bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomic Analysis Reveals Endometrial Dynamics in Normoweight and Overweight/Obese Polycystic Ovary Syndrome Women
Authors: Liu Su , Hong Ling , Lian Ruochun , Xiao Shan , Li Yuye , Diao Lianghui , Zeng Yong
Published: May 2022

The aim of this work was to identify the transcriptomic characteristics of the endometrium in normoweight and overweight/obese polycystic ovary syndrome (PCOS) potentially underlying the pathogenesis. This study included 38 patients undergoing in vitro fertilization: 22 women with PCOS and 16 matched controls. Each of the groups was subdivided into normoweight (body mass index (BMI) < 25 kg/m2) and overweight/obese (BMI ≥25 kg/m2) subgroups. Endometrium samples were collected in the secretory phase from controls or in a modeled secretory phase using daily administration of progesterone from women with PCOS before in vitro fertilization treatment. Transcriptome profiles were assessed by high-throughput RNA sequencing to investigate distinct endometrial gene expression patterns in PCOS. Bioinformatics analyses revealed that the endometrium from PCOS expresses significantly different transcripts encoding endometrial receptivity, inflammatory response, angiogenesis, and energy metabolism. Additionally, our study demonstrated that the differentially expressed genes between normoweight and overweight/obese PCOS are involved in fatty acid metabolism, endometrial decidualization, and immune response. For the first time, we have described the transcriptome characteristics of normoweight and overweight/obese PCOS endometria. Our results indicate different endometrial gene expressions between different subtypes of PCOS and non-PCOS women, which might affect endometrial functions in PCOS patients.
Identifying and Exploring the Candidate Susceptibility Genes of Cirrhosis Using the Multi-Tissue Transcriptome-Wide Association Study
Authors: Zhu Xiao-Bo , Hou Yu-Qing , Ye Xiang-Yu , Zou Yi-Xin , Xia Xue-Shan , Yang Sheng , Huang Peng , Yu Rong-Bin
Published: May 2022

Objective: We identify and explore the candidate susceptibility genes for cirrhosis and their underlying biological mechanism.

Methods: We downloaded the genome-wide association studies summary data of 901 cirrhosis cases and 451,363 controls and integrated them with reference models of five potential tissues from the Genotype-Tissue Expression (GTEx) Project, including whole blood, liver, pancreas, spleen, and thyroid, to identify genes whose expression is predicted to be associated with cirrhosis. Then, we downloaded gene expression data of individuals with hepatocellular carcinoma from TCGA database to conduct differential expression analysis to validate these identified genes and explored their possible role in driving cirrhosis via functional enrichment and gene set enrichment analysis (GSEA).

Results: We identified 10 significant genes (SKIV2L, JPH4, UQCC2, RP11-91I8.3, MAU2, ERAP1, PUS3, ZNF677, ARHGAP40, and SHANK3) associated with cirrhosis at a Bonferroni-corrected threshold of p < 0.01, among which two (SKIV2L and JPH4) were identified in the liver and five (SKIV2L, JPH4, MAU2, SHANK3, and UQCC2) were validated by differential expression analysis at an FDR-corrected threshold of p < 0.01. The enrichment analysis showed that the degradation process of RNA, which is enriched by 58 genes, is significantly under-enriched in liver cancer tissues (p = 0.0268).

Conclusion: We have identified several candidate genes for cirrhosis in multiple tissues and performed differential genetic analysis using the liver cancer database to verify the significant genes. We found that the genes SKIV2L and JPH4 identified in the liver are of particular concern. Finally, through enrichment analysis, we speculate that the process of mRNA transcription and RNA degradation may play a role in cirrhosis.
Identification of IL-6 Signalling Components as Predictors of Severity and Outcome in COVID-19
Authors: Rodríguez-Hernández María Ángeles , Carneros David , Núñez-Núñez María , Coca Ramón , Baena Rosario , López-Ruiz Gema M. , Cano-Serrano María Elena , Martínez-Tellería Alberto , Fuentes-López Ana , Praena-Fernandez Juan Manuel , Garbers Christoph , Hernández-Quero José , García Federico , Rose-John Stefan , Bustos Matilde
Published: May 2022

IL-6 is one of the major mediators of the hyper-inflammatory responses with complex biological functions as it can signalviadifferent modes of action. IL-6 by classical signalling has anti-inflammatory and antibacterial activities, while trans-signalling mediates pro-inflammatory effects. The net biological effect of IL-6 is established by multiple factors beyond its absolute concentration. Here, we assess the relationship between IL-6 signalling variables [IL-6, soluble IL-6R (sIL-6R) and soluble gp130 (sgp130)] and outcomes in a cohort of 366 COVID-19 patients. The potential trans-signalling was evaluated by a ratio between the pro-inflammatory binary IL-6:sIL-6R complex and the inactive ternary IL-6:sIL-6R:sgp130 complex (binary/ternary complex) and the fold molar excess of sgp130 over sIL-6R (FME). Our data provide new evidence that high levels of IL-6, sIL-6R, sgp130, binary/ternary complex ratio, and low FME are independent predictors of COVID-19 severity in survivor patients (without death), and the combination of IL-6 + sIL-6R + sgp130 exhibited the most robust classification capacity. Conversely, in a subgroup of patients with a very poor prognosis, we found that high levels of IL-6 and low levels of sIL-6R, sgp130, and binary/ternary complex ratio were predictors of death. In this context, the highest predictive capacity corresponded to the combined analysis of IL-6 + FME + lymphopenia + creatinine. Herein, we present IL-6 signalling variables as a helpful tool for the early identification and stratification of patients with clear implications for treatment and clinical decision-making.
Treatment of Tuberculosis and the Drug Interactions Associated With HIV-TB Co-Infection Treatment
Authors: Pooranagangadevi Navaneethapandian , Padmapriyadarsini Chandrasekaran
Published: May 2022

Tuberculosis (TB) is a communicable disease that is a major source of illness, one of the ten causes of mortality worldwide, and the largest cause of death from a single infectious agent Mycobacterium tuberculosis. HIV infection and TB are a fatal combination, with each speeding up the progression of the other. Barriers to integrated treatment as well as safety concerns on the co-management of HIV- TB co-infection do exist. Many HIV TB co-infected people require concomitant anti-retroviral therapy (ART) and anti-TB medication, which increases survival but also introduces certain management issues, such as drug interactions, combined drug toxicities, and TB immune reconstitution inflammatory syndrome which has been reviewed here. In spite of considerable pharmacokinetic interactions between antiretrovirals and antitubercular drugs, when the pharmacological characteristics of drugs are known and appropriate combination regimens, dosing, and timing of initiation are used, adequate clinical response of both infections can be achieved with an acceptable safety profile. To avoid undesirable drug interactions and side effects in patients, anti TB treatment and ART must be closely monitored. To reduce TB-related mortality among HIV-TB co-infected patients, ART and ATT (Anti Tuberculosis Treatment) outcomes must improve. Clinical practise should prioritise strategies to promote adherence, such as reducing treatment duration, monitoring and treating adverse events, and improving treatment success rates, to reduce the mortality risk of HIV-TB co-infection.
The Presence of a Substrate Strengthens The Jet Generated by Upside-Down Jellyfish
Authors: Battista Nicholas , Gaddam Manikantam G. , Hamlet Christina L. , Hoover Alexander P. , Miller Laura A. , Santhanakrishnan Arvind
Published: May 2022

Upside-down jellyfish, Cassiopea, are prevalent in warm and shallow parts of the oceans throughout the world. They are unique among jellyfish in that they rest upside down against the substrate and extend their oral arms upwards. This configuration allows them to continually pull water along the substrate, through their oral arms, and up into the water column for feeding, nutrient and gas exchange, and waste removal. Although the hydrodynamics of the pulsation of jellyfish bells has been studied in many contexts, it is not clear how the presence or absence of the substrate alters the bulk flow patterns generated by Cassiopea medusae. In this paper, we use three-dimensional (3D) particle tracking velocimetry and 3D immersed boundary simulations to characterize the flow generated by upside-down jellyfish. In both cases, the oral arms are removed, which allows us to isolate the effect of the substrate. The experimental results are used to validate numerical simulations, and the numerical simulations show that the presence of the substrate enhances the generation of vortices, which in turn augments the upward velocities of the resulting jets. Furthermore, the presence of the substrate creates a flow pattern where the water volume within the bell is ejected with each pulse cycle. These results suggest that the positioning of the upside-down jellyfish such that its bell is pressed against the ocean floor is beneficial for augmenting vertical flow and increasing the volume of water sampled during each pulse.
A Toolbox for Constructing a Stable Genetic Transformation Platform Allowing Foreign Fragment Integration in the Genome of Neopyropia yezoensis
Authors: Cao Xuexue , Kong Fanna , Sun Bin , Yin Jiqiang , Ren Hongzhong , Yue Huijie , Yu Chenggong , Tang Xianghai , Du Guoying , Wang Dongmei , Mao Yunxiang
Published: May 2022

Neopyropia yezoensis, previously known as Pyropia yezoensis, is regarded as a model macroalgae because of its economic value and typical intertidal seaweed species. However, the genetic transformation system to introduce foreign genes into its cells is inefficient and not stable. This study developed a more efficient transformation toolbox that allows the stable expression of foreign genes in N. yezoensis cells. We constructed an efficient transformation platform with the parameters of biolistic bombardment of 6 cm target distance, 600 μg gold particles/shot, 10 μg plasmid DNA/shot, 1,350 psi of helium, and 30 mmHg vacuum pressure. Thalli at 35 days of age were the most suitable transformation conditions, in which the highest transformation efficiency was generated. The endogenous promoter pPyACT1 could control gene expression efficiently compared to pPyUBC, pPyDPE2, and pPyEF1-a, especially the exogenous promoter d35S. Finally, the foreign genes PyGUS and PyHygR were stably expressed in different generations of transformants, including monospores, gametophytes, and filamentous sporophytes. Southern blotting analysis confirmed that PyGUS was integrated into the genome of N. yezoensis transformants. Establishing an efficient gene expression toolbox provides a strong foundation for functional genomics research and molecular genetic breeding on N. yezoensis.
Enhanced Cross-Shelf Exchange Between the Pacific Ocean and the Bungo Channel, Japan Related to a Heavy Rain Event
Authors: Morimoto Akihiko , Dong Menghong , Kameda Mahiro , Shibakawa Taiga , Hirai Makiko , Takejiri Kouhei , Guo Xinyu , Takeoka Hidetaka
Published: May 2022

A heavy rain event occurred in early July 2018 near the Seto Inland Sea. Despite clear weather after the heavy rain, the water temperature at 5 m depth on the eastern coast of the Bungo Channel decreased by approximately 3°C. Postulating that the water temperature decrease was related to the heavy rain event, we analyzed observed data during and after the heavy rain and conducted numerical experiments. We found that the surface water temperature decrease was caused by vertical mixing of cold water supplied from the Pacific Ocean in the bottom layer. Numerical experiments revealed that the bottom cold water from the Pacific Ocean was not controlled by the heavy rain event but was intensified by the heavy rain event. The lower salinity (lower water density) due to the heavy rain lasted until the end of August. This lower density intensified the gravitational circulation in the Bungo Channel for 2 months, which led to a 17.5% increase in inflow from the Pacific Ocean in the bottom layer and a 20% increase in the dissolved inorganic nitrogen flux to the Bungo Channel.
Towards Quantitative Inference of Nanoscale Defects in Irradiated Metals and Alloys
Authors: Hirst Charles A. , Dennett Cody A.
Published: May 2022

Quantifying the population of nanoscale defects that are formed in metals and alloys exposed to extreme radiation environments remains a pressing challenge in materials science. These defects both fundamentally alter material properties and seed long-timescale performance degradation, which often limits the lifespan of engineering systems. Unlike ceramic and semiconducting materials, these defects in metals and alloys are not spectroscopically active, forcing characterization to rely on indirect measurements from which the distribution of nanoscale defects may be inferred. In this mini-review, different experimental methodologies which have been employed for defect inference are highlighted to capture the current state of the art. Future directions in this area are proposed, which, by combining data streams from multiple and complementary characterization methods in concert with multi-scale modeling and simulation, will enable the ultimate goal of quantifying the full spectrum of defects in irradiated metals and alloys.
AgNP-AC Composite Fibers and its Adsorption and Antibacterial Properties
Authors: Liu Dandan , Zhang Chuanwei , Wang Bin , Quan Wenwen , Xu Chao
Published: May 2022

In this study, the electrospinning method was used to prepare silver nanoparticle–activated carbon (AgNP-AC) composite nanofiber membranes, aiming to obtain a high-performance dual-functional filter composite fiber membrane with good antibacterial and adsorption properties. A scanning electron microscope (SEM), X-ray diffractometer (XRD), and other instruments were used to characterize the morphology and structure of the composite nanofibers. The effects of different concentrations of activated carbon, silver, and polymer (polyethylene–vinyl alcohol—EVOH) on the fiber morphology were discussed. The adsorption performance and antibacterial performance of the composite fiber membrane were investigated to verify the mutual influence of silver and activated carbon. The results show that with the increase in the activated carbon and silver concentration, the fiber diameter of the AgNP-AC membrane increase and the diameter distribution tends to become uniform. When the mass fraction of polymer EVOH is 10% and the concentration ratio of silver nitrate and carbon is 0.05 and 0.085 (g/ml), the adsorption performance of the composite fiber membrane is at the best with an adsorption rate of 94.07%. The AgNP-AC composite nanofiber membrane also demonstrates a good antibacterial function against Staphylococcus aureus and is most effective in the first 8 h. However, it is found that the silver concentration is proportional to the antibacterial ability, but the activated carbon has a certain inhibitory effect on the antibacterial properties.
Clinical Relevance of the LVEDD and LVESD Trajectories in HF Patients With LVEF < 35%
Authors: Chen Yu-Chen , Hsing Shi-Chue , Chao Yuan-Ping , Cheng Yung-Wen , Lin Chin-Sheng , Lin Chin , Fang Wen-Hui
Published: May 2022

Background

Certain variables reportedly are associated with a change in left ventricular ejection fraction (LVEF) in heart failure (HF) with reduced ejection fraction (HFrEF). However, literature describing the association between the recovery potential of LVEF and parameters of ventricular remodeling in echocardiography remains sparse.

Methods

We recruited 2,148 HF patients with LVEF < 35%. All patients underwent at least two echocardiographic images. The study aimed to compare LVEF alterations and their association with patient characteristics and echocardiographic findings.

Results

Patients with “recovery” of LVEF (follow-up LVEF ≥ 50%) were less likely to have prior myocardial infarction (MI), had a higher prevalence of atrial fibrillation (Af), were less likely to have diabetes and hypertension, and had a smaller left atrium (LA) diameter, left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD), both in crude and in adjusted models (adjustment for age and sex). LVEDD cutoff values of 59.5 mm in men and 52.5 mm in women and LVESD cutoff values of 48.5 mm in men and 46.5 mm in women showed a year-to-year increase in the rate of recovery (follow-up LVEF ≥ 50%)/improvement (follow-up LVEF ≥ 35%), p-value < 0.05 in Kaplan–Meier estimates of the cumulative hazard curves.

Conclusions

Our study shows that LVEDD and LVESD increments in echocardiography can be predictors of changes in LVEF in in HF patients with LVEF < 35%. They may be used to identify patients who require more aggressive therapeutic interventions.
Salivary Alpha Amylase Bronchial Measure for Early Aspiration Pneumonia Diagnosis in Patients Treated With Therapeutic Hypothermia After Out-of-hospital Cardiac Arrest
Authors: Moussali Anis , Cauchois Emi , Carvelli Julien , Hraeich Sami , Bouzana Fouad , Lesaux Audrey , Boucekine Mohamed , Bichon Amandine , Gainnier Marc , Fromonot Julien , Bourenne Jeremy
Published: May 2022

Background

Aspiration pneumonia is the most common respiratory complication following out-of-hospital cardiac arrests (OHCA). Alpha-amylase (α-amylase) in pulmonary secretions is a biomarker of interest in detecting inhalation. The main goal of this study is to evaluate the performance of bronchoalveolar levels of α-amylase in early diagnosis of aspiration pneumonia, in patients admitted to intensive care unit (ICU) after OHCA.

Methods

This is a prospective single-center trial, led during 5 years (July 2015 to September 2020). We included patients admitted to ICU after OHCA. A protected specimen bronchial brushing and a mini-bronchoalveolar lavage (mini-BAL) were collected during the first 6 h after admission. Dosage of bronchial α-amylase and standard bacterial analysis were performed. Investigators confirmed pneumonia diagnosis using clinical, radiological, and microbiological criteria. Every patient underwent targeted temperature management.

Results

88 patients were included. The 34% (30 patients) developed aspiration pneumonia within 5 days following admission. The 55% (17) of pneumonias occurred during the first 48 h. The 57% of the patients received a prophylactic antibiotic treatment on their admission day. ICU mortality was 50%. Median value of bronchial α-amylase did not differ whether patients had aspiration pneumonia (15 [0–94]) or not (3 [0–61], p = 0,157). Values were significantly different concerning early-onset pneumonia (within 48 h) [19 (7–297) vs. 3 (0–82), p = 0,047]. If one or more microorganisms were detected in the initial mini-BAL, median value of α-amylase was significantly higher [25 (2–230)] than in sterile cultures (2 [0–43], p = 0,007). With an 8.5 IU/L cut-point, sensitivity and specificity of α-amylase value for predicting aspiration pneumonia during the first 2 days were respectively 74 and 62%. True positive and negative rates were respectively 44 and 86%. The area under the ROC curve was 0,654 (CI 95%; 0,524–0,785). Mechanical ventilation duration, length of ICU stay, and mortality were similar in both groups.

Conclusion

In our study, dosage of bronchial α-amylase was not useful in predicting aspiration pneumonia within the first 5 days after ICU admission for OHCA. Performance in predicting early-onset pneumonia was moderate.
Therapeutic Effects of Cold Atmospheric Plasma on Solid Tumor
Authors: Min Tianhao , Xie Xin , Ren Kaijie , Sun Tuanhe , Wang Haonan , Dang Chengxue , Zhang Hao
Published: May 2022

Cancer is a devastating disease, and there is no particularly effective treatment at present. Recently, a new treatment, cold atmospheric plasma (CAP), has been proposed. At present, CAP is confirmed to have selective killing effect on tumor by many studies in vitro and in vivo. A targeted literature search was carried out on the study of cold atmospheric plasma. Through analysis and screening, a narrative review approach was selected to describe therapeutic effects of cold atmospheric plasma on solid tumor. According to the recent studies on plasma, some hypothetical therapeutic schemes of CAP are proposed in this paper. The killing mechanism of CAP on solid tumor is expounded in terms of the selectivity of CAP to tumor, the effects of CAP on cells, tumor microenvironment (TME) and immune system. CAP has many effects on solid tumors, and these effects are dose-dependent. The effects of optimal doses of CAP on solid tumors include killing tumor cells, inhibiting non-malignant cells and ECM in TME, affecting the communication between tumor cells, and inducing immunogenic death of tumor cells. In addition, several promising research directions of CAP are proposed in this review, which provide guidance for future research.
A Novelly Developed Bipolar Needle Knife Can Be an Alternative Device Choice for Endoscopic Submucosal Dissection (With Video)
Authors: Chen Shengsen , Zhou Danping , Yu Jiangping , Ruan Rongwei , Liu Yuanshun , Li Yandong , Shen Qiwen , Wang Shi
Published: May 2022

Background

Endoscopic submucosal dissection (ESD) is technically difficult with high rates of complications, such as perforation and bleeding. We aimed to explore the safety and cutting efficiency of a novelly devised bipolar knife for ESD procedure.

Methods

Taking a traditional monopolar knife as a reference, the safety and feasibility of the novel bipolar knife were evaluated by an animal experiment and a human study. Furthermore, we assessed the usefulness and advantage of this novel bipolar knife by using the finite element method.

Results

A porcine experiment confirmed that there was no significant difference in wound size and cutting speed between the monopolar and bipolar knives. The thermal damage and histopathological scores produced by the two knives were similar. In addition, the porcine experiment and patients' study identified that the incidence of postoperative complications, such as bleeding, perforation, and infection, had no statistical difference between the monopolar and bipolar groups. Finally, the finite element model showed that the length and depth of thermal damage caused by the bipolar knife were, respectively, 102.77–117.98% and 80.87–84.53% of those caused by the monopolar knife at the same power.

Conclusion

The novel bipolar knife was theoretically safer than the monopolar knife and, at least, was confirmed not inferior to the monopolar knife in operability and cutting efficiency. Thus, the novel bipolar knife can be an alternative device choice for ESD.
An Enhanced Positional Error Compensation Method for Rock Drilling Robots Based on LightGBM and RBFN
Authors: Zhou Xuanyi , Bai Wenyu , He Jilin , Dai Ju , Liu Peng , Zhao Yuming , Bao Guanjun
Published: May 2022

Rock drilling robots are able to greatly reduce labor intensity and improve efficiency and quality in tunnel construction. However, due to the characteristics of the heavy load, large span, and multi-joints of the robot manipulator, the errors are diverse and non-linear, which pose challenges to the intelligent and high-precision control of the robot manipulator. In order to enhance the control accuracy, a hybrid positional error compensation method based on Radial Basis Function Network (RBFN) and Light Gradient Boosting Decision Tree (LightGBM) is proposed for the rock drilling robot. Firstly, the kinematics model of the robotic manipulator is established by applying MDH. Then a parallel difference algorithm is designed to modify the kinematics parameters to compensate for the geometric error. Afterward, non-geometric errors are analyzed and compensated by applying RBFN and lightGBM including features and kinematics model. Finally, the experiments of the error compensation by combing combining the geometric and non-geometric errors verify the performance of the proposed method.
Impact of Stress Hyperglycemia on Early Neurological Deterioration in Acute Ischemic Stroke Patients Treated With Intravenous Thrombolysis
Authors: Wang Ling , Cheng Qiantao , Hu Ting , Wang Nuo , Wei Xiu'e , Wu Tao , Bi Xiaoying
Published: May 2022

Background and Purpose

It has been widely reported that stress hyperglycemia contributes to poor prognosis in patients experiencing acute ischemic stroke (AIS). However, its predictive value for early neurological deterioration (END) after intravenous administration of recombinant tissue-type plasminogen activator (IV-rtPA) in AIS patients is still unclear. The aim of this study was to evaluate the impact of stress hyperglycemia on the risk of END after IV-rtPA.

Methods

A total of 798 consecutive patients treated with IV-rtPA were included in this study. The stress hyperglycemia ratio (SHR) was calculated as fasting plasma glucose level at admission (mg/dl)/glycosylated hemoglobin (HbAlc) (%). END was defined as a National Institutes of Health Stroke Scale Score (NIHSS) ≥ 4 points 24 h after IV-rtPA, and poor functional outcome at discharge was defined as a modified Rankin Scale (mRS) score of 3–6 at discharge. Patients with a prior history of diabetes or HbAlc ≥ 6.5% were considered to have diabetes mellitus. Patients were grouped according to SHR values. Multivariate logistical regression was used to evaluate the risk of END for patients within specific SHR categories.

Results

In total, 139 (17.4%) patients had END. After adjusting for confounders, the highest tertile group had higher risks of END and poor functional outcome at discharge than those of patients in the lowest tertile group (OR, 1.95; 95% CI, 1.21–3.15; p = 0.006) (OR, 1.85; 95% CI, 1.163–2.941; p = 0.009), and the predictive value of high SHR for END was also significant in patients with diabetes mellitus (OR, 3.05; 95% CI, 1.29–7.21; p = 0.011). However, a significant association of high SHR and poor functional outcome was only found in patients without diabetes (OR, 1.85; 95% CI, 1.002–3.399; p = 0.045).

Conclusion

A higher SHR predicted that patients with severe stress hyperglycemia had higher risks of END and poor functional outcome at discharge after IV-rtPA.
Sleep Disturbances in Pediatric Craniopharyngioma: A Systematic Review
Authors: Cordani Ramona , Veneruso Marco , Napoli Flavia , Di Iorgi Natascia , Milanaccio Claudia , Consales Alessandro , Disma Nicola , De Grandis Elisa , Maghnie Mohamad , Nobili Lino
Published: May 2022

Craniopharyngiomas are rare brain tumors of the sellar region and are the most common non-neuroepithelial intracerebral neoplasm in children. Despite a low-grade histologic classification, craniopharyngiomas can have a severe clinical course due to hypothalamic involvement. The hypothalamus plays a crucial role in regulating vital functions, and it is a critical component of the sleep-wake regulatory system. This systematic review aims to provide an overview of the current knowledge on sleep disorders in patients with craniopharyngioma to unravel their underlying mechanisms and identify possible therapeutic strategies. A comprehensive electronic literature search of the PubMed/MEDLINE and Scopus databases was conducted in accordance with the PRISMA® statement. Extensively published, peer-reviewed articles involving patients with childhood craniopharyngioma and focused on this specific topic were considered eligible for inclusion. Thirty-two articles were included; a high prevalence of excessive daytime sleepiness was reported in CP patients, with wide variability (25–100%) depending on the diagnostic method of detection (25–43% by subjective measures, 50–100% by objective investigations). In particular, secondary narcolepsy was reported in 14–35%, sleep-disordered breathing in 4–46%. Moreover, sleep-wake rhythm dysregulation has been notified, although no prevalence data are available. Possible mechanisms underlying these disorders are discussed, including hypothalamic injury, damage to the suprachiasmatic nucleus, low melatonin levels, hypocretin deficiency, and hypothalamic obesity. The diagnosis and management of sleep disorders and associated comorbidities are challenging. This review summarizes the pathophysiology of sleep disorders in childhood-onset CP and the main treatment options. Finally, a possible diagnostic algorithm in order to accurately identify and treat sleep disorders in these patients is proposed.
Microscopy-BIDS: An Extension to the Brain Imaging Data Structure for Microscopy Data
Authors: Bourget Marie-Hélène , Kamentsky Lee , Ghosh Satrajit S. , Mazzamuto Giacomo , Lazari Alberto , Markiewicz Christopher J. , Oostenveld Robert , Niso Guiomar , Halchenko Yaroslav O. , Lipp Ilona , Takerkart Sylvain , Toussaint Paule-Joanne , Khan Ali R. , Nilsonne Gustav , Castelli Filippo Maria ,   The BIDS Maintainers, Cohen-Adad Julien
Published: May 2022

The Brain Imaging Data Structure (BIDS) is a specification for organizing, sharing, and archiving neuroimaging data and metadata in a reusable way. First developed for magnetic resonance imaging (MRI) datasets, the community-led specification evolved rapidly to include other modalities such as magnetoencephalography, positron emission tomography, and quantitative MRI (qMRI). In this work, we present an extension to BIDS for microscopy imaging data, along with example datasets. Microscopy-BIDS supports common imaging methods, including 2D/3D, ex/in vivo, micro-CT, and optical and electron microscopy. Microscopy-BIDS also includes comprehensible metadata definitions for hardware, image acquisition, and sample properties. This extension will facilitate future harmonization efforts in the context of multi-modal, multi-scale imaging such as the characterization of tissue microstructure with qMRI.
Treatment With Nimodipine or FK506 After Facial Nerve Repair Neither Improves Accuracy of Reinnervation Nor Recovery of Mimetic Function in Rats
Authors: Barham Mohammed , Streppel Michael , Guntinas-Lichius Orlando , Fulgham-Scott Nicole , Vogt Johannes , Neiss Wolfram F.
Published: May 2022

Purpose

Nimodipine and FK506 (Tacrolimus) are drugs that have been reported to accelerate peripheral nerve regeneration. We therefore tested these substances aiming to improve the final functional outcome of motoric reinnervation after facial nerve injury.

Methods

In 18 female rats, the transected facial nerve was repaired by an artificial nerve conduit. The rats were then treated with either placebo, nimodipine, or FK506, for 56 days. Facial motoneurons were pre-operatively double-labeled by Fluoro-Gold and again 56 days post-operation by Fast-Blue to measure the cytological accuracy of reinnervation. The whisking motion of the vibrissae was analyzed to assess the quality of functional recovery.

Results

On the non-operated side, 93–97% of those facial nerve motoneurons innervating the vibrissae were double-labeled. On the operated side, double-labeling only amounted to 38% (placebo), 40% (nimodipine), and 39% (FK506), indicating severe misdirection of reinnervation. Regardless of post-operative drug or placebo therapy, the whisking frequency reached 83–100% of the normal value (6.0 Hz), but whisking amplitude was reduced to 33–48% while whisking velocity reached 39–66% of the normal values. Compared to placebo, statistically neither nimodipine nor FK506 improved accuracy of reinnervation and function recovery.

Conclusion

Despite previous, positive data on the speed and quantity of axonal regeneration, nimodipine and FK506 do not improve the final functional outcome of motoric reinnervation in rats.
Bladder Oxidative Stress and HMGB1 Release Contribute to PAR4-Mediated Bladder Pain in Mice
Authors: Ye Shaojing , Ma Fei , Mahmood Dlovan F. D. , Meyer-Siegler Katherine L. , Leng Lin , Bucala Richard , Vera Pedro L.
Published: May 2022

Activation of intravesical PAR4 receptors leads to bladder hyperalgesia (BHA) through release of urothelial macrophage migration inhibitory factor (MIF) and urothelial high mobility group box-1 (HMGB1). MIF deficiency and/or MIF antagonism at the bladder block BHA in mice yet the mechanisms are not clear. Since oxidative stress and ERK phosphorylation are involved in MIF signaling we hypothesized that oxidative stress and/or ERK signaling, activated by MIF release, promote intravesical HMGB1 release to induce BHA. We induced BHA by intravesical PAR4 infusion in female C57BL/6 mice. Mechanical sensitivity was evaluated by measuring abdominal von Frey (VF) 50% thresholds before (baseline) and 24 h post-infusion. Intravesical pre-treatment (10 min infusion prior to PAR4) with N-acetylcysteine amide (NACA; reactive-oxygen species scavenger; 3 mg in 50 μl), FR180204 (selective ERK1/2 inhibitor; 200 μg in 50 μl), ethyl pyruvate (EP; HMGB1 release inhibitor; 600 μg in 50 μl), or diluent controls (50 μl) tested the effects of pre-treatment on PAR4-induced BHA. Intravesical fluid was collected after each treatment and HMGB1 concentration was measured using ELISA. Awake micturition parameters (volume and frequency) were assessed at the end of the experiments. Bladders were collected and examined for histological signs of edema and inflammation. Pre-treatment with PBS followed by PAR4 induced BHA in mice but PBS followed by scrambled peptide did not. Pre-treatment with NACA or EP partially blocked PAR4-induced BHA while FR180204 had no effect. A significant correlation between intravesical HMGB1 levels and 50% VF thresholds was observed. All PAR4 treated groups had increased levels of HMGB1 in the intravesical fluid compared to PBS-Scrambled group although not statistically significant. No significant effects were noted on awake micturition volume, micturition frequency or histological evidence of bladder edema or inflammation. Our results show that intravesical antagonism of bladder reactive-oxygen species accumulation was effective in reducing PAR4-induced bladder pain. The correlation between intravesical levels of HMGB1 and bladder pain indicates that released HMGB1 is pivotal to bladder pain. Thus, modulating events in the MIF signaling cascade triggered by PAR4 activation (including bladder oxidative stress and HMGB1 release) warrant further investigation as possible therapeutic strategies.
DWI Combined With Hepatobiliary-Phase Enhanced Imaging Can Better Differentiate Cholangiocarcinoma From Atypical Liver Abscesses
Authors: Xing Li-Hong , Zhuo Li-Yong , Zhang Yu , Ma Xi , Ma Ze-Peng , Zhao Ying-Jia , Yin Xiao-Ping , Gao Bu-Lang
Published: May 2022

Objective

To investigate the value of diffusion-weighted imaging (DWI) combined with the hepatobiliary phase (HBP) Gd-BOPTA enhancement in differentiating intrahepatic mass-forming cholangiocarcinoma (IMCC) from atypical liver abscess.

Materials and Methods

A retrospective analysis was performed on 43 patients with IMCCs (IMCC group) and 25 patients with atypical liver abscesses (liver abscess group). The DWI signal, the absolute value of the contrast noise ratio (│CNR│) at the HBP, and visibility were analyzed.

Results

A relatively high DWI signal and a relatively high peripheral signal were presented in 29 patients (67.5%) in the IMCC group, and a relatively high DWI signal was displayed in 15 patients (60.0%) in the atypical abscess group with a relatively high peripheral signal in only one (6.7%) patient and a relatively high central signal in 14 (93.3%, 14/15). A significant (P<0.001) difference existed in the pattern of signal between the two groups of patients. On T2WI, IMCC was mainly manifested by homogeneous signal (53.5%), whereas atypical liver abscesses were mainly manifested by heterogeneous signal and relatively high central signal (32%, and 64%), with a significant difference (P<0.001) in T2WI imaging presentation between the two groups. On the HBP imaging, there was a statistically significant difference in peripheral │CNR│ (P< 0.001) and visibility between two groups. The sensitivity of the HBP imaging was significantly (P=0.002) higher than that of DWI. The sensitivity and accuracy of DWI combined with enhanced HBP imaging were significantly (P=0.002 and P<0.001) higher than those of either HBP imaging or DWI alone.

Conclusion

Intrahepatic mass-forming cholangiocarcinoma and atypical liver abscesses exhibit different imaging signals, and combination of DWI and hepatobiliary-phase enhanced imaging has higher sensitivity and accuracy than either technique in differentiating intrahepatic mass-forming cholangiocarcinoma from atypical liver abscesses.
Non-Coding RNA in Penile Cancer
Authors: Pinho Jaqueline Diniz , Silva Gyl Eanes Barros , Teixeira-Júnior Antonio Augusto Lima , Rocha Thalita Moura Silva , Batista Lecildo Lira , de Sousa Amanda Marques , Calixto José de Ribamar Rodrigues , Burbano Rommel Rodrigues , Souza Carolina Rosal Teixeira de , Khayat André Salim
Published: May 2022

Penile cancer (PC) still presents a health threat for developing countries, in particular Brazil. Despite this, little progress has been made on the study of markers, including molecular ones, that can aid in the correct management of the patient, especially concerning lymphadenectomy. As in other neoplasms, non-coding RNAs (ncRNAs) have been investigated for penile cancer, with emphasis on microRNAs, piRNAs (PIWI-interacting small RNAs), and long non-coding RNAs (LncRNAs). In this context, this review aims to assemble the available knowledge on non-coding RNA linked in PC, contributing to our understanding of the penile carcinogenesis process and addressing their clinical relevance. ncRNAs are part of the novel generation of biomarkers, with high potential for diagnosis and prognosis, orientating the type of treatment. Furthermore, its versatility regarding the use of paraffin samples makes it possible to carry out retrospective studies.
Clinical Strategies to Develop Connections, Promote Health and Address Pain From the Perspectives of Indigenous Youth, Elders, and Clinicians
Authors: VanEvery Rachel , Latimer Margot , Naveau Angela
Published: May 2022

In this article we discuss findings from a community based, participatory action research study. The aim was to understand how Indigenous youth describe, experience, manage pain and hurt and how they seek care. A critical analysis guided by Two-Eyed Seeing and Medicine Wheel frameworks highlighted important clinical strategies for Indigenous youth to balance their health and reduce pain. This study is a partnership project with an Aboriginal Health Centre in Southern Ontario and the Canadian Institute of Health Research funded Aboriginal Children's Hurt and Healing Initiative (ACHH). The study gathered perspectives of Indigenous youth, Elders, and health clinicians using conversation sessions guided by a First Nations doctoral student and nurse researcher. Using the medicine wheel framework three main thematic areas emerged across the three groups and include (1) Predictors of Imbalance; (2) Indicators of Imbalance; and (3) Strategies to re-establish balance health in relation to pain. The main strategy includes considerations for clinicians using the acronym LISTEN (Language, Individual, Share, Teachable moments, Engage, and Navigate) approach that outlines strategies for clinicians that will be a safe guide to manage pain and hurt.
Novel Mutations in ACP5 and SAMHD1 in a Patient With Pediatric Systemic Lupus Erythematosus
Authors: Hong Soon-Min , Chen Wei , Feng Jiaqi , Dai Dai , Shen Nan
Published: May 2022

Background

The study of genetic predisposition to pediatric systemic lupus erythematosus (pSLE) has brought new insights into the pathophysiology of SLE, as it is hypothesized that genetic predisposition is greater in children. Furthermore, identifying genetic variants and linking disrupted genes to abnormal immune pathways and clinical manifestations can be beneficial for both diagnosis and treatment. Here, we identified genetic alterations in a patient with childhood-onset SLE and analyzed the immunological mechanisms behind them to support future diagnosis, prognosis, and treatment.

Methods

Whole exome sequencing (WES) was adopted for genetic analysis of a patient with childhood-onset SLE. Gene mutations were confirmed by Sanger sequencing. Clinical data of this patient were collected and summarized. Ingenuity Pathway Analysis was used to provide interacting genes of the perturbed genes. Online Enrichr tool and Cytoscape software were used to analysis the related pathways of these genes.

Results

We present a case of a 2-year-old girl who was diagnosed with idiopathic thrombocytopenic purpura (ITP) and SLE. The patient was characterized by cutaneous bleeding spots on both lower extremities, thrombocytopenia, decreased serum complements levels, increased urinary red blood cells, and positive ANA and dsDNA. The patient was treated with methylprednisolone and mycophenolate, but clinical remission could not be achieved. The genomic analysis identified three novel mutations in this pSLE patient, a double-stranded missense mutation in ACP5 (c.1152G>T and c.420G>A) and a single-stranded mutation in SAMHD1 (c.1423G>A). Bioinformatic analysis showed that these two genes and their interacting genes are enriched in the regulation of multiple immune pathways associated with SLE, including cytokine signaling and immune cell activation or function. Analysis of the synergistic regulation of these two genes suggests that abnormalities in the type I interferon pathway caused by genetic variants may contribute to the pathogenesis of SLE.

Conclusion

The combined complexity of polymorphisms in the coding regions of ACP5 and SAMHD1 influences the susceptibility to SLE. Alterations in these genes may lead to abnormalities in the type I interferon pathway. Our study extends the spectrum of mutations in the ACP5 and SAMHD1 genes. The identification of these mutations could aid in the diagnosis of SLE with genetic counseling and suggest potential precise treatments for specific pathways.
Cannabinoid CB2 Receptors Modulate Microglia Function and Amyloid Dynamics in a Mouse Model of Alzheimer’s Disease
Authors: Ruiz de Martín Esteban Samuel , Benito-Cuesta Irene , Terradillos Itziar , Martínez-Relimpio Ana M. , Arnanz M. Andrea , Ruiz-Pérez Gonzalo , Korn Claudia , Raposo Catarina , Sarott Roman C. , Westphal Matthias V. , Elezgarai Izaskun , Carreira Erick M. , Hillard Cecilia J. , Grether Uwe , Grandes Pedro , Grande M. Teresa , Romero Julián
Published: May 2022

The distribution and roles of the cannabinoid CB2 receptor in the CNS are still a matter of debate. Recent data suggest that, in addition to its presence in microglial cells, the CB2 receptor may be also expressed at low levels, yet biologically relevant, in other cell types such as neurons. It is accepted that the expression of CB2 receptors in the CNS is low under physiological conditions and is significantly elevated in chronic neuroinflammatory states associated with neurodegenerative diseases such as Alzheimer’s disease. By using a novel mouse model (CB2EGFP/f/f), we studied the distribution of cannabinoid CB2 receptors in the 5xFAD mouse model of Alzheimer’s disease (by generating 5xFAD/CB2EGFP/f/f mice) and explored the roles of CB2 receptors in microglial function. We used a novel selective and brain penetrant CB2 receptor agonist (RO6866945) as well as mice lacking the CB2 receptor (5xFAD/CB2−/−) for these studies. We found that CB2 receptors are expressed in dystrophic neurite-associated microglia and that their modulation modifies the number and activity of microglial cells as well as the metabolism of the insoluble form of the amyloid peptide. These results support microglial CB2 receptors as potential targets for the development of amyloid-modulating therapies.
The Efficacy and Safety of Brolucizumab for the Treatment of nAMD: A Systematic Review and Meta-Analysis
Authors: Chuan Junlan , Liu Lianqiao , Feng Yumei , Wang Mengdan , Li Gang , Lv Qin
Published: May 2022

Introduction: As demonstrated in pivotal clinical trials, brolucizumab can be used to treat neovascular age-related macular degeneration (nAMD) because it antagonizes vascular endothelial growth factor (VEGF) in the vitreous. However, brolucizumab may cause retinal vasculitis obliterans in the presence of inflammation in the eyes. In the present study, a meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the efficacy and safety of brolucizumab.

Methods:ClinicTrail.gov., Embase, Cochrane Library, and PubMed were retrieved from inception until 31 December 2021 for RCTs assessing the efficacy and safety of brolucizumab. Changes in best corrected visual acuity (BCVA) and central sub-field thickness (CSFT) and incidence of adverse events, serious adverse events, and serious ocular adverse events were extracted from eligible RCTs. A meta-analysis was performed using RevMan 5.4.1.

Results: A total of six RCTs with 3,574 participants were finally involved in this meta-analysis. The changes of best corrected visual acuity (BCVA) showed no statistically significant difference between the brolucizumab-treated group and aflibercept-treated group. Brolucizumab induced higher central sub-field thickness (CSFT) reduction than the control agent (aflibercept). The incidence of adverse events was similar between the brolucizumab group and control group (OR 0.63, 95% CI 0.37 to 1.08, p = 0.09), and brolucizumab caused fewer serious adverse events (OR 0.78, 95% CI 0.63 to 0.95, p = 0.01). However, brolucizumab could lead to more serious ocular adverse events than Lucentis and aflibercept (OR 2.15, 95% CI 1.11 to 4.16, p = 0.02).

Conclusion: Brolucizumab was non-inferior to other anti-VEGF agents in improving BCVA and decreasing CSFT. But it caused more serious ocular adverse events which is worthy of special attention by ophthalmologists.
The Therapeutic Benefits of Nanoencapsulation in Drug Delivery to the Anterior Segment of the Eye: A Systematic Review
Authors: Bhandari Madhavi , Nguyen Sanko , Yazdani Mazyar , Utheim Tor Paaske , Hagesaether Ellen
Published: May 2022

Background: Although numerous nanoparticle formulations have been developed for ocular administration, concerns are being raised about a possible mismatch between potential promises made by the field of nanoparticle research and demonstration of actual therapeutic benefit. Therefore, the primary focus of this present review was to critically assess to what extent nanoencapsulation of ocular drugs improved the therapeutic outcome when treating conditions in the anterior segment of the eye.

Methods: A systematic search was conducted using Medline, PubMed, and Embase databases as well as Google Scholar for published peer-reviewed articles in English focusing on conventional nanoparticles used as drug delivery systems to the anterior segment of the eye in in vivo studies. The major therapeutic outcomes were intraocular pressure, tear secretion, number of polymorphonuclear leucocytes and pupil size. The outcome after encapsulation was compared to the non-encapsulated drug.

Results: From the search, 250 results were retrieved. Thirty-eight studies met the inclusion criteria. Rabbits were used as study subjects in all but one study, and the number of animals ranged from 3 to 10. Coated and uncoated liposomes, lipid-based and polymeric nanoparticles, as well as micelles, were studied, varying in both particle size and surface charge, and encapsulating a total of 24 different drugs, including 6 salts. The majority of the in vivo studies demonstrated some improvement after nanoencapsulation, but the duration of the benefit varied from less than 1 h to more than 20 h. The most common in vitro methods performed in the studies were drug release, transcorneal permeation, and mucin interaction.

Discussion: Nanoparticles that are small and mucoadhesive, often due to positive surface charge, appeared beneficial. Although in vitro assays can unravel more of the hidden and sophisticated interplay between the encapsulated drug and the nanoparticle structure, they suffered from a lack of in vitro—in vivo correlation. Therefore, more research should be focused towards developing predictive in vitro models, allowing rational design and systematic optimization of ocular nanoparticles with minimal animal experimentation.