bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel chemical genetic approach reveals paralog-specific role of ERK1/2 in mouse embryonic stem cell fate control
Authors: Hu Liang , Xiao Xiong , Huang Wesley , Zhou Tao , Chen Weilu , Zhang Chao , Ying Qi-Long 
Published: July 2024

Introduction: Mouse embryonic stem cell (ESC) self-renewal can be maintained through dual inhibition of GSK3 and MEK kinases. MEK has two highly homologous downstream kinases, extracellular signal-regulated kinase 1 and 2 (ERK1/2). However, the exact roles of ERK1/2 in mouse ESC self-renewal and differentiation remain unclear.Methods: We selectively deleted or inhibited ERK1, ERK2, or both using genetic and chemical genetic approaches combined with small molecule inhibitors. The effects of ERK paralog-specific inhibition on mouse ESC self-renewal and differentiation were then assessed.Results: ERK1/2 were found to be dispensable for mouse ESC survival and self-renewal. The inhibition of both ERK paralogs, in conjunction with GSK3 inhibition, was sufficient to maintain mouse ESC self-renewal. In contrast, selective deletion or inhibition of only one ERK paralog did not mimic the effect of MEK inhibition in promoting mouse ESC self-renewal. Regarding ESC differentiation, inhibition of ERK1/2 prevented mesendoderm differentiation. Additionally, selective inhibition of ERK1, but not ERK2, promoted mesendoderm differentiation.Discussion: These findings suggest that ERK1 and ERK2 have both overlapping and distinct roles in regulating ESC self-renewal and differentiation. This study provides new insights into the molecular mechanisms of ERK1/2 in governing ESC maintenance and lineage commitment, potentially informing future strategies for controlling stem cell fate in research and therapeutic applications.
Clinical utility of metagenomic next-generation sequencing in the diagnosis of invasive pulmonary aspergillosis in acute exacerbation of chronic obstructive pulmonary disease patients in the intensive care unit
Authors: Niu Siqiang , Liu Dezhi , Yang Yan , Zhao Limin 
Published: July 2024

ObjectiveTo explore the clinical utility of metagenomic next-generation sequencing (mNGS) in diagnosing invasive pulmonary aspergillosis (IPA) among patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in the intensive care unit (ICU).MethodsA retrospective analysis was conducted on patients with AECOPD admitted to the ICU of Xinxiang Central Hospital in Henan Province, China, between March 2020 and September 2023, suspected of having IPA. Bronchoalveolar lavage fluid (BALF) samples were collected for fungal culture, the galactomannan (GM) test, and mNGS. Based on host factors, clinical features, and microbiological test results, patients were categorized into 62 cases of IPA and 64 cases of non-IPA. Statistical analysis was performed to compare the diagnostic efficacy of fungal culture, the serum and BALF GM test, and mNGS detection for IPA in patients with AECOPD.Results1. The sensitivity and specificity of mNGS in diagnosing IPA were 70.9% and 71.8% respectively, with the sensitivity of mNGS surpassing that of fungal culture (29.0%, P&lt;0.01), serum GM test (35.4%, P&lt;0.01), and BALF GM test (41.9%, P&lt;0.05), albeit with slightly lower specificity compared to fungal culture (90.6%, P &gt;0.05), serum GM test (87.5%, P &gt;0.05), and BALF GM test (85.9%, P &gt;0.05).Combining fungal culture with the GM test and mNGS resulted in a sensitivity of 80.6% and a specificity of 92.2%, underscoring a superior diagnostic rate compared to any single detection method. 2.mNGS accurately distinguished strains of the Aspergillus genus. 3.The area under the ROC curves of mNGS was 0.73, indicating good diagnostic performance. 4.The detection duration for mNGS is shorter than that of traditional fungal culture and GM testing.ConclusionmNGS presents a pragmatic and highly sensitive approach, serving as a valuable complementary tool to conventional microbiological tests (CMT). Our research demonstrated that, compared to fungal culture and GM testing, mNGS exhibits superior diagnostic capability for IPA among patients with AECOPD. Integration of mNGS with established conventional methods holds promise for improving the diagnosis rate of IPA.
Stevens-Johnson syndrome and toxic epidermal necrolysis associated with immune checkpoint inhibitors: a systematic review
Authors: Zhou Jia , Wang Chuan-Peng , Li Jun , Zhang Han-Lin , He Chun-Xia 
Published: July 2024

IntroductionStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare yet life-threatening adverse events associated with immune checkpoint inhibitors (ICIs). This systematic review synthesizes the current literature to elucidate the clinical characteristics and outcomes of patients with ICI-related SJS/TEN.MethodsWe conducted a thorough search across databases including Embase, Web of Science, Cochrane, MEDLINE, Scopus, and PubMed. Selection criteria focused on reports of SJS/TEN among cancer patients treated with ICIs, analyzing clinical manifestations, therapeutic interventions, and outcomes.ResultsOur analysis included 47 articles involving 50 patients with ICI-related SJS/TEN. The cohort had a mean age of 63 years, with a slight male predominance (54%). Most patients had melanoma or non-small cell lung cancer. SJS/TEN typically occurred early, with a median onset of 23 days post-ICI initiation. Treatment primarily involved systemic corticosteroids and intravenous immunoglobulins. The overall mortality rate was 20%, higher for TEN at 32%, with infections and tumor progression as leading causes. Median time from onset to death was 28 days. Survivors experienced a median re-epithelization time of 30 days, positively correlated with the extent of epidermal detachment (rs = 0.639, p = 0.009). Deceased patients exhibited a significantly higher proportion of TEN (90% vs. 48%, p = 0.029) and a larger epidermal detachment area (90% vs. 30% of the body surface area [BSA], p = 0.005) compared to survivors. The combination therapy group showed a higher proportion of TEN compared to corticosteroid monotherapy or non-corticosteroid therapy groups (72% vs. 29% and 50%, p = 0.01), with no significant differences in mortality or re-epithelization time. Dual ICI therapy resulted in a higher TEN rate than single therapy (100% vs. 50%, p = 0.028). Among single ICI therapies, the sintilimab-treated group trended towards a higher TEN rate (75% vs. 40-50%, p = 0.417), a larger detachment area (90% vs. 30-48% of BSA, p = 0.172), and a longer re-epithelization time (44 vs. 14-28 days, p = 0.036) compared to other ICI groups, while mortality rates remained similar.ConclusionICI-related SJS/TEN substantially impacts patient outcomes. Prospective clinical trials are critically needed to further clarify the pathogenesis and optimize therapeutic regimens.
Causal effects of gut microbiota on risk of interstitial cystitis: a two-sample Mendelian randomization study
Authors: Gao Jianguo , Shao Sihai , Shen Yuefan 
Published: July 2024

BackgroundThe correlation between gut microbiota and interstitial cystitis has garnered significant attention in previous studies. Nevertheless, the causal relationship between them remains to be clarified.MethodsGenetic variation serves as a tool in Mendelian randomization analyses, facilitating the inference of causal relationships between exposure factors and disease outcomes. In this study, summary statistics derived from a comprehensive genome-wide association study conducted by the MiBioGen consortium were utilized as exposure factors, while interstitial cystitis data sourced from the GWAS Catalog served as the disease outcome. Then, a two-sample Mendelian randomization analysis was performed by applying inverse variance-weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. In addition, heterogeneity and horizontal pleiotropy were excluded by sensitivity analysis.ResultsIVW results confirmed that genus Haemophilus (OR = 2.20, 95% CI: 1.16–4.15, p = 0.015), genus Butyricimonas (OR = 2.26, 95% CI: 1.15–4.45, p = 0.018), genus Bacteroides (OR = 4.27, 95% CI: 1.36–13.4, p = 0.013) and Coprococcus1 (OR = 3.39, 95% CI: 1.28–8.99, p = 0.014) had a risk effect on interstitial cystitis. Sensitivity analysis did not find outlier SNPs.ConclusionOur analysis has identified a causal relationship between specific genera and interstitial cystitis. However, further validation through randomized controlled trials is essential to substantiate these findings.
Object recognition in primates: what can early visual areas contribute?
Authors: Quaia Christian , Krauzlis Richard J. 
Published: July 2024

IntroductionIf neuroscientists were asked which brain area is responsible for object recognition in primates, most would probably answer infero-temporal (IT) cortex. While IT is likely responsible for fine discriminations, and it is accordingly dominated by foveal visual inputs, there is more to object recognition than fine discrimination. Importantly, foveation of an object of interest usually requires recognizing, with reasonable confidence, its presence in the periphery. Arguably, IT plays a secondary role in such peripheral recognition, and other visual areas might instead be more critical.MethodsTo investigate how signals carried by early visual processing areas (such as LGN and V1) could be used for object recognition in the periphery, we focused here on the task of distinguishing faces from non-faces. We tested how sensitive various models were to nuisance parameters, such as changes in scale and orientation of the image, and the type of image background.ResultsWe found that a model of V1 simple or complex cells could provide quite reliable information, resulting in performance better than 80% in realistic scenarios. An LGN model performed considerably worse.DiscussionBecause peripheral recognition is both crucial to enable fine recognition (by bringing an object of interest on the fovea), and probably sufficient to account for a considerable fraction of our daily recognition-guided behavior, we think that the current focus on area IT and foveal processing is too narrow. We propose that rather than a hierarchical system with IT-like properties as its primary aim, object recognition should be seen as a parallel process, with high-accuracy foveal modules operating in parallel with lower-accuracy and faster modules that can operate across the visual field.
Intermediate catheter use is associated with intraprocedural rupture during coil embolization of ruptured intracranial aneurysms: a retrospective propensity score-matched study
Authors: Fuga Michiyasu , Ishibashi Toshihiro , Aoki Ken , Kato Naoki , Kan Issei , Hataoka Shunsuke , Nagayama Gota , Sano Tohru , Tanaka Toshihide , Murayama Yuichi 
Published: July 2024

IntroductionAn intermediate catheter (IMC) may pose a risk of intraprocedural rupture (IPR) during coil embolization of ruptured intracranial aneurysms (RIAs), because the pressure on the microcatheter and coil might be more direct. To verify this hypothesis, this study explored whether use of an IMC might correlate with an increased rate of IPR during coil embolization for RIAs.MethodsWe retrospectively reviewed 195 consecutive aneurysms in 192 patients who underwent initial coil embolization for saccular RIAs at our institution between January 2007 and December 2023. Patients were divided into two groups with aneurysms treated either with an IMC (IMC group) or without an IMC (non-IMC group). To investigate whether IMC use increased the rate of IPR, a propensity score-matched analysis was employed to control for age, sex, maximal aneurysm size, neck size, bleb formation, aneurysm location, proximal vessel tortuosity, balloon-assisted coiling, type of microcatheter, and type of framing coil.ResultsUltimately, 43 (22%) coil embolization used IMC. In univariate analysis, the incidence of IPR was significantly higher in the IMC group compared with the non-IMC group (14.0 vs. 3.3%, p = 0.016). Propensity score matching was successful for pairs of 26 aneurysms in the IMC group and 52 aneurysms in the non-IMC group. The incidence of IPR was still significantly higher in the IMC group than in the non-IMC group (23.1 vs. 3.8%, p = 0.015). No significant differences in the incidences of ischemic complications and IMC-related parent artery dissection were observed between the two groups.DiscussionWhen using IMC for coil embolization of RIAs, the surgeons should be more careful and delicate in manipulating the microcatheter and inserting the coils to avoid IPR.
Comparative effectiveness of non- pharmacological treatments in patients with persistent postural-perceptual dizziness: a systematic review and effect sizes analyses
Authors: Suica Zorica , Behrendt Frank , Ziller Carina , Gäumann Szabina , Schädler Stefan , Hilfiker Roger , Parmar Katrin , Gerth Hans Ulrich , Bonati Leo H. , Schuster-Amft Corina 
Published: July 2024

IntroductionThe patho-psychological mechanisms of persistent postural-perceptual dizziness (PPPD) appear to be very complex, and a multimodal, multidisciplinary approach is suggested for treating patients with PPPD. The aim of this review was to provide a comprehensive overview of non-pharmacological treatments and their comparative effectiveness in patients with PPPD.MethodsScopus, Web of Science, PsycINFO, Medline, Embase, CINAHL, Cochrane Library and ClinicalTrials.gov were searched in April 2022 with a search update in August 2023. Only randomized controlled trials (RCTs) were included. There was no restrictions regarding publication date. Two reviewers independently identified eligible trials, extracted data, double-checked all extracted information from the included articles and assessed the risk of bias using the Cochrane risk of bias tool. A qualitative synthesis was performed, considering methodological heterogeneity between trials. Finally, an effect size analysis was performed for each treatment comparison. The standardized mean differences (SMD) and their corresponding 95% confidence intervals (95%CI) were calculated for each trial using Review Manager 5.4.ResultsThirteen RCTs (618 patients with moderate or mild dizziness) out of 1,362 references describing seven different non-pharmacological comparisons were selected. Nine trials included patients with PPPD, and four trials included patients with functional dizziness. The trials used different interventions that were classified as: (1) psychotherapeutic interventions (cognitive behavioral therapy, patient education), (2) physiotherapeutic interventions/training (vestibular rehabilitation, optokinetic stimulation), (3) stimulation procedures (vagus nerve stimulation, transcranial direct current stimulation) and (4) device application (visual desensitization using personalized glasses). However, most of the trials investigated the effects of single interventions, rather than multimodal interdisciplinary treatment of patients with PPPD. The SMD for dizziness handicap and severity was between 0.04 and 0.52 in most trials. In one trial using visual desensitization, the SMD was 1.09 (strong effect on the severity of dizziness) and 1.05 (strong effect on dizziness handicap).DiscussionSeveral individual interventions have shown benefits in the treatment of patients with PPPD with small to moderate effects. However, the multimodal treatment or a combination of vestibular rehabilitation with visual desensitization, cognitive behavioral therapy including patient education, and medication support should be further investigated. Future trials should include a large sample size with severe dizziness, and provide a longer follow-up period.Clinical trial registrationPROSPERO CRD42022320344.
Modelling lung diffusion-perfusion limitation in mechanically ventilated SARS-CoV-2 patients
Authors: Miserocchi Giuseppe , Rezoagli Emanuele , Muñoz-Del-Carpio-Toia Agueda , Paricahua-Yucra Leydi Pamela , Zubieta-DeUrioste Natalia , Zubieta-Calleja Gustavo , Beretta Egidio 
Published: July 2024

This is the first study to describe the daytime evolution of respiratory parameters in mechanically ventilated COVID-19 patients. The data base refers to patients hospitalised in the intensive care unit (ICU) at Arequipa Hospital (Peru, 2335 m) in 2021. In both survivors (S) and non-survivors (NS) patients, a remarkable decrease in respiratory compliance was observed, revealing a proportional decrease in inflatable alveolar units. The S and NS patients were all hyperventilated and their SatO2 was maintained at &gt;90%. However, while S remained normocapnic, NS developed progressive hypercapnia. We compared the efficiency of O2 uptake and CO2 removal in the air blood barrier relying on a model allowing to partition between diffusion and perfusion limitations to gas exchange. The decrease in O2 uptake was interpreted as diffusion limitation, while the impairment in CO2 removal was modelled by progressive perfusion limitation. The latter correlated with the increase in positive end-expiratory pressure (PEEP) and plateau pressure (Pplat), leading to capillary compression, increased blood velocity, and considerable shortening of the air-blood contact time.
MeJA-induced hairy roots in Plumbago auriculata L. by RNA-seq profiling and key synthase provided new insights into the sustainable production of plumbagin and saponins
Authors: Li Yirui , Zhao Zi-an , Hu Ju , Lei Ting , Chen Qibing , Li Jiani , Yang Lijuan , Hu Di , Gao Suping 
Published: July 2024

Naturally synthesized secondary metabolites in plants are considered an important source of drugs, food additives, etc. Among them, research on natural plant medicinal components and their synthesis mechanisms has always been of high concern. We identified a novel medicinal floral crop, Plumbago auriculata L., that can be treated with methyl jasmonate (MeJA) for the rapid or sustainable production of natural bioactives from hairy roots. In the study, we globally analyzed the changes in the accumulation of plumbagin and others in the hairy roots of Plumbago auriculata L. hairy roots (PAHR) 15834 in P. auriculata L. based on 100 μmol/L of MeJA treatment by RNA-seq profiling, and we found that there was a significant increase in the accumulation of plumbagin and saponin before 24 h. To explain the principle of co-accumulation, it showed that MeJA induced JA signaling and the shikimic acid pathway, and the methylvaleric acid (MVA) pathway was activated downstream subsequently by the Mfuzz and weighted gene co-expression analysis. Under the shared metabolic pathway, the high expression of PAL3 and HMGR promoted the activity of the “gateway enzymes” phenylalanine ammonia lyase (PAL) and 3-hydroxy-3-methylglutaryl CoA reductase (HMGR), which respectively induced the high expression of key reaction enzyme genes, including chalcone synthase (CHS), isopentenyl diphosphate (IPP), and farnesyl pyrophosphate synthase (FPS), that led to the synthesis of plumbagin and saponin. We speculated that large amounts of ketones and/or aldehydes were formed under the action of these characteristic enzymes, ultimately achieving their co-accumulation through polyketone and high-level sugar and amino acid metabolism. The study results provided a theoretical basis for carrying out the factory refinement and biosynthesis of plumbagin and saponins and also provided new ideas for fully exploiting multifunctional agricultural crops and plants and developing new agricultural by-products.
Associations between media use at bedtime and sleep: a cross-sectional analysis on differences between girls and boys
Authors: Poulain Tanja , Hilbert Cornelia , Grundmann Annelie , Kiess Wieland 
Published: July 2024

ObjectivesThis study investigated associations between the use of electronic media and sleep in children and young adolescents, with a specific focus on the moderation of associations by sex and age.MethodsBetween 2021 and 2022, 453 10- to 14-year-old children participating in the LIFE Child cohort study (Germany) reported on their use of electronic media (daily screen time, use at bedtime, device ownership) and on their sleep difficulties (Sleep Self Report). Associations between media use and sleep as well as interactions with age and sex were assessed using linear regression analyses.ResultsThe analyses revealed significant associations between the use of media at bedtime and bedtime problems (in girls only), sleep behavior problems (in girls only), and daytime sleepiness (in girls and boys). Daily screen time, in contrast, was associated with none of the sleep difficulties. The number of media devices owned by the child was only associated with bedtime problems in girls, and this association lost statistical significance once media use at bedtime was included as further predictor.ConclusionThe findings underline the potentially sleep-disturbing role of electronic media at bedtime. Furthermore, they suggest that this effect is more pronounced in girls than in boys.
Relational vulnerability in motherhood—an existential perspective on pain and exhaustion among women
Authors: Gebhardt Anja J. , Andermo Susanne , Arman Maria 
Published: July 2024

IntroductionStress-related ill-health like pain and exhaustion are demanding public health problems in Europe. In Sweden, women are particularly at risk to develop stress-related ill-health during a period in life that coincides with child-rearing years. When entering motherhood, Swedish women’s sick leave substantially increases. Yet, motherhood is rarely acknowledged in clinical encounters concerning pain and exhaustion although women suffer from these ailments more often than men. To incorporate motherhood as an existential dimension of health in the care of women living with pain and exhaustion might alleviate women’s suffering. But knowledge on women’s experiences of motherhood and health is scarce. Therefore, the aim of the study is to reach a deeper understanding of how women suffering from long-lasting pain and exhaustion experience their health in relation to motherhood.MethodsRicoeur’s interpretation theory has been applied to analyze 27 phenomenological interviews with 14 mothers suffering from long-lasting pain and exhaustion.ResultsThese women’s experiences shed light on how closely motherhood is interwoven with the experience of their health and suffering: The women’s suffering seems to be rooted in a relational vulnerability that has been uncovered during motherhood. Further, the women suffer from a burden of difficult life experiences and inner conflicts. Reconciliation with life is possible when women find an existential shelter, which offers ways to relate to their suffering making the own suffering more bearable.