plasmalemmal zinc transporter, reportedly promotes pulmonary vascular remodeling (PVR) by enhancing proliferation of pulmonary artery smooth muscle cells (PASMCs). However, the mechanisms of ZIP12 facilitating PASMCs proliferation remain incompletely appreciated. It has been acknowledged that proliferation-predisposing phenotypic switching of PASMCs can lead to PVR. Given that hypoxia triggers phenotypic switching of PASMCs and ZIP12 mediates PVR, this study aims to explore whether ZIP12-mediated phenotypic switching of PASMCs contributes to hypoxia-induced PVR. Rats were exposed to hypoxia (10% O2) for 3 weeks to induce PVR, and primary rat PASMCs were cultured under hypoxic condition (3% O2) for 48 hours to induce proliferation. Immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and Western blot analysis were performed to detect the expression of target mRNAs and proteins. EdU incorporation and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay were conducted to measure the proliferation of PASMCs. Hypoxia upregulated ZIP12 expression (both mRNA and protein) in pulmonary arteries and PASMCs. Knockdown of ZIP12 inhibited phenotypic switching of PASMCs induced by hypoxia. We propose that HIF-1α/ZIP12/pERK pathway could represent a novel mechanism underlying hypoxia-induced phenotypic switching of PASMCs. Therapeutic targeting of ZIP12 could be exploited to treat PVR.
Vaginal mesh hysteropexy: a review
Authors: DiCarlo-Meacham Angela , Mazloomdoost Donna 
Published: October 2021

Purpose of review
Pelvic organ prolapse surgery is performed via native tissue or graft augmented repair. Graft augmentation with synthetic mesh was introduced to improve long-term surgical outcomes compared with vaginal native tissue repairs. Vaginal hysteropexy has recently become increasingly popular due to patient preference and an improved morbidity profile over hysterectomy, while maintaining comparable efficacy. As long-term outcomes remain unanswered, mesh augmentation to vaginal hysteropexy has sought to improve efficacy while minimizing complications.

Recent findings
Recent studies have demonstrated superiority of vaginal mesh hysteropexy to vaginal hysterectomy with native tissue vault suspension. Short-term follow-up of vaginal mesh hysteropexy has also demonstrated lower blood loss and operative time with improved vaginal length compared with hysterectomy. Mesh exposure rates across studies were low and comparable to those of abdominally placed prolapse mesh.

Summary
Vaginal mesh hysteropexy is a comparably well tolerated and effective surgical treatment option for women with uterovaginal prolapse. Although vaginal mesh kits are not commercially available, this procedure may be a viable treatment option in select patients.
Neuropathogenesis of severe acute respiratory syndrome coronavirus 2
Authors: Patel Payal B. , Bearden David 
Published: October 2021

Purpose of review
The purpose of this review is to address our current understanding of the pathophysiology of neurologic injury resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection on the developing nervous system.

Recent findings
SARS-CoV2 may enter the brain through three potential mechanisms: transsynaptic spread from the olfactory bulb following intranasal exposure, migration across the blood–brain barrier through endothelial cell infection, and migration following disruption of the blood–brain barrier from resulting inflammation. SARS-CoV2 does not appear to directly infect neurons but rather may produce an inflammatory cascade that results in neuronal injury. Additionally, autoantibodies targeting neuronal tissue resulting from the immune response to SARS-CoV2 are present in select patients and may contribute to central nervous system (CNS) injury.

Summary
These findings suggest that neuronal injury during SARS-CoV2 infection is immune mediated rather than through direct viral invasion. Further multimodal studies evaluating the pathophysiology of neurologic conditions in pediatric patients specifically following SARS-CoV2 infection are needed to improve our understanding of mechanisms driving neurologic injury and to identify potential treatment options.
Coping Under Extreme Conditions
Authors: Eterović Marija , Lucijanić Dijana , Kranjčević Matija , Marinić Igor , Marinić Lana Mužinić 
Published: October 2021

Abstract
The role of coping dispositions in predicting coping with a potentially traumatic event (PTE; situational coping) has been bypassed. We explored the degree to which the dispositional coping of 103 mountain rescuers predicted coping with their last PTE. Dispositional venting of emotions and turning to religion explained more than half of the variance in the use of the same strategy to cope with the PTE. Most coping dispositions predicted about 30% to 40% of the variance in comparable situational coping. Dispositional denial did not predict situational use of denial. Multivariate dispositional coping style explained a great deal of the variance in most situational coping responses. Dispositional coping was more relevant than situational to participants' global psychological distress and explained about one-fourth of the variance in distress. These results suggest that most dispositional styles considerably impact coping with PTE but to the extent that varies across different coping styles.
Olfactory Dysfunction
Authors: Kaya Ender , Göker Ayşe Enise 
Published: October 2021

Abstract
Olfactory disorders may be observed together with cognitive impairment in patients with major depressive disorder (MDD). This study compared olfactory performances between patients with MDD and healthy controls and investigated the relationship between olfactory performance and subjective cognitive impairment in these patients. This study included 52 patients diagnosed with MDD and 46 healthy controls. The participants were evaluated in terms of their olfactory capacities (threshold, discrimination, and identification), subjective cognitive impairment, and depression. Although the olfactory threshold (OT) and olfactory discrimination scores were lower in patients with MDD compared with those in the control group, their olfactory identification scores did not differ significantly. OT was negatively correlated with subjective cognitive impairment and may serve as a determinant for subjective cognitive changes. Consequently, patients with MDD had lower olfactory performances compared with healthy controls. Finally, OT may be a component of subjective cognitive impairment in MDD.
The Relationship Between Degree of Nasal Septum Deviation With Sinonasal Structures and Variations
Authors: Atsal Görkem , Demir Emine , Yildirim Oben , Edizer Deniz Tuna , Olgun Levent 
Published: October 2021

Abstract:
We aimed to evaluate whether the nasal septum deviation affects the development of sinonasal structures. Patients who had undergone paranasal sinus computed tomography (PNS-CT) imaging due to nasal obstruction were divided into 3 groups according to the septal deviation angle; group I: 0° to 9°, group II: 10° to 15°, and group III: >15°. The features of sinonasal structures were recorded when evaluating PNS-CT. There were totally 234 patients, 119 patients in group I, 68 in group II, and 47 in group III. On the opposite side of the deviation, keros 3 was significantly more in group III (P < 0.001). Although the incidence of concha bullosa and agger nasi cell were not affected by the degree of deviation (P > 0.05), the incidence of Haller and Onodi cells were significantly higher in group III (P < 0.001). In addition, all cells were observed more in the opposite side of the deviation in each group (P < 0.001). Maxillary sinus retention cysts and hypoplasia of maxillary and frontal sinuses, as an indicator of the low pneumatization of the sinuses, are seen more on the same side of nasal septum deviation, increasing with the degree of deviation increases (P < 0.001). Nasal septum deviation affects the development of sinonasal structures by affecting the pneumatization. Preoperative PNS-CT evaluation is important in order to be aware of the situations that we may encounter during surgery and to provide adequate treatment.
Neuroprotective effect of paeoniflorin in the mouse model of Parkinson’s disease through α-synuclein/protein kinase C δ subtype signaling pathway
Authors: Guo Kedong , Zhang Yingbo , Li Libo , Zhang Jingyan , Rong Hua , Liu Deshui , Wang Junping , Jin Ming , Luo Nan , Zhang Xiaojie 
Published: October 2021

Objectives
Paeoniflorin, an active component of Radix Paeoniae Alba, has a neuroprotective effect in Parkinson’s animal models. However, its mechanism of action remains to be determined.

Methods
In this study, we hypothesized that the neuroprotective effect of paeoniflorin occurs through the α-synuclein/protein kinase C δ subtype (PKC-δ) signaling pathway. We tested our hypothesis in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson’s disease. We evaluated the effects of paeoniflorin on the expression levels of signal components of the α-synuclein/PKC-δ pathway, cellular apoptosis and motor performance.

Results
Our results demonstrated that paeoniflorin restored the motor performance impairment caused by MPTP, inhibited apoptosis, and protected the ultrastructure of neurons. Paeoniflorin treatment also resulted in the dose-dependent upregulation of an antiapoptotic protein, B-cell lymphoma-2, at the mRNA and protein levels, similar to the effects of the positive control, selegiline. In contrast, paeoniflorin treatment downregulated the expression of pro-apoptotic proteins BCL2-Associated X2, α-synuclein, and PKC-δ at the mRNA and protein levels, as well as the level of the activated form of nuclear factor kappa B (p-NF-κB p65).

Conclusions
Thus, our results showed that paeoniflorin exerts its neuroprotective effect by regulating the α-synuclein/PKC-δ signaling pathway to reduce neuronal apoptosis.
Optimal ECG-lead selection increases generalizability of deep learning on ECG abnormality classification
Authors: Lai Changxin , Zhou Shijie , Trayanova Natalia A. 
Published: October 2021

Deep learning (DL) has achieved promising performance in detecting common abnormalities from the 12-lead electrocardiogram (ECG). However, diagnostic redundancy exists in the 12-lead ECG, which could impose a systematic overfitting on DL, causing poor generalization. We, therefore, hypothesized that finding an optimal lead subset of the 12-lead ECG to eliminate the redundancy would help improve the generalizability of DL-based models. In this study, we developed and evaluated a DL-based model that has a feature extraction stage, an ECG-lead subset selection stage and a decision-making stage to automatically interpret multiple common ECG abnormality types. The data analysed in this study consisted of 6877 12-lead ECG recordings from CPSC 2018 (labelled as normal rhythm or eight types of ECG abnormalities, split into training (approx. 80%), validation (approx. 10%) and test (approx. 10%) sets) and 3998 12-lead ECG recordings from PhysioNet/CinC 2020 (labelled as normal rhythm or four types of ECG abnormalities, used as external text set). The ECG-lead subset selection module was introduced within the proposed model to efficiently constrain model complexity. It detected an optimal 4-lead ECG subset consisting of leads II, aVR, V1 and V4. The proposed model using the optimal 4-lead subset significantly outperformed the model using the complete 12-lead ECG on the validation set and on the external test dataset. The results demonstrated that our proposed model successfully identified an optimal subset of 12-lead ECG; the resulting 4-lead ECG subset improves the generalizability of the DL model in ECG abnormality interpretation. This study provides an outlook on what channels are necessary to keep and which ones may be ignored when considering an automated detection system for cardiac ECG abnormalities.
This article is part of the theme issue ‘Advanced computation in cardiovascular physiology: new challenges and opportunities’.
Functional brain–heart interplay extends to the multifractal domain
Authors: Catrambone Vincenzo , Barbieri Riccardo , Wendt Herwig , Abry Patrice , Valenza Gaetano 
Published: October 2021

The study of functional brain–heart interplay has provided meaningful insights in cardiology and neuroscience. Regarding biosignal processing, this interplay involves predominantly neural and heartbeat linear dynamics expressed via time and frequency domain-related features. However, the dynamics of central and autonomous nervous systems show nonlinear and multifractal behaviours, and the extent to which this behaviour influences brain–heart interactions is currently unknown. Here, we report a novel signal processing framework aimed at quantifying nonlinear functional brain–heart interplay in the non-Gaussian and multifractal domains that combines electroencephalography (EEG) and heart rate variability series. This framework relies on a maximal information coefficient analysis between nonlinear multiscale features derived from EEG spectra and from an inhomogeneous point-process model for heartbeat dynamics. Experimental results were gathered from 24 healthy volunteers during a resting state and a cold pressor test, revealing that synchronous changes between brain and heartbeat multifractal spectra occur at higher EEG frequency bands and through nonlinear/complex cardiovascular control. We conclude that significant bodily, sympathovagal changes such as those elicited by cold-pressure stimuli affect the functional brain–heart interplay beyond second-order statistics, thus extending it to multifractal dynamics. These results provide a platform to define novel nervous-system-targeted biomarkers.
This article is part of the theme issue ‘Advanced computation in cardiovascular physiology: new challenges and opportunities’.
Intraoperative Hydromorphone Decreases Post-Operative Pain Who Would Have Thought? An Instrumental Variable Analysis
Authors: Ershoff Brent 
Published: October 2021

AbstractBackgroundA growing body of literature suggests that intraoperative opioid administration can lead to both increased post-operative pain and opioid requirements. However, there has been minimal data regarding the effects of the intraoperative administration of intermediate duration opioids such as hydromorphone on post-operative outcomes. Causal inference using observational studies is often hampered by unmeasured confounding, where classical adjustment techniques, such as multivariable regression, are insufficient. Instrumental variable analysis is able to generate unbiased causal effect estimates in the presence of unmeasured confounding, assuming a valid instrumental variable can be found. We previously demonstrated, using a natural experiment, how hydromorphone presentation dose, i.e. the unit dose provided to the clinician, affects intraoperative administration dose, with the switch from a 2-mg to a 1-mg vial associated with decreased administration. As the change in hydromorphone presentation dose was unrelated to any external factors, presentation dose could serve as an instrumental variable to estimate the effect of intraoperative hydromorphone administration dose on post-operative outcomes.MethodsIn this observational study with 6,751 patients, an instrumental variable analysis was employed to estimate the causal effect of an increased intraoperative administration dose of hydromorphone on post-operative pain and opioid administration. The study population included patients who received intraoperative hydromorphone as part of an anesthetic at the University of California, Los Angeles, from October 2016 to November 2018. Before July 2017, hydromorphone was available as a 2-mg unit dose. From July 1, 2017 to November 20, 2017, hydromorphone was only available in a 1-mg unit dose. A two-stage least squares regression analysis was performed to estimate the effect of intraoperative hydromorphone administration dose on post-operative pain scores and opioid administration.ResultsAn increase in hydromorphone administration caused a statistically significant decrease in Post-Anesthesia Care Unit pain scores as well as maximum and mean pain scores on post-operative days one and two, without a statistically significant effect on post-operative opioid administration. Various sensitivity analyses support the validity of the instrumental variable assumptions and suggest that the results are robust against violations of these assumptions.ConclusionsThe results of this study suggests that the intraoperative administration of intermediate duration opioids do not cause the same effects as short acting opioids with respect to post-operative pain. Instrumental variables, when identified, can be invaluable in estimating causal effects using observation data whereby unmeasured confounding is likely present.
Tools for the assessment of quality and risk of bias in Mendelian randomization studies: a systematic review
Authors: Spiga Francesca , Gibson Mark , Dawson Sarah , Smith George Davey , Munafò Marcus R , Higgins Julian PT 
Published: October 2021

AbstractBackgroundThe use of Mendelian randomization (MR) in epidemiology has increased considerably in recent years, with a subsequent increase in systematic reviews of MR studies. We conducted a systematic review of tools designed for risk of bias and/or quality of evidence assessment in (MR) studies, and a review of systematic reviews of MR studies.MethodsWe systematically searched MEDLINE, Embase, the Web of Science, preprints servers and Google Scholar for articles containing tools for assessing, conducting and/or reporting MR studies. We also searched for systematic reviews and protocols of systematic reviews of MR. From eligible articles we collected data on tool characteristics and content, as well as details of narrative description of bias assessment.ResultsOur searches retrieved 2464 records to screen, from which 14 tools, 35 systematic reviews and 38 protocols were included in our review. Seven tools were designed for assessing risk of bias/quality of evidence in MR studies and evaluation of their content revealed that all seven tools addressed the three core assumptions of instrumental variable analysis, violation of which can potentially introduce bias in MR analysis estimates.ConclusionsWe present an overview of tools and methods to assess risk of bias/quality of evidence in MR analysis. As none of these methods has been tested and validated for general use, we do not provide recommendations on their use. Our findings should raise awareness about the importance of bias related to MR analysis and provide information that is useful for assessment of MR studies in the context of systematic reviews.