bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune-related ureteritis and cystitis induced by immune checkpoint inhibitors: Case report and literature review
Authors: Li Jun , Yu Ya-Fen , Qi Xiao-Wei , Du Yuan , Li Chun-Qing
Published: January 2023

Immune checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA4) and anti-programmed death cell protein 1 (anti-PD-1), are increasingly prescribed in metastatic carcinoma therapy. ICI-related kidney injury is gradually recognized by clinicians. However, immune-related ureteritis and cystitis easily go undiagnosed. We report three cases of PD-1 monoclonal antibody (mAb)-related ureteritis and cystitis. We further carried out a review of the literature about ICI-related ureteritis and cystitis. The cases in our reports manifest urinary irritation, sterile pyuria, gross hematuria, hydronephrosis, dilation of the ureters, and acute kidney injury. Urinary irritation improved effectively; urinalysis and renal function returned to normal after glucocorticoid therapy. During ICI therapy, urinalysis and renal function and urinary imaging examination are recommended to be monitored regularly. It contributes to identify immune-related ureteritis/cystitis earlier to efficiently alleviate urinary symptoms and immunologic urinary tract injury through glucocorticoid therapy while avoiding the abuse of antibiotics.
CCL2: An important cytokine in normal and pathological pregnancies: A review
Authors: Lin Zhi , Shi Jia-Lu , Chen Min , Zheng Zi-Meng , Li Ming-Qing , Shao Jun
Published: January 2023

C-C motif ligand 2 (CCL2), also known as monocytic chemotactic protein 1 (MCP-1), is an integral chemotactic factor which recruits macrophages for the immune response. Together with its receptors (e.g., CCR2, ACKR1, and ACKR2), they exert noticeable influences on various diseases of different systems. At the maternal-fetal interface, CCL2 is detected to be expressed in trophoblasts, decidual tissue, the myometrium, and others. Meanwhile, existing reports have determined a series of physiological regulators of CCL2, which functions in maintaining normal recruitment of immunocytes, tissue remodeling, and angiogenesis. However, abnormal levels of CCL2 have also been reported to be associated with adverse pregnancy outcomes such as spontaneous abortion, preeclampsia and preterm labor. In this review, we concentrate on CCL2 expression at the maternal-fetal interface, as well as its precise regulatory mechanisms and classic signaling pathways, to reveal the multidimensional aspects of CCL2 in pregnancy.
Single-cell transcriptomics reveals striking heterogeneity and functional organization of dendritic and monocytic cells in the bovine mesenteric lymph node
Authors: Barut Güliz Tuba , Kreuzer Marco , Bruggmann Rémy , Summerfield Artur , Talker Stephanie C.
Published: January 2023

Dendritic and monocytic cells co-operate to initiate and shape adaptive immune responses in secondary lymphoid tissue. The complexity of this system is poorly understood, also because of the high phenotypic and functional plasticity of monocytic cells. We have sequenced mononuclear phagocytes in mesenteric lymph nodes (LN) of three adult cows at the single-cell level, revealing ten dendritic-cell (DC) clusters and seven monocyte/macrophage clusters with clearly distinct transcriptomic profiles. Among DC, we defined LN-resident subsets and their progenitors, as well as subsets of highly activated migratory DC differing in transcript levels for T-cell attracting chemokines. Our analyses also revealed a potential differentiation path for cDC2, resulting in a cluster of inflammatory cDC2 with close transcriptional similarity to putative DC3 and monocyte-derived DC. Monocytes and macrophages displayed sub-clustering mainly driven by pro- or anti-inflammatory expression signatures, including a small cluster of cycling, presumably self-renewing, macrophages. With this transcriptomic snapshot of LN-derived mononuclear phagocytes, we reveal functional properties and differentiation trajectories in a “command center of immunity”, and identify elements that are conserved across species.
China’s choice on the participation in establishing marine protected areas in areas beyond national jurisdiction
Authors: Yu Minyou , Huang Yuwen
Published: January 2023

Currently, the issue of marine biodiversity in areas beyond national jurisdiction (ABNJ) has made a lot of significant progress in both international legislative process and national practices. As a State Party to UNCLOS, China has actively participated in the negotiations of the BBNJ agreement, in which the marine protected areas (MPAs) as one of the area-based management tools have been an issue of great concern. It is considered to be a feasible and direct conservation tool. In order to evaluate the possibility of China’s participation in the establishment of MPAs in the future, this paper analyzes the drivers for and limits on China’s involvement in the construction of MPAs in the context of the current Chinese situation. And it also puts forward possible countermeasures on how to deal with the challenges brought by the MPAs in ABNJ to China. It is concluded that there is a great possibility that China will eventually choose to participate in the establishment of MPAs in ABNJ as China advocates the concept of a maritime community with a shared future.
Protective effect of Sargassum fusiforme polysaccharides on H2O2-induced injury in LO2 cells
Authors: Li Jiarui , Wang Zhuo , Chen Jianping , Luo Baozhen , Chen Xuehua , Li Rui , Gao Jialong , Liu Xiaofei , Song Bingbing , Zhong Saiyi
Published: January 2023

Introduction

Sargassum fusiform is considered a traditional Chinese medicinal herb to treat many diseases, Sargassum fusiform polysaccharides (SFPS) were found to display many important biological activities. The purpose of this study was to investigate the in vitro antioxidant activity of crude polysaccharide from Sargassum fusiforme and its protective effect against H2O2-induced injury in LO2 cells.

Methods

SFPS was extracted from Sargassum fusiforme using water extraction and alcohol precipitation. High-performance liquid chromatography (HPLC) was used to measure its monosaccharide composition. The in vitro antioxidant activity of SFPS was evaluated using scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical assays. Moreover, its hepatoprotective activity was examined by establishing H2O2-induced LO2 cells injury model.

Results and discussion

The results showed that the SFPS was composed of Glc, Ara, Fuc, Gal, Man, Rha and Xyl. Meanwhile, SFPS exhibited strong antioxidant activity and potential hepatoprotective effect. Further studies found that SFPS could alleviate LO2 cells injury induced by H2O2 via decreasing malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels, increasing superoxide dismutase (SOD) and catalase (CAT) activities and inhibiting intracellular reactive oxygen species (ROS) production. These results revealed that SFPS had the ability to protect the liver cells from H2O2-induced liver injury through its antioxidant activity.
Calculation model of concrete-filled steel tube arch bridges based on the “arch effect”
Authors: Wang Shaorui , Li Yingbin , Liu Zengwu , Cheng Tianlei
Published: January 2023

In view of the limitations of the current code based on the equivalent beam-column method with the “rod mode” instead of the “arch mode” for the calculation of concrete-filled steel tube arch bridges, this paper takes the real bearing mechanism of the arch as the starting point and analyzes the different bearing mechanisms of the arch and eccentric pressurized column. The concrete-filled steel tube arch model test was carried out to analyze the deformation state and damage mode, and the geometric non-linear bending moment of the measured arch was compared with the bending moment value calculated by the eccentricity increase coefficient of the “rod mode.” The results showed that the transfer of internal force is from the axial force to the arch axis, causing the vertical reaction force and horizontal thrust. However, the eccentric compression column only produced the vertical force at the bottom and combines with the lateral deformation indirectly generated by the eccentric distance. In addition, the deformation stage of the arch is basically the same as that of the eccentric compression column. The final failure mode of the arch is 4-hinge damage, and the final failure mode of the eccentric compression column is single-hinge damage. The preliminary geometric non-linear bending moment value obtained by the two modes accords well. Therefore, the main factors for the difference in the bearing mechanism between the two modes are different force structures, force transmission routes, and sources of deformation. Due to the difference in the bearing mechanism, the final failure mode is different, and the deformation ability of the arch is weakened by using the “rod mode” instead of the “arch mode.” The geometric non-linear bending moment of the control section calculated by the eccentricity increase coefficient is conservative, but the influence of the geometric non-linearity of other sections is not considered enough.
Surface modification study of CaO-Al2O3-SiO2-Fe2O3 base system high temperature phase reconstruction
Authors: Yang Huanyin , Guo Hongli , Sun Hongjuan , Peng Tongjiang
Published: January 2023

The fly ash was used as raw material to prepare glass ceramic base body, on which a layer of glaze slurry was applied, then, the complex was successfully prepared by sintering at 1180 °C through single-sinter process. Influences of quartz sand content on crystal phase evolution, physical–mechanical properties, and surface morphology of products were studied systematically. Finally, an opaque glaze with 15 wt% quartz sand fitting on glass ceramic base body had been produced, exhibiting a unique main phase, mullite, which ensured a significant Vickers microhardness of 8.1 GPa, improving the mechanical properties of solid waste glass ceramic base body. It was also found that the water absorption of the product was .66%, which greatly enhanced the waterproof function of the base surface. The complex products developed in this study were expected to be used as building decoration materials and provided new ideas for effective reuse of other similar solid wastes.
Atomistic tensile deformation mechanisms in a CrCoNi medium-entropy alloy with gradient nano-grained structure at cryogenic temperature
Authors: Tao Yuhao , Cheng Wenqiang , Wang Wei
Published: January 2023

Large-scale molecular dynamics (MD) simulations have been utilized to reveal the atomistic deformation mechanisms of a CrCoNi medium-entropy alloy (MEA) with gradient nano-grained (GNG) structure in the present study. Strong strain hardening was observed in the gradient nano-grained structure at the elasto-plastic transition stage, which could be attributed to the Masing hardening. After yielding, obvious partitioning of tensile strain was detected in the gradient nano-grained structure, which indicates the existence of hetero-deformation induced (HDI) hardening effect and could account for the higher flow stress of the gradient nano-grained structure than that calculated by the rule of mixture from its homogenous nano-grained (NG) structured counterparts. Moreover, partitioning of stacking fault factor (corresponding to the partitioning of tensile strain), which demonstrates the intensity of dislocation behaviors, was also observed in the gradient nano-grained structure. The differences of factors for each grain size area were found to be smaller in the gradient nano-grained structure than those of its homogeneous nano-grained structured counterparts, which indicates the influence of forward stress and back stress on dislocation motion near the zone boundary between the hard zone with smaller grains and the soft zone with larger grains, further verifying the presence of hetero-deformation induced hardening in the gradient nano-grained structure.
Impact of tumor necrosis factor antagonist combination and anti-integrin therapies on body mass index in inflammatory bowel disease: A cross-sectional study
Authors: Shehab Mohammad , Alali Ali , Al-Hindawi Ahmed , Alsayegh Abdulwahab , Aldallal Usama , Abdullah Israa , Albaghli Abbas , Alrashed Fatema , Alfadhli Ahmad , Bessissow Talat
Published: January 2023

Background

The impact of biologic therapies on body mass index (BMI) in patients with inflammatory bowel disease (IBD) is unclear. This study investigates any associations between BMI, type of IBD, and the type of medications taken among patients with IBD with varying weight categories.

Methods

A cross sectional study was performed in an IBD tertiary care center. Data was obtained from patients with IBD attending outpatient clinics from January 1st, 2021 until November 1st, 2021. Adult patients, older than 18 years, with a diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) were recruited. The primary outcome was the association between BMI and medication used in IBD. The secondary outcome was the association between BMI and disease type and location in patients with IBD.

Results

The study included a total of 528 patients of which, 66.5% have CD. Patients with normal weight comprises 55.9% of the participants, while those who are underweight, overweight or obese are 3.4, 28.2, and 12.5%, respectively. None of the underweight patients had UC. Among the normal weight, overweight and obese BMI categories, 34.6% vs. 36.2% vs. 31.8% had UC, respectively. Patients who are on tumor necrosis factor inhibitors (anti-TNF) with an immunomodulator (anti-TNF combination), are more likely to be overweight or obese than patients who are not on anti-TNF combination (OR 2.86, 95% CI 1.739–4.711, p < 0.001). Patients on vedolizumab are twice as likely to be overweight or obese than patients not on vedolizumab (OR 2.23, 95% CI 1.086–4.584, p < 0.05). Patients with ileocolonic CD are more likely to be overweight or obese compared to other subtypes of CD (OR 1.78, 95% CI 1.14–2.77, p = 0.01).

Conclusion

Many patients with IBD are either obese or overweight. Patients with IBD who are on anti-TNF combination therapy or vedolizumab monotherapy are more likely to be obese and overweight. In addition, patients will ileocolonic CD are more likely to be obese or overweight.
Astatine-211 based radionuclide therapy: Current clinical trial landscape
Authors: Albertsson Per , Bäck Tom , Bergmark Karin , Hallqvist Andreas , Johansson Mia , Aneheim Emma , Lindegren Sture , Timperanza Chiara , Smerud Knut , Palm Stig
Published: January 2023

Astatine-211 (211At) has physical properties that make it one of the top candidates for use as a radiation source for alpha particle-based radionuclide therapy, also referred to as targeted alpha therapy (TAT). Here, we summarize the main results of the completed clinical trials, further describe ongoing trials, and discuss future prospects.
Norwegian society of rheumatology recommendations on diagnosis and treatment of patients with giant cell arteritis
Authors: Haaversen Anne Bull , Brekke Lene Kristin , Bakland Gunnstein , Rødevand Erik , Myklebust Geirmund , Diamantopoulos Andreas P.
Published: January 2023

Objective

To provide clinical guidance to Norwegian Rheumatologists and other clinicians involved in diagnosing and treating patients with giant cell arteritis (GCA).

Methods

The available evidence in the field was reviewed, and the GCA working group wrote draft guidelines. These guidelines were discussed and revised according to standard procedures within the Norwegian Society of Rheumatology. The European Alliance of Associations for Rheumatology (EULAR) recommendations for imaging and treatment in large vessel vasculitis and the British Society for Rheumatology (BSR) guidelines for diagnostics and treatment in GCA informed the development of the current guidelines.

Results

A total of 13 recommendations were developed. Ultrasound is recommended as the primary diagnostic test. In patients with suspected GCA, treatment with high doses of Prednisolone (40–60 mg) should be initiated immediately. For patients with refractory disease or relapse, Methotrexate (MTX) should be used as the first-line adjunctive therapy, followed by tocilizumab (TCZ).

Conclusion

Norwegian recommendations for diagnostics and treatment to improve management and outcome in patients with GCA were developed.
Successful hepatic resection for invasive Klebsiella pneumoniae large multiloculated liver abscesses with percutaneous drainage failure: A case report
Authors: Nojima Hiroyuki , Shimizu Hiroaki , Murakami Takashi , Yamazaki Masato , Yamazaki Kazuto , Suzuki Seiya , Shuto Kiyohiko , Kosugi Chihiro , Usui Akihiro , Koda Keiji
Published: January 2023

Background

Invasive Klebsiella-associated liver abscesses can progress rapidly and cause severe metastatic infections such as meningitis and hydrocephalus, which are associated with high morbidity and mortality. In patients with large multiloculated liver abscesses after failure of percutaneous drainage, rapid diagnosis of the abscess followed by hepatic resection is necessary for early recovery and to prevent severe secondary metastatic complications.

Case presentation

An 84-year-old woman with a large liver abscess and in septic shock was transferred to our hospital. Abdominal CT showed multiloculated liver abscesses 15 cm in diameter in the right lobe of the liver. We first performed percutaneous liver abscess drainage. The patient was managed in the intensive care unit, as well as treated with intravenous administration of meropenem followed by cefozopran according to the antibiogram. Klebsiella pneumoniae with invasive infection was confirmed by a string test in an isolated colony of K. pneumoniae; the K1 serotype with the rmpA and magA genes was determined by polymerase chain reaction and Sanger sequencing. Additional percutaneous liver abscess drainage was performed due to initial inadequate drainage. Although the abscess had shrunk to a diameter of 8 cm after drainage in 4 weeks, the patient recovered from sepsis, but still had low-grade fever (occasionally 38°C) and continued to have symptoms of chronic inflammation with persistent hyper mucus discharge from the liver abscess. Surgical resection was chosen to prevent prolonged hospitalization and ensure early recovery. A right posterior sectionectomy of the liver, including liver abscess, was performed. The post-operative course was uneventful, with no complications, and she was discharged after 18 days. There were no signs of abscess recurrence 1 year after surgery.

Conclusion

We present a case of successful hepatic resection after percutaneous drainage failure in a patient with invasive K. pneumoniae multiloculated liver abscess.
Integrating data from spontaneous and induced trans-10 shift of ruminal biohydrogenation reveals discriminant bacterial community changes at the OTU level
Authors: Enjalbert Francis , Zened Asma , Cauquil Laurent , Meynadier Annabelle
Published: January 2023

Introduction

Microbial digestion is of key importance for ruminants, and disturbances can affect efficiency and quality of products for human consumers. Ruminal biohydrogenation of dietary unsaturated fatty acids leads to a wide variety of specific fatty acids. Some dietary conditions can affect the pathways of this transformation, leading to trans-10 fatty acids rather than the more usual trans-11 fatty acids, this change resulting in milk fat depression in dairy cows.

Materials and methods

We combined data from an induced and spontaneous trans-10 shift of ruminal biohydrogenation, providing new insight on bacterial changes at different taxonomic levels. A trans-10 shift was induced using dietary addition of concentrate and/or unsaturated fat, and the spontaneous milk fat depression was observed in a commercial dairy herd.

Results and discussion

Most changes of microbial community related to bacteria that are not known to be involved in the biohydrogenation process, suggesting that the trans-10 shift may represent the biochemical marker of a wide change of bacterial community. At OTU level, sparse discriminant analysis revealed strong associations between this change of biohydrogenation pathway and some taxa, especially three taxa belonging to [Eubacterium] coprostanoligenes group, Muribaculaceae and Lachnospiraceae NK3A20 group, that could both be microbial markers of this disturbance and candidates for studies relative to their ability to produce trans-10 fatty acids.
Multiple mosquito AMPs are needed to potentiate their antifungal effect against entomopathogenic fungi
Authors: Ramirez José L. , Hampton Kylie J. , Rosales Alayna M. , Muturi Ephantus J.
Published: January 2023

Mosquito resistance to microbial infections, including fungal entomopathogens that are selected for mosquito control, depend on a range of antimicrobial effectors, among them antimicrobial peptides (AMPs). These short peptides, along the antimicrobial effector lysozyme, act by disrupting the microbial cell membrane or by interfering with microbial physiological processes. While the induction of AMPs and lysozyme during fungal entomopathogenic infections have been reported, their contribution to the mosquito antifungal response has not been evaluated. In this study, we assessed the induction of Ae. aegypti AMPs and lysozyme genes at two points of infection and against distinct entomopathogenic fungi. Our results indicate that fungal infection elicits the expression of cecropin, defensin, diptericin, holotricin, and lysozyme, but do not affect those of attacin or gambicin. We further evaluated the role of these antimicrobial effectors via RNAi-based depletion of select AMPs during challenges with two entomopathogenic fungi. Our results reveal that AMPs and lysozyme are critical to the antifungal response, acting in concert, rather than individually, to potentiate their antimicrobial effect against entomopathogenic fungi. This study further contributes to a better understanding of the mechanisms that confer resistance to entomopathogenic fungi in an important mosquito vector.
Proteiniphilum and Methanothrix harundinacea became dominant acetate utilizers in a methanogenic reactor operated under strong ammonia stress
Authors: Feng Gao , Zeng Yan , Wang Hui-Zhong , Chen Ya-Ting , Tang Yue-Qin
Published: January 2023

Microorganisms in anaerobic digestion (AD) are easily affected by ammonia, especially acetoclastic methanogens. Thus, in ammonia-suppressed AD systems, acetate degradation is reported to be carried out mainly by the cooperation of syntrophic acetate oxidizers and hydrogenotrophic methanogens. Previous studies have revealed ammonia inhibition on microbial flora by AD performance, but the effect mechanism of ammonia on microbial metabolism remains poorly understood. In this study, we constructed a mesophilic chemostat fed with acetate as the sole carbon source, gradually increased the total ammonia nitrogen (TAN) concentration from 1 g L−1 to 6 g L−1, and employed the 16S rRNA gene, metagenomics, and metatranscriptomics analysis to characterize the microbial community structure and metabolic behavior. The results showed that even at the TAN of 6 g L−1 (pH 7.5), the methanogenesis kept normal, the biogas production was approximately 92% of that at TAN of 1 g L−1 and the acetate degradation ratio reached 99%, suggesting the strong TAN tolerance of the microbial community enriched. 16S rRNA gene analysis suggested that the microbial community structure changed along with the TAN concentration. Methanothrix predominated in methanogens all the time, in which the dominant species was gradually replaced from M. soehngenii to M. harundinacea with the increased TAN. Dominant bacterial species also changed and Proteiniphilum showed a significant positive correlation with increased TAN. Meta-omics analysis showed that the absolute dominant microorganisms at TAN of 6 g L−1 were M. harundinacea and Proteiniphilum, both of which highly expressed genes for anti-oxidative stress. M. harundinacea and the second dominant methanogen Methanosarcina highly expressed both acetate cleavage and CO2 reduction pathways, suggesting the possibility that these two pathways contributed to methanogenesis together. Proteiniphilum and some other species in Firmicutes and Synergistetes were likely acetate oxidizers in the community as they highly expressed genes for syntrophic acetate oxidization, H2 generation, and electron transfer. These results suggested that Proteiniphilum as well as M. harundinacea have strong ammonia tolerance and played critical roles in acetate degradation under ammonia-suppressed conditions. The achievements of the study would contribute to the regulation and management of the AD process.
Thermal EHL analysis of the inner ring rib and roller end in tapered roller bearings with the Carreau model
Authors: Liu Xiaoling , Long Tao , Li Xinming , Guo Feng
Published: January 2023

The roller end/rib contact of tapered roller bearings significantly affects lubricating condition and power loss. To improve the lubrication performance of the inner ring rib and the large end of the roller in tapered roller bearings used in railway coaches, based on the structural analysis of the inner rib and the large end of the roller and considering spin–slide effects between the rib and the large end of the roller, a thermal elastohydrodynamic lubrication model with a Carreau rheological model was established in a tapered roller bearing. Two kinds of rib structures were provided: the tapered rib and spherical rib. Under different conditions, variations in the friction coefficient versus the ratio of curvature radius of the large end of the roller to that of the rib were compared, and the film thickness and film temperature varied with the rotational speed and the effect of load was compared between the two rib structures. Results showed that spinning motion has little effect on the lubrication at the contact point between the inner ring rib and the large end of the tapered roller. There exists an optimal ratio of the curvature radius between the large end of the roller and the spherical or tapered rib; moreover, the friction coefficient corresponding to this optimal ratio value is the smallest. With the increase in the inner ring speed, both film thickness and temperature increase for the two rib structures. Different from the spherical rib, the difference between the minimum and the central film thickness is almost unchangeable, and the tapered rib shows a slight temperature rise. As the load increases, the difference between the minimum and the central film thickness becomes larger, and the temperature in the contact zone gradually increases for the two ribs. Different from the tapered rib, the lower frictional coefficient and lower minimum film thickness are generated for the spherical rib because of higher film temperature.
Mitigating effects and mechanisms of Tai Chi on mild cognitive impairment in the elderly
Authors: Wang Xin , Si Keyi , Gu Wei , Wang Xueqiang
Published: January 2023

Mild cognitive impairment (MCI) is a major public health concern that endangers health and decreases the quality of life of the elderly around the world. A recent clinical guideline has recommended regular exercise (twice per week) for patients with MCI as part of an overall approach to management. Tai Chi, a form of light-to-moderate-intensity mind-body exercise, is particularly suitable for seniors. This review aims to summarize epidemiological studies related to the effects of Tai Chi on symptom remission in older adults with MCI and reveal the potential mechanisms. Evidence suggested that Tai Chi can improve cognitive functions and alleviate the accompanying symptoms of MCI in the elderly potentially by activating the expression of signals in different brain regions, altering their connectivity, increasing the brain volume, and modulating brain-derived neurotropic and inflammation factors. Studies comparing various types of Tai Chi may contribute to the identification of paradigms that have appropriate intensities and difficulty and exert good effects on older people with MCI. In addition, studies are warranted to determine the frequency and duration of training that can optimize the beneficial effects of Tai Chi on MCI.
Age and APOE affect L-carnitine system metabolites in the brain in the APOE-TR model
Authors: Huguenard Claire J. C. , Cseresznye Adam , Darcey Teresa , Nkiliza Aurore , Evans James E. , Hazen Stanley L. , Mullan Michael , Crawford Fiona , Abdullah Laila
Published: January 2023

With age the apolipoprotein E (APOE) E4 allele (involved in lipid homeostasis) is associated with perturbation of bioenergetics pathways in Alzheimer’s disease (AD). We therefore hypothesized that in aging mice APOE genotype would affect the L-carnitine system (central to lipid bioenergetics), in the brain and in the periphery. Using liquid chromatography-mass spectrometry, levels of L-carnitine and associated metabolites: γ-butyrobetaine (GBB), crotonobetaine, as well as acylcarnitines, were evaluated at 10-, 25-, and 50-weeks, in the brain and the periphery, in a targeted replacement mouse model of human APOE (APOE-TR). Aged APOE-TR mice were also orally administered 125 mg/kg of L-carnitine daily for 7 days followed by evaluation of brain, liver, and plasma L-carnitine system metabolites. Compared to E4-TR, an age-dependent increase among E2- and E3-TR mice was detected for medium- and long-chain acylcarnitines (MCA and LCA, respectively) within the cerebrovasculature and brain parenchyma. While following L-carnitine oral challenge, E4-TR mice had higher increases in the L-carnitine metabolites, GBB and crotonobetaine in the brain and a reduction of plasma to brain total acylcarnitine ratios compared to other genotypes. These studies suggest that with aging, the presence of the E4 allele may contribute to alterations in the L-carnitine bioenergetic system and to the generation of L-carnitine metabolites that could have detrimental effects on the vascular system. Collectively the E4 allele and aging may therefore contribute to AD pathogenesis through aging-related lipid bioenergetics as well as cerebrovascular dysfunctions.
The emerging significance of nanomedicine-based approaches to fighting COVID-19 variants of concern: A perspective on the nanotechnology’s role in COVID-19 diagnosis and treatment
Authors: Singh Chandra Kant , Sodhi Kushneet Kaur
Published: January 2023

COVID-19, one of the worst-hit pandemics, has quickly spread like fire across nations with very high mortality rates. Researchers all around the globe are making consistent efforts to address the main challenges faced due to COVID-19 infection including prompt diagnosis and therapeutics to reduce mortality. Conventional medical technology does not effectively contain the havoc caused by deadly COVID-19. This signals a crucial mandate for innovative and novel interventions in diagnostics and therapeutics to combat this ongoing pandemic and counter its successor or disease if it were ever to arise. The expeditious solutions can spring from promising areas such as nanomedicine and nanotechnology. Nanomedicine is a dominant tool that has a huge potential to alleviate the disease burden by providing nanoparticle-based vaccines and carriers. Nanotechnology encompasses multidisciplinary aspects including artificial intelligence, chemistry, biology, material science, physical science, and medicine. Nanoparticles offer many advantages compared to larger particles, including better magnetic properties and a multiplied surface-to-volume ratio. Given this, the present review focuses on promising nanomedicine-based solutions to combat COVID-19 and their utility to control a broad range of pathogens and viruses, along with understanding their role in the therapy, diagnosis, and prevention of COVID-19. Various studies, reports, and recent research and development from the nanotechnology perspective are discussed in this article.
Anterior cingulate cortex, but not amygdala, modulates the anxiogenesis induced by living with conspecifics subjected to chronic restraint stress in male mice
Authors: Silveira Lara Maria , Tavares Ligia Renata Rodrigues , Baptista-de-Souza Daniela , Carmona Isabela Miranda , Carneiro de Oliveira Paulo Eduardo , Nunes-de-Souza Ricardo Luiz , Canto-de-Souza Azair
Published: January 2023

Cohabitation with a partner undergoing chronic restraint stress (CRE) induces anxiogenic-like behaviors through emotional contagion. We hypothesized that the anterior cingulate cortex (ACC) and the amygdala would be involved in the modulation of this emotional process. This study investigated the role of the ACC and amygdala in empathy-like behavior (e.g., anxiety-like responses) induced by living with a mouse subjected to CRE. Male Swiss mice were housed in pairs for 14 days and then allocated into two groups: cagemate stress (one animal of the pair was subjected to 14 days of restraint stress) and cagemate control (no animal experienced stress). Twenty-four hours after the last stress session, cagemates had their brains removed for recording FosB labeling in the ACC and amygdala (Exp.1). In experiments 2 and 3, 24 h after the last stress session, the cagemates received 0.1 μL of saline or cobalt chloride (CoCl2 1 mM) into the ACC or amygdala, and then exposed to the elevated plus-maze (EPM) for recording anxiety. Results showed a decrease of FosB labeling in the ACC without changing immunofluorescence in the amygdala of stress cagemate mice. Cohabitation with mice subjected to CRE provoked anxiogenic-like behaviors. Local inactivation of ACC (but not the amygdala) reversed the anxiogenic-like effects induced by cohabitation with a partner undergoing CRE. These results suggest the involvement of ACC, but not the amygdala, in anxiety induced by emotional contagion.
Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation
Authors: Piekna-Przybylska Dorota , Na Daxiang , Zhang Jingyuan , Baker Cameron , Ashton John M. , White Patricia M.
Published: January 2023

Hearing loss caused by the death of cochlear hair cells (HCs) might be restored through regeneration from supporting cells (SCs) via dedifferentiation and proliferation, as observed in birds. In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. Here we analyze single cell transcriptomes from neonatal mouse cochlear SCs with activated ERBB2, with the goal of identifying potential secreted effectors. ERBB2 induction in vivo generated a new population of cells with de novo expression of a gene network. Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. We validated mRNA expression of network members, and then extended our analysis to older stages. ERBB2 signaling in young adult SCs also promoted protein expression of gene network members. Furthermore, we found proliferating cochlear cell aggregates in the organ of Corti. Our results suggest that ectopic activation of ERBB2 signaling in cochlear SCs can alter the microenvironment, promoting proliferation and cell rearrangements. Together these results suggest a novel mechanism for inducing stem cell-like activity in the adult mammalian cochlea.
The potential of mHealth for older adults on dialysis and their care partners: What’s been done and where do we go from here?
Authors: Burrows Brett , DePasquale Nicole , Ma Jessica , Bowling C. Barrett
Published: January 2023

Self-care, or the dynamic, daily process of becoming actively involved in one’s own care, is paramount to prevent and manage complications of end-stage kidney disease. However, many older dialysis patients face distinctive challenges to adequate engagement in self-care. One promising strategy for facilitating self-care among older dialysis patients and their care partners is the utilization of mobile health (mhealth). mHealth encompasses mobile and wireless communication devices used to improve healthcare delivery, patient and care partner outcomes, and patient care. In other disease populations, mHealth has been linked to maintenance of or improvements in self-management, medication compliance, patient education, and patient-provider communication, all of which can slow disease progression. Although mHealth is considered feasible, acceptable, and clinically useful, this technology has predominately targeted younger patients. Thus, there is a need to develop mHealth for older dialysis patients and their care partners. In this article, we describe current mHealth usage in older dialysis patients, including promising findings, challenges, and research gaps. Given the lack of research on mHealth among care partners of older dialysis patients, we highlight lessons learned from other disease populations to inform the future design and implementation of mHealth for these key stakeholders. We also propose that leveraging care partners represents an opportunity to meaningfully tailor mHealth applications and, by extension, improve care partner physical and mental health and decrease caregiver burden. We conclude with a summary of future directions to help older dialysis patients and their care partners receive recognition as target end-users amid the constant evolution of mHealth.
Vagus nerve stimulation for pharmacoresistant epilepsy secondary to encephalomalacia: A single-center retrospective study
Authors: Guo Mengyi , Wang Jing , Xiong Zhonghua , Deng Jiahui , Zhang Jing , Tang Chongyang , Kong Xiangru , Wang Xiongfei , Guan Yuguang , Zhou Jian , Zhai Feng , Luan Guoming , Li Tianfu
Published: January 2023

Objective

Vagus nerve stimulation (VNS) is an adjunctive treatment for pharmacoresistant epilepsy. Encephalomalacia is one of the most common MRI findings in the preoperative evaluation of patients with pharmacoresistant epilepsy. This is the first study that aimed to determine the effectiveness of VNS for pharmacoresistant epilepsy secondary to encephalomalacia and evaluate the potential predictors of VNS effectiveness.

Methods

We retrospectively analyzed the seizure outcomes of VNS with at least 1 year of follow-up in all patients with pharmacoresistant epilepsy secondary to encephalomalacia. Based on the effectiveness of VNS (≥50% or <50% reduction in seizure frequency), patients were divided into two subgroups: responders and non-responders. Preoperative data were analyzed to screen for potential predictors of VNS effectiveness.

Results

A total of 93 patients with epilepsy secondary to encephalomalacia who underwent VNS therapy were recruited. Responders were found in 64.5% of patients, and 16.1% of patients achieved seizure freedom at the last follow-up. In addition, the responder rate increased over time, with 36.6, 50.5, 64.5, and 65.4% at the 3-, 6-, 12-, and 24-month follow-ups, respectively. After multivariate analysis, seizure onset in adults (>18 years old) (OR: 0.236, 95%CI: 0.059–0.949) was found to be a positive predictor, and the bilateral interictal epileptic discharges (IEDs) (OR: 3.397, 95%CI: 1.148–10.054) and the bilateral encephalomalacia on MRI (OR: 3.193, 95%CI: 1.217–8.381) were found to be negative predictors of VNS effectiveness.

Conclusion

The results demonstrated the effectiveness and safety of VNS therapy in patients with pharmacoresistant epilepsy secondary to encephalomalacia. Patients with seizure onset in adults (>18 years old), unilateral IEDs, or unilateral encephalomalacia on MRI were found to have better seizure outcomes after VNS therapy.
Acupuncture for mild cognitive impairment: A systematic review with meta-analysis and trial sequential analysis
Authors: Yin Zihan , Li Yaqin , Jiang Cheng , Xia Manze , Chen Zhenghong , Zhang Xinyue , Zhao Ling , Liang Fanrong
Published: January 2023

Background

There is insufficient evidence to support the use of acupuncture for mild cognitive impairment (MCI), and there is no consensus on its efficacy. This review aimed to determine the acupuncture effect in patients with MCI.

Methods

Relevant and potentially eligible randomized controlled trials (RCTs) of acupuncture for MCI were obtained from four Chinese databases, four English databases, and additional resources up to 1 August 2022. The primary outcome was the improvement in overall cognitive function (OCF). Secondary outcomes were improved memory function (MF) and activities of daily living (ADLs). The revised Cochrane collaboration risk of bias (ROB) assessment tool (ROB 2.0) was applied to evaluate their methodological quality. The Review Manager software v 5.4 was used for analyses. Trial sequential analysis (TSA) 0.9.5.10 β software was used to estimate the required sample size and test the reliability of the pooled outcome. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool.

Results

This meta-analysis included 11 RCTs with a total of 602 patients. The methodological quality of all trials was moderate. Low-quality evidence showed that acupuncture significantly improved OCF (Mini-Mental State Examination (MMSE): mean difference (MD) = 1.22, 95% confidence interval (CI): 0.78–1.66; the Montreal Cognitive Assessment Scale (MoCA): MD = 1.22, 95% CI: 0.47–1.97). In subgroup analyses, it was revealed that acupuncture significantly increased OCF in patients with MCI when compared to conventional medicine (CM) and sham acupuncture (SA). TSA's findings indicated that the evidence of improving OCF with acupuncture for patients with MCI was conclusive. Meanwhile, there is no statistical difference in the improvement of MF and ADL between acupuncture and CM. TSA showed that the evidence of improving MF and ADL for patients who had MCI and received acupuncture was inconclusive. The shreds of evidence of improving MF and ADL were ranked from low to critically low.

Conclusion

Acupuncture appears to be an effective clinical application method for improving OCF in patients with MCI. However, due to low-quality evidence, more relevant and high-quality research is needed in this field.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021291284, PROSPERO, No. CRD42021291284.
Relationship between gray matter structure and age in children and adolescents with high-functioning autism spectrum disorder
Authors: Sun Fenfen , Chen Yue , Huang Yingwen , Yan Jing , Chen Yihong
Published: January 2023

Objective

The present study used magnetic resonance imaging to investigate the difference in the relationship between gray matter structure and age in children and adolescents with autism spectrum disorder (ASD) and typically developing (TD) subjects.

Methods

After screening T1 structural images from the Autism Brain Imaging Data Exchange (ABIDE) database, 111 children and adolescents (7–18 years old) with high-functioning ASD and 151 TD subjects matched for age, sex and full IQ were included in the current study. By using the voxel-based morphological analysis method, gray matter volume/density (GMV/GMD) maps were obtained for each participant. Then, a multiple regression analysis was performed for ASD and TD groups, respectively to estimate the relationship between GMV/GMD and age with gender, education, site, and IQ scores as covariates. Furthermore, a z-test was used to compare such relationship difference between the groups.

Results

Results showed that compared with TD, the GMD of ASD showed stronger positive correlations with age in the prefrontal cortex, and a stronger negative correlation in the left inferior parietal lobule, and a weaker positive correlation in the right inferior parietal lobule. The GMV of ASD displayed stronger positive correlations with age in the prefrontal cortex and cerebellum.

Conclusion

These findings may provide evidence to support that the brain structure abnormalities underlying ASD during childhood and adolescence may differ from each other.
Perspective: Acknowledging complexity to advance the understanding of developmental coordination disorder
Authors: Meachon Emily J.
Published: January 2023

Developmental Coordination Disorder (DCD) is a heterogeneous neurodevelopmental disorder known for primary symptoms of motor learning and execution difficulties. Recent research has consistently suggested DCD symptoms span broadly beyond motor difficulties, yet a majority of research and practice approaches the investigation, diagnosis, and treatment of DCD with a reductionist framework. Therefore, this paper suggests the paradigm of complexity theory as a means for better conceptualization, assessment, and treatment of DCD. First, the perspective of complexity theory and its relevance to DCD is described. Then, examples from recent research which attempt to acknowledge and capture the complex nature of DCD are highlighted. Finally, suggestions for considering and measuring complexity of DCD in future research and practice are provided. Overall, the perspective of complexity can propel the research forward and improve the understanding of DCD relevant to assessment and treatment. The complexity paradigm is highly relevant to describing the evolving and multidimensional picture of DCD, understanding heterogeneous symptom profiles, making connections to interconnected secondary symptoms, and beyond.
Association of sub-acute changes in plasma amino acid levels with long-term brain pathologies in a rat model of moderate-severe traumatic brain injury
Authors: To Xuan Vinh , Mohamed Abdalla Z. , Cumming Paul , Nasrallah Fatima A.
Published: January 2023

Introduction

Traumatic brain injury (TBI) induces a cascade of cellular alterations that are responsible for evolving secondary brain injuries. Changes in brain structure and function after TBI may occur in concert with dysbiosis and altered amino acid fermentation in the gut. Therefore, we hypothesized that subacute plasma amino acid levels could predict long-term microstructural outcomes as quantified using neurite orientation dispersion and density imaging (NODDI).

Methods

Fourteen 8–10-week-old male rats were randomly assigned either to sham (n = 6) or a single moderate-severe TBI (n = 8) procedure targeting the primary somatosensory cortex. Venous blood samples were collected at days one, three, seven, and 60 post-procedure and NODDI imaging were carried out at day 60. Principal Component Regression analysis was used to identify time dependent plasma amino acid concentrations after in the subacute phase post-injury that predicted NODDI metric outcomes at day 60.

Results

The TBI group had significantly increased plasma levels of glutamine, arginine, alanine, proline, tyrosine, valine, isoleucine, leucine, and phenylalanine at days three-seven post-injury. Higher levels of several neuroprotective amino acids, especially the branched-chain amino acids (valine, isoleucine, leucine) and phenylalanine, as well as serine, arginine, and asparagine at days three-seven post-injury were also associated with lower isotropic diffusion volume fraction measures in the ventricles and thus lesser ventricular dilation at day 60.

Discussion

In the first such study, we examined the relationship between the long-term post-TBI microstructural outcomes across whole brain and the subacute changes in plasma amino acid concentrations. At days three to seven post-injury, we observed that increased plasma levels of several amino acids, particularly the branched-chain amino acids and phenylalanine, were associated with lesser degrees of ventriculomegaly and hydrocephalus TBI neuropathology at day 60 post-injury. The results imply that altered amino acid fermentation in the gut may mediate neuroprotection in the aftermath of TBI.