bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward institutional transformation: warming the chilly climate for women in STEM through macrostructural change
Authors: Erichsen Kristen , Šaras Emily D. , Perez-Felkner Lara
Published: April 2024

Introduction

Although the demand for graduates with Science, Technology, Engineering, and Mathematics (STEM) credentials continues to climb, women remain underrepresented as both students and faculty in STEM higher education. Compounding social forces can hinder organizational change for gender equity in STEM, constraining institutions and individuals within them. This study advances macrostructural theory to examine the impact of gender composition (including group size and heterogeneity) of women faculty on structural change, as measured by gender desegregation of STEM degree earners. We advance this theory by incorporating faculty rank, rather than treating group composition as a static category.

Method

This study draws on a federal repository of data to assess institutional change in the share of STEM women faculty in the U.S. We employ quasi-experimental methods to explore the following research questions: (1) does hiring more women onto an institution’s faculty roster shrink the gender gap among STEM degree earners? and (2) does segregation of faculty by gender within institutions shape the gender gap among STEM degree earners?

Findings

While institutional efforts herald their efforts of hiring more women faculty, our findings indicate that gender desegregation of STEM degree earners partially depends on the promotion of women faculty to tenure.

Discussion

Implications for theory, policy, and practice are discussed, with a focus on institutional-level change.
Associations between sex hormones, receptors, binding proteins and inflammatory bowel disease: a Mendelian randomization study
Authors: Zou Fei , Hu Yaxian , Xu Mengmeng , Wang Su , Wu Zengrong , Deng Feihong
Published: April 2024

Background

Gender differences existed in inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Observational studies have revealed associations between sex hormones and IBD, such as estrogen and testosterone. However, the exact relationship between these sex hormones and IBD is unclear.

Method

Based on the genome-wide association studies data of eight sex hormones, two sex hormone receptors, sex hormone-binding globulin (SHBG), total IBD and its two subtypes, we performed a two-sample Mendelian randomization (MR) study to analyze their mutual relationship. For estradiol (E2), progesterone (PROG), bioavailable testosterone (BAT), total testosterone (TT) and SHBG, sex-stratified MR analyses were also performed. Inverse variance weighted method, MR-Egger regression and Weighted median method were used for causal analyses. Sensitivity analyses were conducted to test the stability of causal relationships. Besides, a reverse MR analysis was performed to estimate the reverse causation.

Results

E2 (P=0.028) and TT (P=0.034) had protective effects on CD. Sex-stratified analyses revealed protective roles of E2 in males on total IBD (P=0.038) and CD (P=0.020). TT in females had protective effects on total IBD (P=0.025) and CD (P=0.029), and BAT in females decreased the risk of developing CD (P=0.047) and UC (P=0.036). Moreover, SHBG in males was also associated with a decreased risk of CD (P=0.021). The reversed MR analysis showed that CD was negatively correlated with estrogen receptor (P=0.046). UC was negatively correlated with PROG in females (P=0.015) and positively correlated with SHBG levels in males (P=0.046).

Conclusion

Findings of this study revealed the mutual causal associations between sex hormones and the risk of developing IBD.
RNA-seq analysis-based study on the effects of gestational diabetes mellitus on macrosomia
Authors: Gao Qianqian , Xu Guanying , Wang Guijie , Wang Wei , Zhu Chao , Shi Yang , Guo Changzhuang , Cong Jing , Ming Hongxia , Su Dongmei , Ma Xu
Published: April 2024

Background

Both the mother and the infant are negatively impacted by macrosomia. Macrosomia is three times as common in hyperglycemic mothers as in normal mothers. This study sought to determine why hyperglycemic mothers experienced higher macrosomia. Methods: Hematoxylin and Eosin staining was used to detect the placental structure of normal mother(NN), mothers who gave birth to macrosomia(NM), and mothers who gave birth to macrosomia and had hyperglycemia (DM). The gene expressions of different groups were detected by RNA-seq. The differentially expressed genes (DEGs) were screened with DESeq2 R software and verified by qRT-PCR. The STRING database was used to build protein-protein interaction networks of DEGs. The Cytoscape was used to screen the Hub genes of the different group.

Results

The NN group’s placental weight differed significantly from that of the other groups. The structure of NN group’s placenta is different from that of the other group, too. 614 and 3207 DEGs of NM and DM, respectively, were examined in comparison to the NN group. Additionally, 394 DEGs of DM were examined in comparison to NM. qRT-PCR verified the results of RNA-seq. Nucleolar stress appears to be an important factor in macrosomia, according on the results of KEGG and GO analyses. The results revealed 74 overlapped DEGs that acted as links between hyperglycemia and macrosomia, and 10 of these, known as Hub genes, were key players in this process. Additionally, this analysis believes that due of their close connections, non-overlapping Hubs shouldn’t be discounted.

Conclusion

In diabetic mother, ten Hub genes (RPL36, RPS29, RPL8 and so on) are key factors in the increased macrosomia in hyperglycemia. Hyperglycemia and macrosomia are linked by 74 overlapping DEGs. Additionally, this approach contends that non-overlapping Hubs shouldn’t be ignored because of their tight relationships.
Requirements on synthesis gas from gasification for material and energy utilization: a mini review
Authors: Leuter Philipp , Fendt Sebastian , Spliethoff Hartmut
Published: April 2024

Achieving sustainable energy and material use mandates a critical focus on carbon recycling. The imperative for an efficient carbon cycle is paramount in sustainable energy systems and the chemical industry. Syngas, derived from waste and biomass gasification, offers a robust foundation for such recycling efforts. Various technologies, each with unique gas purity requirements, facilitate further refinement of syngas. This study provides a detailed and comparative analysis of the purity specifications necessary for both energetic and material utilization pathways.
Autoimmune diseases and their genetic link to bronchiectasis: insights from a genetic correlation and Mendelian randomization study
Authors: Su Yue , Zhang Youqian , Chai Yanhua , Xu Jinfu
Published: April 2024

Background

Previous studies have demonstrated that autoimmune diseases are closely associated with bronchiectasis (BE). However, the causal effects between autoimmune diseases and BE remain elusive.

Methods

All summary-level data were obtained from large-scale Genome-Wide Association Studies (GWAS). The univariate Mendelian randomization (UVMR) was utilized to investigate the genetic causal correlation (rg) of 12 autoimmune diseases and bronchiectasis, The Multivariable Mendelian Randomization (MVMR) method was used to explore the effects of the confounding factors. Further investigation was conducted to identify potential intermediate factors using mediation analysis. Finally, the linkage disequilibrium score regression (LDSC) method was used to identify genetic correlations among complex traits. A series of sensitivity analyses was performed to validate the robustness of the results.

Results

The LDSC analysis revealed significant genetic correlations between BE and Crohn’s disease (CD) (rg = 0.220, P = 0.037), rheumatoid arthritis (RA) (rg = 0.210, P = 0.021), and ulcerative colitis (UC) (rg = 0.247, P = 0.023). However, no genetic correlation was found with other autoimmune diseases (P > 0.05). The results of the primary IVW analysis suggested that for every SD increase in RA, there was a 10.3% increase in the incidence of BE (odds ratio [OR] = 1.103, 95% confidence interval [CI] 1.055-1.154, P = 1.75×10-5, FDR = 5.25×10-5). Furthermore, for every standard deviation (SD) increase in celiac disease (CeD), the incidence of BE reduced by 5.1% (OR = 0.949, 95% CI 0.902-0.999, P = 0.044, FDR = 0.044). We also observed suggestive evidence corresponding to a 3% increase in BE incidence with T1DM (OR = 1.033, 95% CI 1.001-1.066, P = 0.042, FDR = 0.063). Furthermore, MVMR analysis showed that RA was an independent risk factor for BE, whereas mediator MR analysis did not identify any mediating factors. The sensitivity analyses corroborated the robustness of these findings.

Conclusion

LDSC analysis revealed significant genetic correlations between several autoimmune diseases and BE, and further MVMR analysis showed that RA is an independent risk factor for BE.
Interferon alpha promotes caspase-8 dependent ultraviolet light-mediated keratinocyte apoptosis via interferon regulatory factor 1
Authors: Loftus Shannon N. , Gharaee-Kermani Mehrnaz , Xu Bin , Moore Tyson M. , Hannoudi Andrew , Mallbris Mischa J. , Klein Benjamin , Gudjonsson Johann E. , Kahlenberg J. Michelle
Published: April 2024

Introduction

Ultraviolet (UV) light is a known trigger of both cutaneous and systemic disease manifestations in lupus patients. Lupus skin has elevated expression of type I interferons (IFNs) that promote increased keratinocyte (KC) death after UV exposure. The mechanisms by which KC cell death is increased by type I IFNs are unknown.

Methods

Here, we examine the specific cell death pathways that are activated in KCs by type I IFN priming and UVB exposure using a variety of pharmacological and genetic approaches. Mice that overexpress Ifnk in the epidermis were exposed to UVB light and cell death was measured. RNA-sequencing from IFN-treated KCs was analyzed to identify candidate genes for further analysis that could drive enhanced cell death responses after UVB exposure.

Results

We identify enhanced activation of caspase-8 dependent apoptosis, but not other cell death pathways, in type I IFN and UVB-exposed KCs. In vivo, overexpression of epidermal Ifnk resulted in increased apoptosis in murine skin after UVB treatment. This increase in KC apoptosis was not dependent on known death ligands but rather dependent on type I IFN-upregulation of interferon regulatory factor 1 (IRF1).

Discussion

These data suggest that enhanced sensitivity to UV light exhibited by lupus patients results from type I IFN priming of KCs that drives IRF1 expression resulting in caspase-8 activation and increased apoptosis after minimal exposures to UVB.
Overcoming the challenges encountered in CAR-T therapy: latest updates from the 2023 ASH annual conference
Authors: Zhang Tingting , Zhang Yicheng , Wei Jia
Published: April 2024

Chimeric antigen receptor (CAR) -T cell therapy has entered the breakthrough era, characterized by a blend of therapeutic opportunities and challenges. With the integration of genome-editing technology, CAR-T cells will be empowered to become super warriors in eradicating tumor cells and attacking various tumors, including T-cell malignancies and acute myeloid leukemia. Notably, the optimization of CAR-T cells, including efficacy, safety, and manufacturing speed, coupled with other therapeutic strategies such as radiotherapy, hematopoietic stem cell transplantation, small-molecule inhibitors, and bispecific antibodies, could revolutionize the therapeutic landscape of tumors. Consequently, next-generation cellular immunotherapy, including universal CAR-NK cells and synergistic combination approaches, are anticipated to significantly impact cancer treatment in the coming decade. Nevertheless, the failure rates of CAR-T therapy continue to be significant. The challenge lies in determining the optimal combination strategy and identifying reliable and robust biomarkers to effectively select the patients who will derive the greatest benefit from CAR-T therapy. Herein, we highlight recent innovations in CAR-T products, combination strategies and predictive biomarkers of response presented at the 2023 ASH Annual Meeting.
Sounding out horse mussel sediment thickness: an integrated data approach
Authors: Sheehy Jack , Bates Richard , Bell Michael , Porter Jo
Published: April 2024

Horse mussel beds are listed as a Priority Marine Feature (PMF) in Scotland for their influence in the creation of diverse benthic communities and provision of ecosystem services. In Scotland, horse mussel beds are also recognised for their importance in marine carbon sequestration. Unfortunately, there is a paucity of data on horse mussel bed carbon stocks and sediment thickness. There are also significant financial and logistical barriers with which to address these data gaps. This study investigates the robustness of Sub-Bottom Profiling (SBP) as a cost-effective method to quantify horse mussel sediment thickness across a landscape. Integrating SBP and Drop-Down Video (DDV) data, this study also details an integrated approach to investigate the links between horse mussel habitat condition and sediment thickness. With the addition of abiotic data, this study uses Structural Equation Modelling (SEM) to elucidate key relationships between abiotic factors, biotic variables, and sediment thickness. There is a significant positive correlation of horse mussel habitat condition and sediment thickness. Average horse mussel total sediment thickness, across all measures of habitat condition, was 1.37m. These findings substantially increase previous estimates of horse mussel sediment thickness, and potential value to climate change mitigation through blue carbon frameworks. This study highlights the importance of both abiotic and biotic factors on marine carbon sediment quantification.
Improvement of thermostability and catalytic efficiency of xylanase from Myceliophthora thermophilar by N-terminal and C-terminal truncation
Authors: Yang Yue , Zhang Chengnan , Lu Hongyun , Wu QiuHua , Wu Yanfang , Li Weiwei , Li Xiuting
Published: April 2024

Introduction

Extracting xylanase from thermophilic filamentous fungi is a feasible way to obtain xylanase with good thermal stability.

Methods

The transcriptomic data of Myceliophthora thermophilic destructive ATCC42464 were differentially expressed and enriched. By comparing the sequences of Mtxylan2 and more than 10 xylanases, the N-terminal and C-terminal of Mtxylan2 were truncated, and three mutants 28N, 28C and 28NC were constructed.

Results and discussion

GH11 xylan Mtxylan2 was identified by transcriptomic analysis, the specific enzyme activity of Mtxylan2 was 104.67 U/mg, and the optimal temperature was 65°C. Molecular modification of Mtxylan2 showed that the catalytic activity of the mutants was enhanced. Among them, the catalytic activity of 28C was increased by 9.3 times, the optimal temperature was increased by 5°C, and the residual enzyme activity remained above 80% after 30 min at 50–65°C, indicating that redundant C-terminal truncation can improve the thermal stability and catalytic performance of GH11 xylanase.
Differential degradation of petroleum hydrocarbons by Shewanella putrefaciens under aerobic and anaerobic conditions
Authors: Li Yang , Liu Yuan , Guo Dongyi , Dong Hailiang
Published: April 2024

The complexity of crude oil composition, combined with the fluctuating oxygen level in contaminated environments, poses challenges for the bioremediation of oil pollutants, because of compound-specific microbial degradation of petroleum hydrocarbons under certain conditions. As a result, facultative bacteria capable of breaking down petroleum hydrocarbons under both aerobic and anaerobic conditions are presumably effective, however, this hypothesis has not been directly tested. In the current investigation, Shewanella putrefaciens CN32, a facultative anaerobic bacterium, was used to degrade petroleum hydrocarbons aerobically (using O2 as an electron acceptor) and anaerobically (using Fe(III) as an electron acceptor). Under aerobic conditions, CN32 degraded more saturates (65.65 ± 0.01%) than aromatics (43.86 ± 0.03%), with the following order of degradation: dibenzofurans > n-alkanes > biphenyls > fluorenes > naphthalenes > alkylcyclohexanes > dibenzothiophenes > phenanthrenes. In contrast, under anaerobic conditions, CN32 exhibited a higher degradation of aromatics (53.94 ± 0.02%) than saturates (23.36 ± 0.01%), with the following order of degradation: dibenzofurans > fluorenes > biphenyls > naphthalenes > dibenzothiophenes > phenanthrenes > n-alkanes > alkylcyclohexanes. The upregulation of 4-hydroxy-3-polyprenylbenzoate decarboxylase (ubiD), which plays a crucial role in breaking down resistant aromatic compounds, was correlated with the anaerobic degradation of aromatics. At the molecular level, CN32 exhibited a higher efficiency in degrading n-alkanes with low and high carbon numbers relative to those with medium carbon chain lengths. In addition, the degradation of polycyclic aromatic hydrocarbons (PAHs) under both aerobic and anaerobic conditions became increasingly difficult with increased numbers of benzene rings and methyl groups. This study offers a potential solution for the development of targeted remediation of pollutants under oscillating redox conditions.
The increased effective connectivity from left middle occipital gyrus to right medial septum/diagonal bands in AD patients after donepezil intervention
Authors: Yang Ting , Wei Fuquan , Guo Yufei , Zhu Mengxiao , Hou Hongtao , Guo Zhongwei , Liu Xiaozheng
Published: April 2024

Introduction

Donepezil enhances the function of cholinergic nerves by increasing the concentration of acetylcholine, thereby improving clinical symptoms in patients with Alzheimer’s disease (AD). However, the neural mechanisms of how donepezil modulates the effective connectivity (EC) network of cholinergic system in AD patients remain unknown. We speculated that the effective network of the cholinergic system changes in AD patients after donepezil intervention.

Methods

We employed resting-state functional magnetic resonance imaging and Granger causality analysis approach to explore changes in the effective connectivity network of the basal forebrain in AD patients before and after donepezil intervention. This study included 32 participants, including 16 healthy controls (HCs) and 16 AD patients. In a 3T MRI scanner, the 16 AD patients were scanned before and after the donepezil intervention. To compare EC differences between the three groups of participants, ANOVA and post-hoc t-tests analysis were employed.

Results

Compared to baseline status, AD patients after donepezil intervention had an increased EC from left middle occipital gyrus to right medial septum/diagonal bands. Compared to HCs, AD patients after donepezil intervention had an increased EC from right inferior frontal gyrus/orbit part to right medial septum/diagonal bands, AD patients before donepezil intervention had a reduced EC from right precuneus to right medial septum/diagonal bands. A significant positive correlation was found between EC values in right precuneus and Mini-Mental State Examination in pre-intervention AD patients (r = 0.7338, p = 0.0012).

Discussion

Our study showed that effective connectivity of brain regions associated with the default mode network in the cholinergic pathway was enhanced after donepezil intervention. The results of this study will help us to better understand the neural mechanisms of donepezil intervention in AD and to find clinical targets for intervention.
A proof of concept: digital diary using 24-hour monitoring using wearable device for patients with Parkinson’s disease in nursing homes
Authors: Kamo Hikaru , Oyama Genko , Yamasaki Yui , Nagayama Tomohiro , Nawashiro Ryotatsu , Hattori Nobutaka
Published: April 2024

Introduction

In the advanced stages of Parkinson’s disease (PD), motor complications such as wearing-off and dyskinesia are problematic and vary daily. These symptoms need to be monitored precisely to provide adequate care for patients with advanced PD.

Methods

This study used wearable devices to explore biomarkers for motor complications by measuring multiple biomarkers in patients with PD residing in facilities and combining them with lifestyle and clinical assessments. Data on the pulse rate and activity index (metabolic equivalents) were collected from 12 patients over 30 days.

Results

The pulse rate and activity index during the off- and on-periods and dyskinesia were analyzed for two participants; the pulse rate and activity index did not show any particular trend in each participant; however, the pulse rate/activity index was significantly greater in the off-state compared to that in the dyskinesia and on-states, and this index in the dyskinesia state was significantly greater than that in the on-state in both participants.

Conclusion

These results suggest the pulse rate and activity index combination would be a useful indicator of wearing-off and dyskinesia and that biometric information from wearable devices may function as a digital diary. Accumulating more cases and collecting additional data are necessary to verify our findings.
Color discrimination in fixed saturation level of patients with acute traumatic injury
Authors: Nicolau da Costa Leonardo R. , Sousa Joyce B. , Brito Felipe André C. , Igarashi Yuzo , Gomes Janildes Maria Silva , Lobão Carlos Augusto , Costa Marcelo Fernandes , Miquilini Leticia , Souza Givago Silva
Published: April 2024

Introduction

Traumatic brain injury (TBI) is an important public health concern and that may lead to severe neural sequels, such as color vision deficits.

Methods

We evaluated the color vision of 10 TBI patients with normal cognitive function using a color discrimination test in a fixed saturation level. We also analyzed computerized tomography scans to identify the local of the brain damages.

Results

Four TBI patients that had lesions in brain areas of the ventral visual streams, five TBI patients had lesions inferred in brain areas of the dorsal visual stream, and one TBI patient had lesion in the occipital area. All the patients had cognitive and color vision screened and they had characterized the chromatic discrimination at high and low saturation. All participants had no significant cognitive impairment in the moment of the color vision test. Additionally, they had perfect performance for discrimination of chromatic stimulus at high saturation and similar to controls (n = 37 age-matched participants). Three of four TBI patients with lesions in the ventral brain and one patient with lesion in the occipital area had impairment of the chromatic discrimination at low saturation. All TBI patients with lesions in the dorsal brain had performance similar or slightly worse than the controls.

Conclusion

Chromatic discrimination at low saturation was associated to visual damage in the ventral region of the brain and is a potential tool for functional evaluation of brain damage in TBI patients.
A prospective observational study comparing outcomes application of low-frequency pulse electrical combined with target-oriented rehabilitation therapy in postoperative nerve function rehabilitation of patients with distal humeral fracture and radial nerve injury
Authors: Shi Shaoyan , Ou Xuehai , Du Xiaolong
Published: April 2024

Objective

The aim of the present study was to compare the effect of low-frequency pulse electrical stimulation combined with target-oriented rehabilitation therapy and single low-frequency pulse electrical stimulation therapy on postoperative neurological improvement in patients with radial nerve injury and humeral condylar fracture.

Methods

A total of 88 patients with humeral condyle fracture and radial nerve injury admitted to our hospital from April 2019 to January 2022 were randomly divided into a combined group and a control group, with 44 patients in each group. The patients in the combined group received low-frequency pulse electrical stimulation combined with target-oriented rehabilitation therapy, while those in the control group received low-frequency pulse electrical stimulation therapy. The recovery rate of radial nerve function, the recovery of finger extensor and wrist extensor muscle strength, and the occurrence of postoperative complications were evaluated in all patients.

Results

After treatment, the recovery rate in the combined group (77.27%) was higher than that in the control group (50.00%) (p < 0.05). There was no significant difference in finger extensor and wrist extensor muscle strength before treatment between the two groups (p > 0.05). After treatment, both groups showed improvement compared to before treatment (p < 0.05), and the recovery in the combined group was better than that in the control group (p < 0.05). There was no significant difference in MCV and amplitude before treatment between the two groups (p > 0.05). After treatment, both groups showed improvement compared to before treatment (p < 0.05), and the recovery in the combined group was better than that in the control group (p < 0.05). The fracture healing time in the combined group was shorter than that in the control group (p < 0.05). During the treatment period, there was one case of infection and one case of joint pain in the combined group, with a complication rate of 4.55%. In the control group, there was one case of infection and two cases of joint pain, with a complication rate of 6.82%. There was no significant difference in the complication rate between the two groups (p > 0.05). The DHI score in the combined group was better than that in the control group (p < 0.05). The ESCA score in the combined group was better than that in the control group (p < 0.05).

Conclusion

Low-frequency pulse electrical stimulation combined with target-oriented rehabilitation therapy can promote muscle strength and functional recovery after radial nerve injury, accelerate fracture healing time, and no additional risk of complications.

Clinical trial registration

https://www.researchregistry.com/, researchregistry9461.
Decoding visual fatigue in a visual search task selectively manipulated via myopia-correcting lenses
Authors: Ryu Hyeongsuk , Ju Uijong , Wallraven Christian
Published: April 2024

Introduction

Visual fatigue resulting from sustained, high-workload visual activities can significantly impact task performance and general wellbeing. So far, however, little is known about the underlying brain networks of visual fatigue. This study aimed to identify such potential networks using a unique paradigm involving myopia-correcting lenses known to directly modulate subjectively-perceived fatigue levels.

Methods

A sample of N = 31 myopia participants [right eye-SE: –3.77D (SD: 2.46); left eye-SE: –3.75D (SD: 2.45)] performed a demanding visual search task with varying difficulty levels, both with and without the lenses, while undergoing fMRI scanning. There were a total of 20 trials, after each of which participants rated the perceived difficulty and their subjective visual fatigue level. We used representational similarity analysis to decode brain regions associated with fatigue and difficulty, analyzing their individual and joint decoding pattern.

Results and discussion

Behavioral results showed correlations between fatigue and difficulty ratings and above all a significant reduction in fatigue levels when wearing the lenses. Imaging results implicated the cuneus, lingual gyrus, middle occipital gyrus (MOG), and declive for joint fatigue and difficulty decoding. Parts of the lingual gyrus were able to selectively decode perceived difficulty. Importantly, a broader network of visual and higher-level association areas showed exclusive decodability of fatigue (culmen, middle temporal gyrus (MTG), parahippocampal gyrus, precentral gyrus, and precuneus). Our findings enhance our understanding of processing within the context of visual search, attention, and mental workload and for the first time demonstrate that it is possible to decode subjectively-perceived visual fatigue during a challenging task from imaging data. Furthermore, the study underscores the potential of myopia-correcting lenses in investigating and modulating fatigue.
Expression characteristics and potential function of non-coding RNA in mouse cortical cells
Authors: Wei Yanrong , Lei Junjie , Peng Yujie , Chang Huizhong , Luo Ting , Tang Yuanchun , Wang Lifang , Wen Huiying , Volpe Giacomo , Liu Longqi , Han Lei
Published: April 2024

Non-coding RNAs (ncRNAs) play essential regulatory functions in various physiological and pathological processes in the brain. To systematically characterize the ncRNA profile in cortical cells, we downloaded single-cell SMART-Seq v4 data of mouse cerebral cortex. Our results revealed that the ncRNAs alone are sufficient to define the identity of most cortical cell types. We identified 1,600 ncRNAs that exhibited cell type specificity, even yielding to distinguish microglia from perivascular macrophages with ncRNA. Moreover, we characterized cortical layer and region specific ncRNAs, in line with the results by spatial transcriptome (ST) data. By constructing a co-expression network of ncRNAs and protein-coding genes, we predicted the function of ncRNAs. By integrating with genome-wide association studies data, we established associations between cell type-specific ncRNAs and traits related to neurological disorders. Collectively, our study identified differentially expressed ncRNAs at multiple levels and provided the valuable resource to explore the functions and dysfunctions of ncRNAs in cortical cells.
Construction and validation of a nomogram for predicting overall survival of patients with stage III/IV early−onset colorectal cancer
Authors: Yin Wanbin , Pei Wenju , Yu Tao , Zhang Qi , Zhang Shiyao , Zhang Maorun , Liu Gang
Published: April 2024

Purpose

This study aimed to identify prognostic factors and develop a nomogram for predicting overall survival (OS) in stage III/IV early-onset colorectal cancer (EO-CRC).

Methods

Stage III/IV EO-CRC patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The datasets were randomly divided (2:1) into training and validation sets. A nomogram predicting OS was developed based on the prognostic factors identified by Cox regression analysis in the training cohort. Moreover, the predictive performance of the nomogram was assessed using the receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Subsequently, the internal validation was performed using the validation cohort. Finally, a risk stratification system was established based on the constructed nomogram.

Results

Of the 10,387 patients diagnosed with stage III/IV EO-CRC between 2010 and 2015 in the SEER database, 8,130 patients were included. In the training cohort (n=3,071), sex, marital status, race/ethnicity, primary site, histologic subtypes, grade, T stage, and N stage were identified as independent prognostic variables for OS. The 1-, 3-, and 5-year area under the curve (AUC) values of the nomogram were robust in both the training (0.751, 0.739, and 0.723) and validation cohorts (0.748, 0.733, and 0.720). ROC, calibration plots, and DCA indicated good predictive performance of the nomogram in both the training and validation sets. Furthermore, patients were categorized into low-, middle-, and high-risk groups based on the nomogram risk score. Kaplan-Meier curve showed significant survival differences between the three groups.

Conclusion

We developed a prognostic nomogram and risk stratification system for stage III/IV EO-CRC, which may facilitate clinical decision-making and individual prognosis prediction.
Comparison of robot-assisted single-port-plus-one pyeloplasty vs. laparoscopic single-port pyeloplasty in the treatment of ureteropelvic junction obstruction in children
Authors: Li Jun , Chen Jingyi , Jia Jinfu , He Shaohua , Xu Di
Published: April 2024

Objective

To compare the efficacy of robot-assisted single-port-plus-one pyeloplasty (RSPY) and laparoscopic single-port pyeloplasty (LSPY) in the treatment of children with ureteropelvic junction obstruction (UPJO).

Methods

The clinical data of 47 children who underwent surgery for UPJO at the Department of the Pediatric Surgery of the Fujian Provincial Hospital from October 2020 to September 2022 were analyzed retrospectively. Of these 47 children, 27 received RSPY while 20 underwent LSPY. The baseline data, operation time, intraoperative anastomosis time, intraoperative blood loss, postoperative hospital stay, complications, total cost, preoperative and postoperative renal parenchymal thickness (PT), anteroposterior renal pelvis diameter (APD), and differential renal function (DRF) of the two groups were compared to evaluate the clinical efficacy of the two surgical methods.

Results

The results showed that both surgical techniques were successful and no patient transitioned to open surgery. There was no significant difference between the two groups in baseline data, intraoperative blood loss, complications, APD, and PT 6 months after surgery. There was also no significant difference in APD, PT, and DRF 12 months after surgery (all P > 0.05). Compared with the LSPY group, the RSPY group had shorter operation time [(153.04 ± 14.44) vs. (189.90 ± 32.59) min, t = −5.24, P < 0.05], less intraoperative anastomosis time [(68.81 ± 16.80) vs. (97.45 ± 11.99) min, t = −6.49, P < 0.05], shorter postoperative hospital stay [(5.96 ± 1.34) vs. (9.00 ± 1.33) d, t = −7.68, P < 0.05], but higher total cost [(57,390 ± 7,664) vs. (30,183 ± 4,219) yuan, t = 14.32, P < 0.05].

Conclusion

Compared with LSPY, RSPY achieves equivalent efficacy in the treatment of UPJO in children and has certain advantages by shortening the operation time, intraoperative anastomosis time, and postoperative hospital stay. However, its cost burden is heavy, and appropriate cases need to be selected for popularization and application.
Case Report: Perianal infection in children caused by ingested jujube pits: a report of two cases
Authors: Jiang Guoping , Wu Lixu , Ruan Weiwei , Shao Qian , Zhu JianMing
Published: April 2024

Background

The ingestion of jujube pits by children is a rare cause of perianal infection.This article aimed to report two cases of perianal infection in children resulting from the ingestion of jujube pits.

Methods

We reviewed the clinical records of perianal infection caused by jujube pits at our hospital. Details of the patients’ presentation, imaging studies, complications and treatment were recorded.

Results

Both pediatric patients presented with perianal swelling and pain. The caregivers of both patients denied a history of jujube consumption. Magnetic resonance imaging (MRI) indicated the presence of jujube pits, which were subsequently removed during surgery. Postoperatively, both patients recovered well, and follow-up showed no recurrence or the formation of anal fistulas.

Conclusion

The ingestion of jujube pits leading to perianal infection is rare and inconspicuous. Early diagnosis and treatment are beneficial in preventing the occurrence of serious complications.
The potential of astragalus polysaccharide for treating diabetes and its action mechanism
Authors: Liu Shiyu , Wang Luyao , Zhang Zehua , Leng YuLin , Yang Yan , Fu Xiaoxu , Xie Hongyan , Gao Hong , Xie Chunguang
Published: April 2024

Type 2 diabetes presents a significant global health burden and is frequently linked to serious clinical complications, including diabetic cardiomyopathy, nephropathy, and retinopathy. Astragalus polysaccharide (APS), extracted from Astragalus membranaceus, exhibits various biochemical and physiological effects. In recent years, a growing number of researchers have investigated the role of APS in glucose control and the treatment of diabetes and its complications in various diabetes models, positioning APS as a promising candidate for diabetes therapy. This review surveys the literature on APS from several databases over the past 20 years, detailing its mechanisms of action in preventing and treating diabetes mellitus. The findings indicate that APS can address diabetes by enhancing insulin resistance, modulating the immune system, protecting islet cells, and improving the intestinal microbiota. APS demonstrates positive pharmacological value and clinical potential in managing diabetic complications, including diabetic retinopathy, nephropathy, cardiomyopathy, cognitive dysfunction, wound healing, and more. However, further research is necessary to explore APS’s bioavailability, optimal dosage, and additional clinical evidence.
Bactericidal and biofilm eradication efficacy of a fluorinated benzimidazole derivative, TFBZ, against methicillin-resistant Staphylococcus aureus
Authors: Chen Qian , Dong Zhihui , Yao Xuedi , Sun Huan , Pan Xin , Liu Jikai , Huang Rong
Published: April 2024

Methicillin-resistant Staphylococcus aureus (MRSA) is a major inducement of nosocomial infections and its biofilm formation render the high tolerance to conventional antibiotics, which highlights the requirement to develop new antimicrobial agents urgently. In this study, we identified a fluorinated benzimidazole derivative, TFBZ, with potent antibacterial efficacy toward planktonic MRSA (MIC = 4 μg/mL, MBC = 8 μg/mL) and its persistent biofilms (≥99%, MBEC = 8 μg/mL). TFBZ manifested significant irreversible time-dependent killing against MRSA as characterized by diminished cell viability, bacterial morphological change and protein leakage. Furthermore, the results from CBD devices, crystal violet assay in conjunction with live/dead staining and scanning electron microscopy confirmed that TFBZ was capable of eradicating preformed MRSA biofilms with high efficiency. Simultaneously, TFBZ reduced the bacterial invasiveness and exerted negligible hemolysis and cytotoxicity toward mammalian cells, which ensuring the robust therapeutic effect on mouse skin abscess model. The transcriptome profiling and quantitative RT-PCR revealed that a set of encoding genes associated with cell adhesion, biofilm formation, translation process, cell wall biosynthesis was consistently downregulated in MRSA biofilms upon exposure to TFBZ. In conclusion, TFBZ holds promise as a valuable candidate for therapeutic applications against MRSA chronic infections.
Physalin H, physalin B, and isophysalin B suppress the quorum-sensing function of Staphylococcus aureus by binding to AgrA
Authors: Yamaguchi Junpei , Manome Teruhisa , Hara Yasumasa , Yamazaki Yuriko , Nakamura Yuumi , Ishibashi Masami , Takaya Akiko
Published: April 2024

The virulence of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), depends on the expression of toxins and virulence factors controlled by the quorum-sensing (QS) system, encoded on the virulence accessory gene regulator (agr) locus. The aim of this study was to identify a phytochemical that inhibits Agr-QS function and to elucidate its mechanism. We screened 577 compounds and identified physalin H, physalin B, and isophysalin B—–phytochemicals belonging to physalins found in plants of the Solanaceae family—–as novel Agr-QS modulators. Biological analyses and in vitro protein–DNA binding assays suggested that these physalins suppress gene expression related to the Agr-QS system by inhibiting binding of the key response regulator AgrA to the agr promoters, reducing the function of hemolytic toxins downstream of these genes in MRSA. Furthermore, although physalin F suppressed gene expression in the Agr-QS system, its anti-hemolytic activity was lower than that of physalins H, B, and isophysalin B. Conversely, five physalins isolated from the same plant with the ability to suppress Agr-QS did not reduce bacterial Agr-QS activity but inhibited AgrA binding to DNA in vitro. A docking simulation revealed that physalin interacts with the DNA-binding site of AgrA in three docking states. The carbonyl oxygens at C-1 and C-18 of physalins, which can suppress Agr-QS, were directed to residues N201 and R198 of AgrA, respectively, whereas these carbonyl oxygens of physalins, without Agr-QS suppression activity, were oriented in different directions. Next, 100-ns molecular dynamics simulations revealed that the hydrogen bond formed between the carbonyl oxygen at C-15 of physalins and L186 of AgrA functions as an anchor, sustaining the interaction between the carbonyl oxygen at C-1 of physalins and N201 of AgrA. Thus, these results suggest that physalin H, physalin B, and isophysalin B inhibit the interaction of AgrA with the agr promoters by binding to the DNA-binding site of AgrA, suppressing the Agr-QS function of S. aureus. Physalins that suppress the Agr-QS function are proposed as potential lead compounds in the anti-virulence strategy for MRSA infections.
Implementing the EU HTA regulation: Insights from semi-structured interviews on patient expectations, Belgian and European institutional perspectives, and industry outlooks
Authors: Desmet Thomas , Brijs Maud , Vanderdonck Frank , Tops Sven , Simoens Steven , Huys Isabelle
Published: April 2024

Introduction: The goal of the Health Technology Assessment (HTA) Regulation 2021/2282 is to establish a more harmonized HTA framework, fostering member states cooperation and enabling equal patient access to innovative health technologies in Europe. This research aimed to assess the impact of the regulation on national HTAs, the strategic implications for health technology developers, and its influence on price and reimbursement negotiations.

Methods: A scoping literature review encompassing peer-reviewed literature as well as grey literature was conducted. Between February and March 2023, semi-structured interviews (n = 20) were performed with stakeholders from Belgian governmental institutions, European institutions, advanced therapy medicinal product developers, academics, and sickness funds. The interviews were analyzed using the framework analysis method.

Results: Numerous steps, such as the development of implementing acts and procedural guidelines remain to be taken. At member state level, national/regional HTA bodies and payers must act to adopt the new concepts of Joint Scientific Consultations (JSC) and Joint Clinical Assessments (JCA) within their national legislation, as well as revise their timelines and prepare for interactions at a European level. Compiling a harmonized PICO (Population, Intervention, Comparator, and Outcome), adapting local procedures, and increasing capacity to actively take part in the JSC and JCA are seen as primary barriers by several stakeholders. Training and education will help HTA bodies, payers, and health technology developers to participate in the European processes.

Conclusion: While practical and legal challenges were identified, recommendations (such as actively preparing for the upcoming changes and increasing capacity while providing training) were provided to adapt national and European procedures to the needs of the HTA Regulation 2021/2282. The importance of fostering collaborations and aligning local HTA procedures with the new way of working set out by the Regulation was demonstrated with this study.
Research status of rare-earth-ion-doped infrared laser
Authors: Zhang Jing-Xiang , Wang Gong , Li Yun-Fei , Yu Yu , Wang Yulei , Lv Zhiwei
Published: April 2024

Infrared lasers have an extensive range of applications in sensing, detection, communication, medicine, and other fields. The principle of directly pumping solid-state lasers is simple, and it can easily achieve high-power and high-efficiency laser output, which is one of the important means to obtain infrared lasers. Incorporating rare earth ions into the substrate as the gain medium for directly pumping solid-state lasers can alter their optical performance and further enhance the performance of the laser. Lasers based on rare earth ion doping have a small volume, high conversion efficiency, good beam quality, wide tuning range, and multiple operating modes. Therefore, the proportion of rare earth ions doped as the gain medium for activating ions is currently very large. In this review, Ho3+, Tm3+, and Er3+ are selected as the representative rare earth ions, and their optical properties, such as luminous power and fluorescence lifetime, when doped in different substrates, such as crystals, ceramics, and fibers, are introduced, respectively, to illustrate their feasibility as infrared laser gain media. In addition, we show the different optical properties when doped with two ions, three ions, and four ions, demonstrating their great potential as infrared laser gain media.
Titin: roles in cardiac function and diseases
Authors: Stroik Dawson , Gregorich Zachery R. , Raza Farhan , Ge Ying , Guo Wei
Published: April 2024

The giant protein titin is an essential component of muscle sarcomeres. A single titin molecule spans half a sarcomere and mediates diverse functions along its length by virtue of its unique domains. The A-band of titin functions as a molecular blueprint that defines the length of the thick filaments, the I-band constitutes a molecular spring that determines cell-based passive stiffness, and various domains, including the Z-disk, I-band, and M-line, serve as scaffolds for stretch-sensing signaling pathways that mediate mechanotransduction. This review aims to discuss recent insights into titin’s functional roles and their relationship to cardiac function. The role of titin in heart diseases, such as dilated cardiomyopathy and heart failure with preserved ejection fraction, as well as its potential as a therapeutic target, is also discussed.
Use of an automatic fruit-zone cooling system to cope with multiple summer stresses in Sangiovese and Montepulciano grapes
Authors: Valentini Gabriele , Allegro Gianluca , Pastore Chiara , Sangiorgio Daniela , Noferini Massimo , Muzzi Enrico , Filippetti Ilaria
Published: April 2024

Grapevines are frequently subjected to heatwaves and limited water availability during ripening. These conditions can have consequences for the physiological health of the vines. Moreover, the situation is often exacerbated by intense solar radiation, resulting in reduced yield due to sunburn and a decline in quality. In light of these challenges, our study aimed to develop a fruit-zone cooling system designed to mitigate grape sunburn damage and improve the microclimate conditions within the vineyard. The system comprises a network of proximal sensors that collect microclimate data from the vineyard and an actuator that activates nebulizers when the temperature exceeds the threshold of 35°C. The research was conducted over two years (2022 and 2023) in Bologna (Italy) using potted Sangiovese and Montepulciano vines. These two vintages were characterized by high temperatures, with varying amounts of rainfall during the test period, significantly impacting the evaporative demand, which was notably higher in 2023. Starting from the veraison stage we compared three treatments: Irrigated control vines (WW); Control vines subjected to 50% water restriction during the month of August (WS); WS vines treated with nebulized water in the bunch area during the stress period (WS+FOG). The application of nebulized water effectively reduced the temperature of both the air around the clusters and the clusters themselves. As we expected, Montepulciano showed better single leaf assimilation rate and stomatal conductance under non-limiting water conditions than Sangiovese while their behavior was unaffected under water-scarce conditions. Importantly, for the first time, we demonstrated that nebulized water positively affected gas exchange in both grape varieties. In addition to this, the vines treated with the misting system exhibited higher productivity compared to WS vines without affecting technological maturity. In the 2023 vintage, the activation of the system prevented the ripening blockage that occurred in Montepulciano under water stress. Regarding the concentration of total anthocyanins, a significant increase in color was observed in WS+FOG treatment, suggesting a predominant role of microclimate on anthocyanin biosynthesis and reduction of oxidative phenomena. In conclusion, the fruit-zone cooling system proved to be an invaluable tool for mitigating the adverse effects of multiple summer stresses.