bluuebunny/crossref_metadata_2025 huggingface dataset:
Three‐dimensional reconstruction of interstitial extracellular vesicles in human liver as determined by electron tomography
Authors: Olofsson Bagge Roger , Berndtsson Jens , Urzì Ornella , Lötvall Jan , Micaroni Massimo , Crescitelli Rossella
Published: November 2023

Extracellular vesicles (EVs) are lipid bilayer nanoparticles involved in cell‐cell communication that are released into the extracellular space by all cell types. The cargo of EVs includes proteins, lipids, nucleic acids, and metabolites reflecting their cell of origin. EVs have recently been isolated directly from solid tissues, and this may provide insights into how EVs mediate communication between cells in vivo. Even though EVs have been isolated from tissues, their point of origin when they are in the interstitial space has been uncertain. In this study, we performed three‐dimensional (3D) reconstruction using transmission electron tomography of metastatic and normal liver tissues with a focus on the presence of EVs in the interstitium. After chemical fixation of the samples and subsequent embedding of tissue pieces in resin, ultrathin slices (300 nm) were cut and imaged on a 120 ekV transmission electron microscopy as a tilt series (a series of subsequent images tilted at different angles). These were then computationally illustrated in a 3D manner to reconstruct the imaged tissue volume. We identified the cells delimiting the interstitial space in both types of tissues, and small distinct spherical structures with a diameter of 30–200 nm were identified between the cells. These round structures appeared to be more abundant in metastatic tissue compared to normal tissue. We suggest that the observed spherical structures in the interstitium of the metastatic and non‐metastatic liver represent EVs. This work thus provides the first 3D visualization of EVs in human tissue.
Utility of panenteric capsule endoscopy for the detection of small‐bowel Crohn's disease in patients with a normal magnetic resonance enterography: A prospective observational pilot study
Authors: Bohra Anuj , Lewis Diana , Segal Jonathan P , Vasudevan Abhinav , Van Langenberg Daniel R , Niewiadomski Olga
Published: November 2023

Background and Aim

Capsule endoscopy allows the direct visualization of the small bowel. We examined the diagnostic utility of a new modality, namely panenteric Crohn's capsule endoscopy (CE), in detecting active small‐bowel Crohn's disease (CD) in those with normal magnetic resonance enterography (MRE).

Methods

We prospectively recruited patients with a diagnosis of CD or suspected small‐bowel CD in whom the MRE was normal. Inclusion criteria included abdominal symptoms and abnormal serum or fecal biomarkers. The primary outcome was the detection of active small‐bowel CD (measured through the Lewis score [LS]). Secondary outcomes included change in Montreal classification for those with a pre‐existing CD diagnosis, change in medical therapy, clinical activity, and biomarkers at baseline and 6 months, and quality‐of‐life measures.

Results

A total of 22 patients with a diagnosis of CD or suspected new diagnosis were recruited, with CE complete to the caecum in 21 and 18/21 (86%) showing evidence of active small‐bowel CD (LS > 135). Of the patients with a pre‐existing diagnosis of CD, 9/11 (82%) had a change in Montreal classification. At 6 months following CE, 17/18 (94%) had clinician‐directed change in therapy. This correlated with an improvement in the quality of life (P < 0.05 as per the Short Inflammatory Bowel Disease Questionnaire), a reduction in the Harvey Bradshaw index (median: 7–4, P < 0.001), and favorable CRP and albumin response.

Conclusion

Crohn's CE is a useful diagnostic test for assessing active small‐bowel CD when imaging is normal but clinical suspicion is high. Crohn's CE should be integrated into the diagnostic algorithm for small‐bowel CD.
NAAG synthetase deficiency has only low influence on pathogenesis in a Canavan disease mouse model
Authors: Becker Ivonne , Wang‐Eckhardt Lihua , Eckhardt Matthias
Published: November 2023

Canavan disease (CD) is a leukodystrophy caused by mutations in the N‐acetylaspartate (NAA) hydrolase aspartoacylase (ASPA). Inability to degrade NAA and its accumulation in the brain results in spongiform myelin degeneration. NAA is mainly synthesized by neurons, where it is also a precursor of the neuropeptide N‐acetylaspartylglutamate (NAAG). Hydrolysis of this peptide by glutamate carboxypeptidases is an additional source of extracellular NAA besides the instant neuronal release of NAA. This study examines to what extent NAA released from NAAG contributes to NAA accumulation and pathogenesis in the brain of Aspanur7/nur7 mutant mice, an established model of CD. Towards this aim, Aspanur7/nur7 mice with additional deficiencies in NAAG synthetase genes Rimklb and/or Rimkla were generated. Loss of myelin in Aspanur7/nur7 mice was not significantly affected by Rimkla and Rimklb deficiency and there was also no obvious change in the extent of brain vacuolation. Astrogliosis was slightly reduced in the forebrain of Rimkla and Rimklb double deficient Aspanur7/nur7 mice. However, only minor improvements at the behavioral level were found. The brain NAA accumulation in CD mice was, however, not significantly reduced in the absence of NAAG synthesis. In summary, there was only a weak tendency towards reduced pathogenic symptoms in Aspanur7/nur7 mice deficient in NAAG synthesis. Therefore, we conclude that NAAG metabolism has little influence on NAA accumulation in Aspanur7/nur7 mice and development of pathological symptoms in CD.
Characterization of orthopedic manifestations in patients with mucopolysaccharidosis II using data from 15 years of the Hunter Outcome Survey
Authors: Link Bianca , Botha Jaco , Giugliani Roberto
Published: November 2023

Mucopolysaccharidosis II (MPS II) is a rare, life‐limiting lysosomal storage disease caused by reduced iduronate‐2‐sulfatase activity. Patients experience broad ranging signs and symptoms, including bone and joint manifestations. This study reported on orthopedic involvement and management in patients with MPS II using 15 years of data from the Hunter Outcome Survey (HOS). Of the 245 patients in the study population, 90.2% had skeletal deformity (median onset, 2.8 years), 76.7% had upper body stiffness (onset, 4.2 years), and 61.2% had lower body stiffness (onset, 5.3 years); 63.7% of patients had at least three joint manifestations. Orthopedic manifestations were common in adults and children with MPS II, and in patients with and without cognitive impairment. Joint range of motion (JROM) was restricted in all joints assessed (shoulder, elbow, hip, wrist, knee, and ankle). Little correlation was observed between JROM measurements, subjective reports of joint stiffness and limited function, and 6‐minute walk test results. Patients with joint stiffness and limited function were generally more likely to have central and peripheral nervous system, pulmonary, and cardiovascular manifestations than those without these symptoms. Carpal tunnel decompression was the most common orthopedic surgery (recorded in 49/245 patients [20.0%]), but orthopedic surgeries were uncommon overall. Our findings highlight the need for routine monitoring of orthopedic manifestations using multiple assessment types in patients with MPS II to help inform clinical decision‐making and improve patient quality of life. They also underline the contribution of factors other than orthopedic manifestations to the walking ability of patients with MPS II.
Virological characteristics and the rapid antigen test as deisolation criteria in immunocompromised patients with COVID‐19: A prospective cohort study
Authors: Kang Sung‐Woon , Kim Jun‐Won , Kim Ji Yeun , Lim So Yun , Jang Choi‐Young , Chang Euijin , Yang Jeong‐Sun , Kim Kyung‐Chang , Jang Hee‐Chang , Kim Dasol , Shin Younmin , Lee Joo‐Yeon , Kim Sung‐Han
Published: November 2023

There are limited data supporting current Centers for Disease Control and Prevention guidelines for the isolation period in moderate to severely immunocompromised patients with coronavirus disease 2019 (COVID‐19). Adult COVID‐19 patients who underwent solid organ transplantation (SOT) or received active chemotherapy against hematologic malignancy were enrolled and weekly respiratory samples were collected. Samples with positive genomic real‐time polymerase chain reaction results underwent virus culture and rapid antigen testing (RAT). A total of 65 patients (40 with hematologic malignancy and 25 SOT) were enrolled. The median duration of viable virus shedding was 4 weeks (interquartile range: 3–7). Multivariable analysis revealed that B‐cell depletion (hazard ratio [HR]: 4.76) was associated with prolonged viral shedding, and COVID‐19 vaccination (≥3 doses) was negatively associated with prolonged viral shedding (HR: 0.22). The sensitivity, specificity, positive predictive value, and negative predictive value of RAT for viable virus shedding were 79%, 76%, 74%, and 81%, respectively. The negative predictive value of RAT was only 48% (95% confidence interval [CI]: 33–65) in the samples from those with symptom onset ≤20 days, but it was as high as 92% (95% CI: 85–96) in the samples from those with symptom onset >20 days. About half of immunocompromised COVID‐19 patients shed viable virus for ≥4 weeks from the diagnosis, and virus shedding was prolonged especially in unvaccinated patients with B‐cell‐depleting therapy treatment. RAT beyond 20 days in immunocompromised patients had a relatively high negative predictive value for viable virus shedding.
Resurgence of influenza during COVID‐19 in Chongqing, China: A retrospective analysis
Authors: Li Zhourong , Xiong Yu , Long Jiang , Li Tingting , Fu Xiaoqing , Yang Shuang , Tian Dechao , Zhao Yong , Qi Li
Published: November 2023

To better understand the trends of influenza and the impact of public health and social measures (PHSMs) implemented during the coronavirus disease 2019 (COVID‐19) period in Chongqing, China. Data from the China Influenza Surveillance Information System from January 2017 to June 2022 were extracted. Epidemiological characteristics (influenza‐like illness [ILI] and ILI%) and virological characteristics (influenza positive rate and circulating (sub)types) of influenza were described and compared between the pre‐COVID‐19 period and the COVID‐19 period. Our survey showed that the implementation of PHSMs during the COVID‐19 period had a positive impact on reducing influenza transmission. However, influenza activity resurged in 2021–2022 as the PHSMs were eased. Children under 5 years old constituted the highest proportion of ILI cases. The overall influenza positive rate was 23.70%, with a higher rate observed during the pre‐COVID‐19 period (31.55%) compared to the COVID‐19 period (13.68%). Influenza virus subtypes co‐circulated and the predominant subtype varied each year, with influenza A subtypes predominated in 2018/2019, while influenza B/Victoria lineage dominated in 2020/2021. PHSMs are effective measures to mitigate the spread of influenza. The findings underscore the need for bolstering monitoring systems, advocating influenza vaccination, and implementing practical PHSMs to strengthen prevention and control measures against influenza.
Macroscale neurovascular coupling and functional integration in end‐stage renal disease patients with cognitive impairment: A multimodal MRI study
Authors: Hu Runyue , Gao Lei , Chen Peina , Wei Xiaobao , Wu Xiaoyan , Xu Haibo
Published: November 2023

End‐stage renal disease (ESRD) is associated with vascular and neuronal dysfunction, causing neurovascular coupling (NVC) dysfunction, but how NVC dysfunction acts on the mechanism of cognitive impairment in ESRD patients from local to remote is still poorly understood. We recruited 48 ESRD patients and 35 demographically matched healthy controls to scan resting‐state functional MRI and arterial spin labeling, then investigated the four types of NVC between amplitude of low‐frequency fluctuation (ALFF), fractional ALFF, regional homogeneity, degree centrality, and cerebral blood perfusion (CBF), and associated functional networks. Our results indicated that ESRD patients showed NVC dysfunction in global gray matter and multiple brain regions due to the mismatch between CBF and neural activity, and associated disrupted functional connectivity (FC) within sensorimotor network (SMN), visual network (VN), default mode network (DMN), salience network (SN), and disrupted FC between them with limbic network (LN), while increased FC between SMN and DMN. Anemia may affect the NVC of middle occipital gyrus and precuneus, and increased pulse pressure may result in disrupted FC with SMN. The NVC dysfunction of the right precuneus, middle frontal gyrus, and parahippocampal gyrus and the FC between the right angular gyrus and the right anterior cingulate gyrus may reflect cognitive impairment in ESRD patients. Our study confirmed that ESRD patients may exist NVC dysfunction and disrupted functional integration in SMN, VN, DMN, SN and LN, serving as one of the mechanisms of cognitive impairment. Anemia and increased pulse pressure may be related risk factors.
Molecular identification of keratinophilic fungi associated with hair scalp and antifungal activity of green‐synthesis zinc oxide nanoparticles
Authors: El‐Dawy Eman Gamal Abd Elnaser M. , Gherbawy Youssuf A. , Abd El‐Sadek Mahmoud S. , Fouad Walaa
Published: November 2023

A diverse population of fungi colonizes human hair and skin due to millions of years of functional integration and mutual adaptation. The human body, with its fungal communities, forms a complex entity. Microbial imbalance is promoted by instabilities in the host–mycobiota interaction system, which can be related to the development of various diseases. By morphological and molecular identification, 15 genera comprising 24 species were isolated from 18 scalp samples collected from girls. Yeast‐like structures were the most common species in this study; they were recovered from six samples (33.3%). They were represented by five species: Arachniotus ruber; Cosmospora aurantiicola; Cutaneotrichosporon oleaginosum; Geotrichum candidum and Suhomyces tanzawaensis. For the synthesis of zinc oxide nanoparticles (ZnO NPs), an aqueous extract of Zingiber officinale was utilized as a reducing and capping agent. The prepared NPs tested by X‐ray diffraction, they had a hexagonal wurtzite structure. Most of the ZnO NPs were spherical, and their diameter was about 38.9 nm using a transmission electron microscope. ZnO NPs of the Fourier‐transform infrared spectroscopy spectra were recorded in the range of 400–4000 cm−1. UV–visible diffuse reflectance spectroscopy showed the 200–800 nm wavelength range. ZnO NPs showed the highest activity against Ambrosiella hartigii Ambh2; Cladosporium cladosporioides Cladcl12; C. cf. cucumerinum Cladcu13; S. tanzawaensis Suht34, with minimal inhibitory concentrations 1.25 × 103 µg/mL on the four isolates.
High‐performance bioelectronic tongue for the simultaneous analysis of phenols, sugars and organic acids in wines
Authors: Pettinelli Stefano , Pérez‐Gonzàlez Clara , Salvo‐Comino Coral , Mencarelli Fabio , Garcia‐Cabezón Cristina , Rodriguez‐Mendez Maria Luz
Published: November 2023

BACKGROUND

Electronic tongues have been widely used to analyze wines. However, owing to the complexity of the matrix, the problem is not completely solved and further improvements are required.

RESULTS

A high‐performance potentiometric bioelectronic tongue (bio‐ET) specifically devoted to the assessment of wine components is presented. The novelty of this system is due to two innovative approaches. First, the improved performance is obtained through the use of potentiometric biosensors based on carboxylated polyvinyl chloride (PVC) membranes, where enzymes (glucose oxidase, tyrosinase, laccase, and lyase) specific to compounds of interest are linked covalently. Second, the performance is further enhanced by introducing electron mediators (gold nanoparticles or copper phthalocyanine) into the PVC membrane to facilitate the electron transfer process. Individual sensors exposed to target analytes (glucose, catechol, cysteine, or tartaric acid) show a linear behavior, with limits of detection in the region of 10−4 mol L−1 for all the compounds analyzed, with excellent reproducibility (coefficient of variation lower than 3%). Sensors combined to form a bio‐ET show excellent capabilities. Principal component (PC) analysis can discriminate monovarietal white wines (PC1 77%; PC2 15%) and red wines (PC1 63%; PC2 30%). Using partial least squares, the bio‐ET can provide information about chemical parameters, including glucose, total polyphenols, total anthocyanins, free and total sulfur dioxide, total acidity, and pH with R2 between 0.91 and 0.98 in calibration and between 0.89 and 0.98 in validation.

CONCLUSIONS

This advanced instrument is able to assess the levels of seven parameters in a single measurement, providing an advantageous method to the wine industry. © 2023 Society of Chemical Industry.
Fabrication of dry S/O/W microcapsule and its probiotic protection against different stresses
Authors: Guo Qianwan , Cui Bo , Yuan Chao , Guo Li , Li Zhao , Chai Qingqing , Wang Na , Gänzle Michael , Zhao Meng
Published: November 2023

BACKGROUND

Encapsulation is commonly used to protect probiotics against harsh stresses. Thus, the fabrication of microcapsules with special structure is critical. In this work, microcapsules with the structure of S/O/W (solid‐in‐oil‐in‐water) emulsion were prepared for probiotics, with butterfat containing probiotics as the inner core and with whey protein isolate fibrils (WPIF) and antioxidants (epigallocatechin gallate, EGCG; glutathione, GSH) as the outer shell.

RESULTS

Based on the high viscosity and good emulsifying ability of WPIF, dry well‐dispersed microcapsules were successfully prepared via the stabilization of the butterfat emulsion during freeze‐drying with 30–50 g L−1 WPIF. WPIF, WPIF + EGCG, and WPIF + GSH microcapsules with 50 g L−1 WPIF protected probiotics very well against different stresses and exhibited similar inactivation results, indicating that EGCG and GSH exerted neither harm or protection on probiotics. This significantly reduced the harmful effects of antioxidants on probiotics. Almost all the probiotics survived after pasteurization, which was critical for the use of probiotics in other foods. The inactivation values of probiotics in microcapsules were around 1 log in simulated gastric juice (SGJ), about 0.5 log in simulated intestinal juice (SIJ), and around 1 log after 40 days of ambient storage.

CONCLUSION

Dry S/O/W microcapsule, with butterfat containing probiotics as the inner core and WPIF as the outer shell, significantly increased the resistance of probiotics to harsh environments. This work proposed a preparation method of dry S/O/W microcapsule with core/shell structure, which could be used in the encapsulation of probiotics and other bioactive ingredients.
Advances in Dynamic Light Scattering Imaging of Blood Flow
Authors: Sdobnov Anton , Piavchenko Gennadii , Bykov Alexander , Meglinski Igor
Published: November 2023

Dynamic light scattering (DLS) is a well known experimental approach uniquely suited for the characterization of small particles undergoing Brownian motion in randomly inhomogeneous turbid scattering medium, including water suspension, polymers in solutions, cells cultures, and so on. DLS is based on the illuminating of turbid medium with a coherent laser light and further analyzes the intensity fluctuations caused by the motion of the scattering particles. The DLS‐based spin‐off derivative techniques, such laser Doppler flowmetry (LDF), diffusing wave spectroscopy (DWS), laser speckle contrast imaging (LSCI), and Doppler optical coherence tomography (DOCT), are exploited widely for non‐invasive imaging of blood flow in brain, skin, muscles, and other biological tissues. The recent advancements in the DLS‐based imaging technologies in frame of their application for brain blood flow monitoring, skin perfusion measurements, and non‐invasive blood micro‐circulation characterization are overviewed. The fundamentals, breakthrough potential, and practical findings revealed by DLS‐based blood flow imaging studies, including the limitations and challenges of the approach such as movement artifacts, non‐ergodicity, and overcoming high scattering properties of studied medium, are also discussed. It is concluded that continued research and further technological advancements in DLS‐based imaging will pave the way for new exciting developments and insights into blood flow diagnostic imaging.
Biallelic COQ4 Variants in Hereditary Spastic Paraplegia: Clinical and Molecular Characterization
Authors: Lin Xiang , Jiang Jun‐Yi , Hong Dao‐jun , Lin Kai‐Jun , Li Jin‐Jing , Chen Yi‐Jun , Qiu Yu‐sen , Wang Zishuai , Liao Yi‐Chu , Yang Kang , Shi Yan , Wang Meng‐wen , Hsu Shao‐Lun , Hong Shunyan , Zeng Yi‐Heng , Chen Xiao‐Chun , Wang Ning , Lee Yi‐Chung , Chen Wan‐Jin
Published: November 2023

Background

Hereditary spastic paraplegias (HSP) are neurologic disorders characterized by progressive lower‐extremity spasticity. Despite the identification of several HSP‐related genes, many patients lack a genetic diagnosis.

Objectives

The aims were to confirm the pathogenic role of biallelic COQ4 mutations in HSP and elucidate the clinical, genetic, and functional molecular features of COQ4‐associated HSP.

Methods

Whole exome sequences of 310 index patients with HSP of unknown cause from three distinct populations were analyzed to identify potential HSP causal genes. Clinical data obtained from patients harboring candidate causal mutations were examined. Functional characterization of COQ4 variants was performed using bioinformatic tools, single‐cell RNA sequencing, biochemical assays in cell lines, primary fibroblasts, induced pluripotent stem cell–derived pyramidal neurons, and zebrafish.

Results

Compound heterozygous variants in COQ4, which cosegregated with HSP in pedigrees, were identified in 7 patients from six unrelated families. Patients from four of the six families presented with pure HSP, whereas probands of the other two families exhibited complicated HSP with epilepsy or with cerebellar ataxia. In patient‐derived fibroblasts and COQ4 knockout complementation lines, stable expression of these missense variants exerted loss‐of‐function effects, including mitochondrial reactive oxygen species accumulation, decreased mitochondrial membrane potential, and lower ubiquinone biosynthesis. Whereas differentiated pyramidal neurons expressed high COQ4 levels, coq4 knockdown zebrafish displayed severe motor dysfunction, reflecting motor neuron dysregulation.

Conclusions

Our study confirms that loss‐of‐function, compound heterozygous, pathogenic COQ4 variants are causal for autosomal recessive pure and complicated HSP. Moreover, reduced COQ4 levels attributable to variants correspond with decreased ubiquinone biosynthesis, impaired mitochondrial function, and higher phenotypic disease severity. © 2023 International Parkinson and Movement Disorder Society.
Progressive Cerebrovascular Reactivity Reduction Occurs in Parkinson's Disease: A Longitudinal Study
Authors: Wang Jian , Li Hongwei , Jia Jia , Shao Xiali , Li Yuanfang , Zhou Ying , Wang He , Jin Lirong
Published: November 2023

Background

The change of microvascular function over the course of Parkinson's disease (PD) remains unclear.

Objective

We aimed to ascertain regional cerebrovascular reactivity (CVR) changes in the patients with PD at baseline (V0) and during a 2‐year follow‐up period (V1). We further investigated whether alterations in CVR were linked to cognitive decline and brain functional connectivity (FC).

Methods

We recruited 90 PD patients and 51 matched healthy controls (HCs). PD patients underwent clinical evaluations, neuropsychological assessments, and magnetic resonance (MR) scanning at V0 and V1, whereas HCs completed neuropsychological assessments and MR at baseline. The analysis included evaluating CVR and FC maps derived from resting‐state functional magnetic resonance imaging and investigating CVR measurement reproducibility.

Results

Compared with HCs, CVR reduction in left inferior occipital gyrus and right superior temporal cortex at V0 persisted at V1, with larger clusters. Longitudinal reduction in CVR of the left posterior cingulate cortex correlated with decline in Trail Making Test B performance within PD patients. Reproducibility validation further confirmed these findings. In addition, the results also showed that there was a tendency for FC to be weakened from posterior to anterior with the progression of the disease.

Conclusions

Microvascular dysfunction might be involved in disease progression, subsequently weaken brain FC, and partly contribute to executive function deficits in early PD. © 2023 International Parkinson and Movement Disorder Society.
LSD1 in drug discovery: From biological function to clinical application
Authors: Liu Hui‐Min , Zhou Ying , Chen He‐Xiang , Wu Jiang‐Wan , Ji Shi‐Kun , Shen Liang , Wang Shao‐Peng , Liu Hong‐Min , Liu Ying , Dai Xing‐Jie , Zheng Yi‐Chao
Published: November 2023

Lysine‐specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD) dependent monoamine oxidase (MAO) that erases the mono‐, and dimethylation of histone 3 lysine 4 (H3K4), resulting in the suppression of target gene transcriptions. Besides, it can also demethylate some nonhistone substrates to regulate their biological functions. As reported, LSD1 is widely upregulated and plays a key role in several kinds of cancers, pharmacological or genetic ablation of LSD1 in cancer cells suppresses cell aggressiveness by several distinct mechanisms. Therefore, numerous LSD1 inhibitors, including covalent and noncovalent, have been developed and several of them have entered clinical trials. Herein, we systemically reviewed and discussed the biological function of LSD1 in tumors, lymphocytes as well as LSD1‐targeting inhibitors in clinical trials, hoping to benefit the field of LSD1 and its inhibitors.
Transient receptor potential ankyrin 1 channels in the bladder mediate low temperature elicited bladder overactivity in rats
Authors: Imamura Tetsuya , Ogawa Teruyuki , Minagawa Tomonori , Daimon Hironori , Nagai Takashi , Ueno Manabu , Saito Tetsuichi , Ishizuka Osamu
Published: November 2023

Aims

This study aimed to investigate whether pathways involving transient receptor potential ankyrin 1 (TRPA1) channels in the urinary bladder mediate the bladder overactivity elicited by exposure to a low temperature in rats.

Methods

At postnatal week 10, female Sprague–Dawley (SD) rats were intraperitoneally injected with the TRPA1 channel antagonist, HC030031, at room temperature (RT) and subsequently exposed to low temperature (LT). Bladder specimens treated with HC030031 were evaluated for contractions through cumulative addition of the TRPA1 channel agonist trans‐cinnamaldehyde. Two days before cystometric investigation, small interfering RNA (siRNA) targeting TRPA1 was transfected into urinary bladders. Then, cystometric investigations were performed on rats subjected to TRPA1 siRNA transfection at both RT and LT. Expression of TRPA1 channels in the urinary bladder was assessed through immunohistochemistry and real‐time reverse transcription‐polymerase chain reaction.

Results

At RT, micturition patterns were unaffected by HC030031 treatment. However, upon exposure to LT, rats treated with HC030031 exhibited a reduction of LT‐elicited bladder overactivity, as evidenced by inhibited decreases in voiding interval, micturition volume, and bladder capacity. Additionally, HC030031 inhibited trans‐cinnamaldehyde‐induced contractions. Immunohistochemical analysis showed the presence of TRPA1 channels in the urinary bladder. Notably, rats with TRPA1 siRNA‐transfected bladders could partially inhibit bladder overactivity during LT exposure.

Conclusions

These findings indicate that pathways involving TRPA1 channels expressed in the urinary bladder could mediate the LT‐elicited bladder overactivity.
Lower urinary tract symptoms in young‐middle aged males with a diagnosis of obstructive sleep apnea syndrome
Authors: Di Bello Francesco , Pezone Gabriele , Muzii Benedetta , Cilio Simone , Ruvolo Claudia Collà , Scandurra Cristiano , Mocini Edoardo , Creta Massimiliano , Morra Simone , Bochicchio Vincenzo , Salzano Giovanni , Vaira Luigi Angelo , Mangiapia Francesco , Motta Gaetano , Maldonato Nelson Mauro , Longo Nicola , Cantone Elena , Califano Gianluigi
Published: November 2023

Background

The aim of the current study is to measure the prevalence and the potential role of International Prostate Symptom Score (IPSS) score as a predictor of obstructive sleep apnea syndrome (OSAS) in male experienced lower urinary tract symptoms (LUTS).

Methods

A cross‐sectional web‐based Italian survey was administered via Google Forms between July 17 and October 31, 2022. The urinary functioning was measured through the IPSS questionnaire. Specifically, we considered symptoms occurring more than “about half the time” (score ≥ 3) as bothering symptoms. Multivariable logistic regression models (LRMs) adjusting for age, body mass index (BMI), International Index of Erectile Function‐5, IPSS, and hypertension were fitted to predict OSAS in the cohort of men responding to the survey and experiencing LUTS.

Results

Overall, 58 (24.4%) patients had a confirmed diagnosis of OSAS. The overall median IPSS was 5 (inter quartile range [IQR]: 3–8), respectively. According to IPSS items, 24 (10%), 44 (18.4%), 12 (5%), 12 (5%), 12 (5%), 11 (4.6%), 63 (26.4%) patients exhibit incomplete bladder emptying, urinary frequency, intermittency, urgency, weak stream, straining, nocturia with a score ≥ 3, respectively. After multivariable LRMs predicting the developing OSAS, age (odds ratio [OR]: 1.09, p < 0.001), BMI (OR:1.12, p < 0.001) and IPSS total score (OR:1.08, p = 0.02) were independent predicting factors.

Conclusion

This analysis revealed that the IPSS total score, age, and BMI are independent predictors of OSAS in males. In this context, the use of IPSS in daily practice could be helpful in assessing the LUTS presence and in supporting physicians to identify a hidden sleep apnea condition.
Gamma‐band harmonic responses for beta‐band auditory steady‐state response are intact in patients with early stage schizophrenia
Authors: Tada Mariko , Kirihara Kenji , Nagai Tatsuya , Koike Shinsuke , Araki Tsuyoshi , Kasai Kiyoto
Published: November 2023

Gamma oscillations, thought to arise from the activity of ɣ‐aminobutyric acid (GABA)ergic interneurons, have potential as a biomarker for schizophrenia. Gamma‐band auditory steady‐state responses (ASSRs) are notably reduced in both chronic and early‐stage schizophrenia patients. Furthermore, alterations in gamma‐band ASSRs have been demonstrated in animal models through translational research. However, the 40‐Hz harmonic responses of the 20‐Hz ASSR are not as well‐characterized, despite the possibility that these harmonic oscillatory responses may reflect resonant activity in neural circuits. In this study, we investigated the 40‐Hz harmonic response to the 20‐Hz ASSR in the early stages of schizophrenia. The study recruited 49 participants, including 15 individuals at ultra‐high‐risk (UHR) for psychosis, 13 patients with first‐episode schizophrenia (FES), and 21 healthy controls (HCs). The 40‐Hz harmonic responses of the 20‐Hz ASSR were evident in all groups. Interestingly, while previous report observed reduced 40‐Hz ASSRs, the 40‐Hz harmonic responses of the 20‐Hz ASSR were not reduced in the UHR or FES groups. These findings suggest that the gamma‐band ASSR and its harmonic responses may represent distinct aspects of pathophysiology in the early stages of schizophrenia.
Growing up in the suburbs: Growth faltering and disease burden in the children from 16th to 18th century Tallinn, Estonia
Authors: Vilumets Linda , Aguraiuja‐Lätti Ülle , Lewis Mary
Published: November 2023

This paper presents the results of the first large‐scale study of children from early modern northern Estonia. A total of 191 non‐adults (<17 years) from the 16th–18th century Tõnismägi cemetery in the suburbs of Tallinn were analyzed to gain a better understanding of the health and living environment of these low‐status children. This was achieved through growth analysis and palaeopathological investigation of metabolic and respiratory diseases such as scurvy, vitamin D deficiency, and tuberculosis. Growth disruption was shown to be the most severe among non‐adults aged between 4 and 9 years and comparable to children living in post‐medieval London. It is unlikely that the children from Tallinn would have experienced the same level of industrial hazards as those in London, but poor socioeconomic status, an impoverished diet, and unsanitary living conditions in the suburbs had a detrimental effect on the growth of these non‐adults. This was supported by a statistically significant correlation between growth faltering and respiratory infections and evidence for scurvy in 40% of the infants (n = 30). The most likely cause was early weaning and a diet devoid of vitamin C, induced by poverty and cultural practices. The prevalence of rickets was much lower when compared with other post‐medieval populations in Europe, at just 1.2%. This suggests that children living in Tallinn were not deprived of sunlight and may have had access to more green spaces.
Surface functionalization of carbon fiber by hydrothermally synthesized ZnO nanostructures for mechanical strengthening of polymer composites
Authors: Rai Ravi Shankar , Bajpai Vivek
Published: November 2023

In this work, the effects of ZnO nanostructure‐surface functionalized carbon fibers has been examined along with their impacts on mechanical attributes of resulting hybrid carbon fiber reinforced polymer (CFRP) composites. The procedure involves hydrothermally generating ZnO nanostructures on carbon fibers. To generate hybrid composites, the modified carbon fiber fabric is then utilized as reinforcement in a matrix made of bisphenol‐A epoxy resin and polymer. The electron microscopy technique was employed to study development phenomenon of nanostructures on the fiber. According to the findings, lengthening the growth treatment and increasing seeding cycles improves the rate of ZnO formation. However, the results are not significantly impacted by the growth solution's concentration. The weight change analysis, X‐ray diffraction, Fourier transform infrared spectroscopy, UV‐spectroscopy, and energy dispersive spectroscopy all provide additional support for these conclusions. In comparison to plain CFRP composites, the developed hybrid CFRP composites tensile properties and impact resistance are significantly better. The ZnO‐modified CFRP composites exhibit improvements in elastic modulus, tensile strength, and in‐plane shear strength of up to 46.44%, 48.63%, and 20.79%, respectively. The hybrid composites' capacity to absorb impact energy also rises by 76%. Based on these results, the developed hybrid composites exhibit promising properties for applications in industries such as aircraft and automobile manufacturing. They offer high impact strength, high modulus, lightweight characteristics, and low void content, making them desirable materials for these industries.

Highlights

Controlled growth of vertically aligned ZnO nanostructures on fiber surface has been accomplished using hydrothermal method.

Characteristics of CFRP composites such as tensile strength, elastic modulus, in‐plane shear strength, and impact energy absorption, were significantly enhanced on inclusion of ZnO.

The developed hybrid composites offer cost‐effective solutions with improved mechanical properties.

High impact strength and modulus make them suitable for applications in aircraft and automobile industries.

Achieved exceptional morphological structure and enhanced surface‐to‐volume ratio.
Design of dual‐conductive polyacrylonitrile‐based composite nanofiber: Synergistic effect of copper nanoparticles decorated‐boron nitride and polyaniline
Authors: Orhun Zümer , Doğan Deniz , Erdem Ümit , Yıldırım Gürcan , Pehlivanlı Zühtü Onur , Metin Ayşegül Ülkü
Published: November 2023

Conductive composite nanofibers are promising materials, especially wearable strain sensors, due to their lightweight, breathability, flexibility, and skin affinity. Here, we propose a dual‐conductive network by the sequential decoration of amin‐modified boron nitride nanosheets (BN), copper nanoparticles (Cu), and polyaniline (PANI) into the elastic thermoplastic polyacrylonitrile (PAN) nanofiber. The Cu nanoparticles/BN‐enwrapped PANI nanocomposite was synthesized using successive environmentally friendly reduction and chemical oxidation polymerization. First, Cu (II) ions were immobilized on modified BN and reduced with L‐ascorbic acid (BN@Cu), followed by a chemical oxidation polymerization of aniline using ammonium persulfate as an initiator (BN@Cu/PANI). The XRD (X‐ray diffraction), FTIR (Fourier Transform Infrared Spectroscopy), SEM (Scanning Electron Microscopy), and TEM/EDXS (Transmission Electron Microscopy/Energy Dispersive X‐ray Spectroscopy) analysis confirmed the coexistence of the BN@Cu/PANI phase and composition. The DC electrical conductivity of BN@Cu/PANI nanocomposite (0.567 S/cm) was quietly higher than PANI (0.167 S/cm) and BN@Cu (0.077 S/cm). The thermal conductivity of BN@Cu and BN@Cu/PANI was 0.626 and 0.444 W/mK, respectively. The BN@Cu/PANI loaded‐PAN composite nanofibers were successfully produced by electrospinning. SEM studies confirmed that the composite nanofibers have uniform fiber structure and suitable BN@Cu/PANI dispersion/distribution within the PAN. BN@Cu/PANI‐reinforced PAN nanofibers showed a 2‐fold decrease in the specific heat capacity and a 50‐fold increase in electrical conductivity of the nanofibers at 10 wt%BN@Cu/PANI loading. This work offers dual‐conductive polymer‐based composites, which can be used in thermal management applications in microelectronics devices.

Highlights

The dual‐conductive nanocomposite, BN@Cu/PANI, was prepared a simple, low‐cost method.

BN@Cu/PANI, core/shell nanocomposite, was easily produced this way for the first time.

BN@Cu nanoparticles increased the polymerization rate of PANI.

The thermal and electrical conductivity of BN@Cu/PANI was 0.444 W/mK and 0.567 S/cm.

Electrical conductivity of BN@Cu/PANI‐PAN increased 50‐fold increase at 10 wt%BN@Cu/PANI.
Prenatal diagnosis of Hartsfield syndrome with a novel genetic variant
Authors: Rich Matthew , Schroeder Bradley , Manning Courtney , Abbott Mary‐Alice
Published: November 2023

A G2P0, 24‐year‐old woman presented at 17 weeks 3 days gestation for a fetal anatomy scan. Ultrasound identified bilateral upper and lower extremity ectrodactyly, semilobar holoprosencephaly, midface hypoplasia, and cleft lip and palate. Amniocentesis for a chromosome microarray demonstrated no significant copy number changes. Whole exome sequencing was subsequently completed, which revealed a de novo, likely pathogenic variant in FGFR1, c.2044G>A (D682N), consistent with FGFR1‐related Hartsfield syndrome. This case highlights the first presumed molecularly confirmed prenatal diagnosis of Hartsfield syndrome and identifies a new pathogenic variant.
Cellular control of protein levels: A systems biology perspective
Authors: Munro Victoria , Kelly Van , Messner Christoph B. , Kustatscher Georg
Published: November 2023

How cells regulate protein levels is a central question of biology. Over the past decades, molecular biology research has provided profound insights into the mechanisms and the molecular machinery governing each step of the gene expression process, from transcription to protein degradation. Recent advances in transcriptomics and proteomics have complemented our understanding of these fundamental cellular processes with a quantitative, systems‐level perspective. Multi‐omic studies revealed significant quantitative, kinetic and functional differences between the genome, transcriptome and proteome. While protein levels often correlate with mRNA levels, quantitative investigations have demonstrated a substantial impact of translation and protein degradation on protein expression control. In addition, protein‐level regulation appears to play a crucial role in buffering protein abundances against undesirable mRNA expression variation. These findings have practical implications for many fields, including gene function prediction and precision medicine.
Trends in bronchopulmonary dysplasia and respiratory support among extremely preterm infants in China over a decade
Authors: Zhu Zhicheng , He Yue , Yuan Lin , Chen Liping , Yu Yonghui , Liu Ling , Sun Huiqing , Xu Liping , Wei Qiufen , Cui Shudong , Lai Chunhua , Zhang Juan , Tan Yuan , Yu Xinqiao , Jiang Chunming , Chen Chao
Published: November 2023

Objective

Bronchopulmonary dysplasia (BPD) is one of the most serious complications affecting extremely preterm infants. We aimed to evaluate temporal trends in BPD and administration of respiratory support among extremely preterm infants in China over a decade.

Methods

This was a retrospective study using data from a multicenter database, which included infants born less than 28 weeks' gestation discharged from 68 tertiary neonatal care centers in China between 2010 and 2019. Changes in rates and severity of BPD, as well as modalities and duration of respiratory support, were evaluated.

Results

Among 4808 eligible infants with gestational age (GA) of 21+6/7 to 27+6/7 weeks and a mean (SD) birth weight of 980 (177) g, no significant change of median GA was found over time. Overall, 780 (16.2%) infants died before 36 weeks' postmenstrual age, 2415 (50.2%) were classified as having no BPD, 917 (19.1%) developed Grade 1 BPD, 578 (12.0%) developed Grade 2 BPD, and 118 (2.5%) developed Grade 3 BPD. The rate of BPD increased from 20.8% in 2010 to 40.7% in 2019 (aRR for trend, 1.081; 95% confidence interval, 1.062–1.099), especially for Grade 1 and Grade 2. Although survival to discharge improved over the decade, the overall survival without BPD did not change during the study period. The use of invasive mechanical ventilation (IMV) remained unchanged. However, the use of noninvasive ventilation (NIV) increased from 71.5% in 2010 to 89.8% in 2019. Moreover, the median duration of NIV increased over time, from 17.0 (4.8, 34.0) days in 2010 to 33.0 (21.0, 44.0) days in 2019, without significant change in the duration of IMV.

Conclusions

Although survival increased over the decade and respiratory support practices changed significantly between 2010 and 2019 in China, with increased use and duration of NIV, there was an increased rate of BPD and survival without BPD has not improved.
A systematic review of antimicrobial therapy in children with tracheostomies
Authors: Pearce Helen , Talks Benjamin James , Powell Steven , Brodlie Malcolm , Powell Jason
Published: November 2023

Tracheostomies are indicated in children to facilitate long‐term ventilatory support, aid in the management of secretions, or manage upper airway obstruction. Children with tracheostomies often experience ongoing airway complications, of which respiratory tract infections are common. They subsequently receive frequent courses of broad‐spectrum antimicrobials for the prevention or treatment of respiratory tract infections. However, there is little consensus in practice with regard to the indication for treatment/prophylactic antimicrobial use, choice of antimicrobial, route of administration, or duration of treatment between different centers. Routine antibiotic use is associated with adverse effects and an increased risk of antimicrobial resistance. Tracheal cultures are commonly obtained from pediatric tracheostomy patients, with the aim of helping guide antimicrobial therapy choice. However, a positive culture alone is not diagnostic of infection and the role of routine surveillance cultures remains contentious. Inhaled antimicrobial use is also widespread in the management of tracheostomy‐associated infections; this is largely based on the theoretical benefits of higher airway antibiotic concentrations. The role of prophylactic inhaled antimicrobial use for tracheostomy‐associated infections remains largely unproven. This systematic review summarizes the current evidence base for antimicrobial selection, duration, and administration route in pediatric tracheostomy‐associated infections. It also highlights significant variation in practice between centers and the urgent need for further prospective evidence to guide the management of these vulnerable patients.
The migrant perspective: Measuring migrants' movements and interests using geolocated tweets
Authors: Mast Johannes , Sapena Marta , Mühlbauer Martin , Biewer Carolin , Taubenböck Hannes
Published: November 2023

Geolocated social media data hold a hitherto untapped potential for exploring the relationship between user mobility and their interests at a large scale. Using geolocated Twitter data from Nigeria, we provide a feasibility study that demonstrates how the linkage of (1) a trajectory analysis of Twitter users' geolocation and (2) natural language processing of Twitter users' text content can reveal information about the interests of migrants. After identifying migrants via a trajectory analysis, we train a language model to automatically detect the topics of the migrants' tweets. Biases of manual labelling are circumvented by learning community‐defined topics from a Nigerian web forum. Results suggest that differences in users' mobility correlate with varying interests in several topics, most notably religion. We find that Twitter data can be a flexible source for exploring the link between users' mobility and interests in large‐scale analyses of urban populations. The joint use of spatial techniques and text analysis enables migration researchers to (a) study migrant perspectives in greater detail than is possible with census data and (b) at a larger scale than is feasible with interviews. Thereby, it provides a valuable complement to interviews, surveys and censuses, and holds a large potential for further research.
Thermal Conductivity of MoS2 and Graphene/MoS2 Heterojunction
Authors: Zhan Qicai , Fu Zhao , Zhong Xiangli , Song Hongjia , Wang Jinbin
Published: November 2023

With the development of the miniaturization of electronic devices, controlling heat dissipation has become a key factor, which affects the service life of devices and energy utilization efficiency. Therefore, it is particularly important to study the heat conduction mechanism of nanomaterials inside microelectronic devices. Herein, the thermal conductivity of MoS2 and graphene/MoS2 heterojunctions using the bond‐order–length–strength theory and the local bond average method is quantitatively analyzed; the functional relationship between the thermal conductivity and the number of layers, temperature, and pressure is established; and the variation trend of thermal conductivity of materials with these factors is studied. The results show that the thermal conductivity of MoS2 and graphene/MoS2 heterojunctions is inversely proportional to the number of layers and temperature, proportional to the pressure. The work provides a simple and effective method for the study of thermal transport properties of 2D materials and heterojunction systems from the perspective of chemical bonding changes at the atomic level.