bluuebunny/crossref_metadata_2025 huggingface dataset:
Autoantibodies elicited with SARS-CoV-2 infection are linked to alterations in double negative B cells
Authors: Castleman Moriah J. , Stumpf Megan M. , Therrien Nicholas R. , Smith Mia J. , Lesteberg Kelsey E. , Palmer Brent E. , Maloney James P. , Janssen William J. , Mould Kara J. , Beckham J. David , Pelanda Roberta , Torres Raul M.
Published: September 2022

Double negative (DN) B cells (CD27-IgD-) comprise a heterogenous population of DN1, DN2, and the recently described DN3 and DN4 subsets. In autoimmune disease, DN2 cells are reported to be precursors to autoreactive antibody secreting cells and expansion of DN2 cells is linked to elevated interferon levels. Severe SARS-CoV-2 infection is characterized by elevated systemic levels of pro-inflammatory cytokines and serum autoantibodies and expansion of the DN2 subset in severe SARS-CoV-2 infection has been reported. However, the activation status, functional capacity and contribution to virally-induced autoantibody production by DN subsets is not established. Here, we validate the finding that severe SARS-CoV-2 infection is associated with a reduction in the frequency of DN1 cells coinciding with an increase in the frequency of DN2 and DN3 cells. We further demonstrate that with severe viral infection DN subsets are at a heightened level of activation, display changes in immunoglobulin class isotype frequency and have functional BCR signaling. Increases in overall systemic inflammation (CRP), as well as specific pro-inflammatory cytokines (TNFα, IL-6, IFNγ, IL-1β), significantly correlate with the skewing of DN1, DN2 and DN3 subsets during severe SARS-CoV-2 infection. Importantly, the reduction in DN1 cell frequency and expansion of the DN3 population during severe infection significantly correlates with increased levels of serum autoantibodies. Thus, systemic inflammation during SARS-CoV-2 infection drives changes in Double Negative subset frequency, likely impacting their contribution to generation of autoreactive antibodies.
Perspectives on the mechanism of pyroptosis after intracerebral hemorrhage
Authors: Song Dengpan , Yeh Chi-Tai , Wang Jian , Guo Fuyou
Published: September 2022

Intracerebral hemorrhage (ICH) is a highly harmful neurological disorder with high rates of mortality, disability, and recurrence. However, effective therapies are not currently available. Secondary immune injury and cell death are the leading causes of brain injury and a poor prognosis. Pyroptosis is a recently discovered form of programmed cell death that differs from apoptosis and necrosis and is mediated by gasdermin proteins. Pyroptosis is caused by multiple pathways that eventually form pores in the cell membrane, facilitating the release of inflammatory substances and causing the cell to rupture and die. Pyroptosis occurs in neurons, glial cells, and endothelial cells after ICH. Furthermore, pyroptosis causes cell death and releases inflammatory factors such as interleukin (IL)-1β and IL-18, leading to a secondary immune-inflammatory response and further brain damage. The NOD-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) pathway plays the most critical role in pyroptosis after ICH. Pyroptosis can be inhibited by directly targeting NLRP3 or its upstream molecules, or directly interfering with caspase-1 expression and GSDMD formation, thus significantly improving the prognosis of ICH. The present review discusses key pathological pathways and regulatory mechanisms of pyroptosis after ICH and suggests possible intervention strategies to mitigate pyroptosis and brain dysfunction after ICH.
Influence of Eimeria maxima coccidia infection on gut microbiome diversity and composition of the jejunum and cecum of indigenous chicken
Authors: Jebessa Endashaw , Guo Lijin , Chen Xiaolan , Bello Semiu Folaniyi , Cai Bolin , Girma Mekonnen , Hanotte Olivier , Nie Qinghua
Published: September 2022

Coccidiosis is an economically significant protozoan disease and an intracellular parasite that significantly impacts poultry production. The gastrointestinal tract microbiota plays a central role in host health and metabolism, and these microbes enhance chickens’ immune systems and nutrient absorption. In this study, we analyzed the abundance and diversity of microbiota of the jejunum and cecum of a dual-purpose indigenous Horro chicken following Eimeria maxima infection. We compared microbial abundance, composition, and diversity at the 4- and 7- days post-infection using 16S rRNA gene sequencing. We obtained, on average, 147,742 and 132,986 high-quality sequences per sample for jejunum and cecum content, respectively. Firmicutes, Proteobacteria, Campilobacterota and Bacteroidota were the major microbial phylum detected in the jejunum content. Firmicutes were the dominant phylum for 4- and 7-days jejunum control groups accounting for (>60% of the sequences). In the infected group Campilobacterota was the dominant phylum in the jejunum (> 24% of sequences) at 4-and 7-days post-infection groups, while Proteobacteria was predominant at 4- and 7-days post-infection of the cecum (> 40% of the sequences). The microbial genus Lactobacillus and Helicobacter were found in the jejunum, while Alistipes, Barnesiella and Faecalibacterium were detected in the cecum. In the jejunum, Helicobacter was dominant at 4 -and-7 days post-infection (≥24%), and Lactobacillus was dominant at 4 -and 7- days in the control group (> 50%). In 4- and 7-days post-infection, Alistipes genus was the more prevalent (> 38%) in the cecum. Thus, clear differences were observed in the bacterial microbiota distribution and abundance between the jejunum and cecum, as well as between infected and control groups for both tissues. The results indicate that chicken intestinal microbial imbalance (dysbiosis) is associated with Eimeria parasite infection and will likely affect the host-microbial non-pathogenic and pathogenic molecular interactions.
Cytopenia after chimeric antigen receptor T cell immunotherapy in relapsed or refractory lymphoma
Authors: Zhou Jin , Zhang Ying , Shan Meng , Zong Xiangping , Geng Hongzhi , Li Jiaqi , Chen Guanghua , Yu Lei , Xu Yang , Li Caixia , Wu Depei
Published: September 2022

Background

Patients with relapsed or refractory (R/R) lymphomas have benefited from chimeric antigen receptor (CAR)-T-cell therapy. However, this treatment is linked to a high frequency of adverse events (AEs), such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and hematologic toxicity. There has been increasing interest in hematological toxicity in recent years, as it can result in additional complications, such as infection or hemorrhage, which remain intractable.

Methods

We conducted a retrospective, single-institution study to evaluate the patterns and outcomes of cytopenia following CAR-T-cell infusion and potential associated factors.

Results

Overall, 133 patients with R/R lymphoma who received CAR-T-cell therapy from June, 2017 to April, 2022 were included in this analysis. Severe neutropenia, anemia and thrombocytopenia occurred frequently (71, 30 and 41%, respectively) after CAR-T-cell infusion. A total of 98% of severe neutropenia and all severe thrombocytopenia cases occurred in the early phase. Early severe cytopenia was associated with CRS incidence and severity, as well as peak inflammatory factor (IL-6, C-reactive protein (CRP), and ferritin) levels. In multivariate analysis, prior hematopoietic stem cell transplantation (HSCT), baseline hemoglobin (HB), and lymphodepleting chemotherapy were independent adverse factors associated with early severe cytopenia. In addition, 18% and 35% of patients had late neutrophil- and platelet (PLT)-related toxicity, respectively. In multivariate analysis, lower baseline PLT count was an independent factor associated with late thrombocytopenia. More severe cytopenia was associated with higher infection rates and poorer survival.

Conclusions

This research indicates that improved selection of patients and management of CRS may help to decrease the severity of cytopenias and associated AEs and improve survival following CAR-T-cell therapy.

Clinical Trial Registration

https://www.clinicaltrials.gov/ct2/show/NCT03196830, identifier NCT03196830.
Common adverse events following immunization with the COVID-19 comirnaty vaccine (Pfizer-BioNTech) among adult population in Hanoi, Vietnam, 2021
Authors: Le Xuan Thi Thanh , Hoang Quan Long , Ta Nhung Thi Kim , Pham Quan Thi , Nguyen Thao Thanh , Phan Huong Thi Mai , Nguyen Thanh Van , Le Ha Thi Thanh , Nguyen Nam Thuy , Hoang Linh Dieu , Luong Phuong Thi Huyen , An Lien Hong , Nguyen Thu Ha , Nguyen Thinh Thi , Nguyen Hien Thuy , Le Huong Thu , Nguyen Doanh Quoc , Nguyen Phuong Viet , Nguyen Tuan Xuan , Do Toan Thi Thanh , Nguyen Thang Huu
Published: September 2022

Rationale

To prevent and control the COVID-19 pandemic, the biggest immunization campaign in history had been deployed worldwide. Therefore, it is important to inform the adverse events following immunization (AEFI) to populations.

Objectives

To prevent vaccine hesitancy, this study focused on finding the common AEFI with the COVID-19 Comirnaty vaccine (Pfizer-BioNTech) among participants aged 18 and above and related factors in Hanoi, Vietnam.

Methods

A cross-sectional study was carried out to collect participants’ data and AEFI after being vaccinated at Hanoi Medical University, Vietnam, in 2021. Logistic regression was utilized for analyzing the correlated factors of AEFI.

Results

We recruited a random sample of 820 participants who received both basic doses of Pfizer vaccine in September and October 2021. The proportion of AEFI after the first dose, second dose, and both doses of Pfizer vaccine was 24.4%, 64.2%, and 18.5%, respectively. AEFI mostly appeared within 1 day and lasted for 1 to 2 days. The AEFI were more common in females (OR=1.7; 95%CI=1.25–2.29) and younger age groups (OR=1.9; 95%CI=1.37–2.58). History of allergy, allergic diseases, chronic diseases, and occupations were not statistically significant with AEFI.

Conclusion

Our findings indicated that the COVID-19 Comirnaty vaccine is safe to be injected. Gender and age group are important factors influencing AEFI.
Coastal upwelling enhances abundance of a symbiotic diazotroph (UCYN-A) and its haptophyte host in the Arctic Ocean
Authors: Selden Corday R. , Einarsson Sveinn V. , Lowry Kate E. , Crider Katherine E. , Pickart Robert S. , Lin Peigen , Ashjian Carin J. , Chappell P. Dreux
Published: September 2022

The apparently obligate symbiosis between the diazotroph Candidatus Atelocyanobacterium thalassa (UCYN-A) and its haptophyte host, Braarudosphaera bigelowii, has recently been found to fix dinitrogen (N2) in polar waters at rates (per cell) comparable to those observed in the tropical/subtropical oligotrophic ocean basins. This study presents the novel observation that this symbiosis increased in abundance during a wind-driven upwelling event along the Alaskan Beaufort shelfbreak. As upwelling relaxed, the relative abundance of B. bigelowii among eukaryotic phytoplankton increased most significantly in waters over the upper slope. As the host’s nitrogen demands are believed to be supplied primarily by UCYN-A, this response suggests that upwelling may enhance N2 fixation as displaced coastal waters are advected offshore, potentially extending the duration of upwelling-induced phytoplankton blooms. Given that such events are projected to increase in intensity and number with ocean warming, upwelling-driven N2 fixation as a feedback on climate merits investigation.
By-catch of sea turtles in Pacific artisanal fishery: Two points of view: From observer and fishers
Authors: Carpio Antonio José , Álvarez Yamel , Serrano Rocio , Vergara M. Belen , Quintero Erklin , Tortosa Francisco S. , Rivas Marga L.
Published: September 2022

Fisheries bycatch is a primary driver of population declines in marine megafauna. These captures not only have environmental impacts, they also have economic consequences for fishers such as direct losses when repairing fishing gear. Therefore, evaluating the fishers’ perception of bycatch and comparing it with data from scientific fisheries observers might provide a broader view of the current situation these species face. To do this, we obtained data concerning the bycatch of 1,838 sea turtles between 2008-2018 in the Eastern Pacific Ocean as well as informative surveys from 421 artisanal fishers surveyed in 2020. There is a discrepancy between the bycatch observed and the fishers’ perceptions of it. The observers’ results identified that high rates of incidental capture of sea turtles are associated with the mahi mahi fishery that occurs during winter and is a shallow set fishery using fish as bait. The olive ridley turtle was the main species affected by bycatch. According to the fishers’ perception, bycatch was higher with the use of J-hooks and a longline (compared to circle hooks and to gill nets and trawl nets) and when the target species are pelagic fish during the winter season. In addition, the fishers’ perception showed that 39.4% considered incidental fishing as an environmental problem and 28.5% considered it as a nuisance, while 32.1% do not consider sea turtle bycatch as a problem. These findings suggest that 60% of fishers do not consider it a need to protect sea turtles. Given the different responses between fisheries observers and fishers’ perception, it is clear that more dialogue is necessary to raise awareness about the effects of bycatch on worldwide sea turtle populations. Thus, there is an enormous potential to recruit/increase fishers’ active participation for turtle protection. In this context, the idea of including the fishers’ perception into any management strategy or conservation measure should be reinforced in order to effectively reduce the bycatch of these iconic species.
Toxoplasma gondii seroprevalence in the endangered Australian sea lion (Neophoca cinerea)
Authors: Lindsay Scott A. , Caraguel Charles G. B. , O’Handley Ryan , Šlapeta Jan , Gray Rachael
Published: September 2022

Toxoplasma gondii is a ubiquitous parasite increasingly detected in marine mammals and suspected to contribute to limited recovery of endangered populations. This study reports on the exposure of the Australian sea lion (Neophoca cinerea) to this protozoon using archived adult and pup sera from three island colonies in South Australia. Modified agglutination testing (MAT) detected a seroprevalence of 30.4% (95% CI 13.2-52.9: n = 23) and high antibody titers (512 to > 2048 IU/ml) in adult females (median age 9.5 y, range 5.5-14.5 y) at Dangerous Reef, a felid-free island. Antibodies weren’t detected in any surveyed pup (97.5% CI 0.0-2.0%, n = 184) at two felid-free islands (Dangerous Reef: n = 21; Olive Island: n = 65), nor at Kangaroo Island (n = 98), which has a high-density feral cat population. Kangaroo Island pups of known age were 7-104 d old, while standard length and bodyweight comparison suggested younger and older pup cohorts at Dangerous Reef and Olive Island, respectively. This study provides the first quantification of disease risk in this endangered species from T. gondii exposure. The absence of detectable pup seroconversion supports the lack of detectable congenital transmission, maternal antibody persistence or early post-natal infection in the sampled cohort yet to commence foraging. An extended serosurvey of N. cinerea colonies is recommended to confirm the hypothesis of predominantly forage-associated exposure to T. gondii in this species. Findings have implications for parasitic disease risk in wildlife inhabiting Australia’s islands and for the feral cat control program on Kangaroo Island.
Compositional stability of sediment microbial communities during a seagrass meadow decline
Authors: Markovski Marsej , Najdek Mirjana , Herndl Gerhard J. , Korlević Marino
Published: September 2022

The presence of seagrass shapes surface sediments and forms a specific environment for diverse and abundant microbial communities. A severe decline ofCymodocea nodosa, a widespread seagrass species in the Mediterranean Sea, has been documented. To characterise and assess the changes in microbial community composition during the decline of aCymodocea nodosameadow, Illumina MiSeq sequencing of the V4 region of the 16S rRNA gene was performed. Samples of surface sediments from two sites, one without any vegetation and one with a decliningCymodocea nodosameadow, were collected at monthly intervals from July 2017 to October 2018. Microbial communities were stratified by sediment depth and differed between the vegetated and the nonvegetated site. Although theCymodocea nodosameadow declined to a point where almost no leaves were present, no clear temporal succession in the community was observed. Taxonomic analysis revealed a dominance of bacterial over archaeal sequences, with most archaeal reads classified asNanoarchaeota,Thermoplasmatota,Crenarchaeota, andAsgardarchaeota. The bacterial community was mainly composed ofDesulfobacterota,Gammaproteobacteria,Bacteroidota,Chloroflexi,Planctomycetota, andCampylobacterota. Our results show that sediment microbial communities are remarkably stable and may resist major disturbances such as seagrass meadow decline.
Wellbeing and national identity in three generations of Czech and Slovak Holocaust survivors
Authors: Preiss Marek , Fňašková Monika , Nečasová Markéta , Heissler Radek , Bob Petr , Prokopová Alice , Šamánková Dita , Sanders Edel , Rektor Ivan
Published: September 2022

Subjective wellbeing (SWB) is an important factor of global adjustment. Intergenerational satisfaction in seriously traumatized people has not been studied so far in homogenous populations of Central and Eastern Europe. This study focuses on the SWB in three generations of survivors living in the Czech Republic and Slovakia after World War II (WWII). The focal groups were Holocaust survivors (ages 71–95,n= 47), Holocaust survivors’ children (ages 30–73,n= 86), and their grandchildren (ages 15–48,n= 88), and they were compared to aged-matched groups without Holocaust history. The first and second generation of Holocaust survivors scored significantly lower than the comparison groups in wellbeing, as measured using the Schwartz Outcome Scale-10 (SOS-10). There was no significant difference in life satisfaction in any of the three generations. Within the focal group, identification as Jewish or as also Jewish was comparable in all three generations of Holocaust survivors (74% in the first, 79% in the second, and 66% in the third generation). Holocaust survivors declaring Jewish identity reported lower SWB compared to survivors declaring other than Jewish identity. The focal group generated more national identities than comparisons. The outcomes are discussed in the context of the history of Central and Eastern Europe.
Cellular changes at the glia-neuro-vascular interface in definite idiopathic normal pressure hydrocephalus
Authors: Eide Per Kristian
Published: September 2022

Idiopathic normal pressure hydrocephalus (iNPH) is a subtype of dementia with overlap toward Alzheimer's disease. Both diseases show deposition of the toxic metabolites amyloid-β and tau in brain. A unique feature with iNPH is that a subset of patients may improve clinically following cerebrospinal fluid (CSF) diversion (shunt) surgery. The patients responding clinically to shunting are denoted Definite iNPH, otherwise iNPH is diagnosed as Possible iNPH or Probable iNPH, high-lightening that the clinical phenotype and underlying pathophysiology remain debated. Given the role of CSF disturbance in iNPH, the water channel aquaporin-4 (AQP4) has been suggested a crucial role in iNPH. Altered expression of AQP4 at the astrocytic endfeet facing the capillaries could affect glymphatic function, i.e., the perivascular transport of fluids and solutes, including soluble amyloid-β and tau. This present study asked how altered perivascular expression of AQP4 in subjects with definite iNPH is accompanied with cellular changes at the glia-neuro-vascular interface. For this purpose, information was retrieved from a database established by the author, including prospectively collected management data, physiological data and information from brain biopsy specimens examined with light and electron microscopy. Individuals with definite iNPH were included together with control subjects who matched the definite iNPH cohort closest in gender and age. Patients with definite iNPH presented with abnormally elevated pulsatile intracranial pressure measured overnight. Cortical brain biopsies showed reduced expression of AQP4 at astrocytic endfeet both perivascular and toward neuropil. This was accompanied with reduced expression of the anchor molecule dystrophin (Dp71) at astrocytic perivascular endfeet, evidence of altered cellular metabolic activity in astrocytic endfoot processes (reduced number of normal and increased number of pathological mitochondria), and evidence of reactive changes in astrocytes (astrogliosis). Moreover, the definite iNPH subjects demonstrated in cerebral cortex changes in capillaries (reduced thickness of the basement membrane between astrocytic endfeet and endothelial cells and pericytes, and evidence of impaired blood-brain-barrier integrity). Abnormal changes in neurons were indicated by reduced post-synaptic density length, and reduced number of normal mitochondria in pre-synaptic terminals. In summary, definite iNPH is characterized by profound cellular changes at the glia-neurovascular interface, which probably reflect the underlying pathophysiology.
Effectiveness of therapeutic massage for improving motor symptoms in Parkinson's disease: A systematic review and meta-analysis
Authors: Kang Zhiran , Xing Hua , Lin Qiang , Meng Fanchao , Gong Li
Published: September 2022

Background

Parkinson's disease (PD) causes movement disorders [called motor symptoms (MS)], and motor dysfunction poses a great barrier to the quality of life. Although pharmacological therapy like levodopa can relieve the symptoms, it can also cause complications, such as psychosis, nausea, and dyskinesia. A therapy with more minor side effects is needed for PD. Therapeutic massages are the most commonly used forms of complementary and alternative medicine (CAM), but no systematic review and meta-analysis have focused on the efficacy of massage on PD.

Objective

To evaluate the quality of evidence and efficacy of therapeutic massage for improving MS in PD.

Methods

We independently searched four electronic databases, including Chinese National Knowledge Infrastructure (CNKI), MEDLINE/PubMed, Embase, and Cochrane Library, for randomized controlled trials (RCTs) about therapeutic massage and other available manual therapies improving MS in PD from January 1, 2012, to December 31, 2021 (recent 10 years). The main outcome measures were total effectiveness and the Unified Parkinson's Disease Rating Scale (UPDRS), including UPDRS total, II, and III. For the statistical analysis, the risk ratio, standard mean difference, and 95% confidence interval (CI) were used to calculate effect sizes between groups. To determine heterogeneity, statistical index I2 was used.

Results

A total of 363 PD participants in seven RCTs and one randomized pilot-control study were included in this meta-analysis. The total effectiveness showed that therapeutic massage was more effective than the intervention of the control group for improving MS [ratio risk (RR): 1.33, 95% CI (1.14–1.55), p = 0.0002]. The UPDRS-III scores showed that massage improves motor function more than the control group [SMD = −0.46, 95% CI (−0.67, −0.24), p < 0.00001]. But we found that massage performed no better than the control group in improving daily life activities [SMD = −0.15, 95% CI (−0.40, 0.10), p = 0.23].

Conclusion

Therapeutic massage was effective in improving MS in PD. It is suggested to be an appropriate form of CAM in treating PD.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=323182, identifier: CRD42022323182.
The effect of metformin on ameliorating neurological function deficits and tissue damage in rats following spinal cord injury: A systematic review and network meta-analysis
Authors: Zhou Long-yun , Chen Xu-qing , Yu Bin-bin , Pan Meng-xiao , Fang Lu , Li Jian , Cui Xue-jun , Yao Min , Lu Xiao
Published: September 2022

Spinal cord injury (SCI) is a devastating condition with few treatment options. Metformin, a classical antidiabetic and antioxidant, has extended its application to experimental SCI treatment. Here, we performed a systematic review to evaluate the neurobiological roles of metformin for treating SCI in rats, and to assess the potential for clinical translation. PubMed, Embase, China National Knowledge Infrastructure, WanFang data, SinoMed, and Vip Journal Integration Platform databases were searched from their inception dates to October 2021. Two reviewers independently selected controlled studies evaluating the neurobiological roles of metformin in rats following SCI, extracted data, and assessed the quality of methodology and evidence. Pairwise meta-analyses, subgroup analyses and network analysis were performed to assess the roles of metformin in neurological function and tissue damage in SCI rats. Twelve articles were included in this systematic review. Most of them were of moderate-to-high methodological quality, while the quality of evidence from those studies was not high. Generally, Basso, Beattie, and Bresnahan scores were increased in rats treated with metformin compared with controls, and the weighted mean differences (WMDs) between metformin and control groups exhibited a gradual upward trend from the 3rd (nine studies, n = 164, WMD = 0.42, 95% CI = −0.01 to 0.85, P = 0.06) to the 28th day after treatment (nine studies, n = 136, WMD = 3.48, 95% CI = 2.04 to 4.92, P < 0.00001). Metformin intervention was associated with improved inclined plane scores, tissue preservation ratio and number of anterior horn motor neurons. Subgroup analyses indicated an association between neuroprotection and metformin dose. Network meta-analysis showed that 50 mg/kg metformin exhibited greater protection than 10 and 100 mg/kg metformin. The action mechanisms behind metformin were associated with activating adenosine monophosphate-activated protein kinase signaling, regulating mitochondrial function and relieving endoplasmic reticulum stress. Collectively, this review indicates that metformin has a protective effect on SCI with satisfactory safety and we demonstrate a rational mechanism of action; therefore, metformin is a promising candidate for future clinical trials. However, given the limitations of animal experimental methodological and evidence quality, the findings of this pre-clinical review should be interpreted with caution.
Radically reframing studies on neurobiology and socioeconomic circumstances: A call for social justice-oriented neuroscience
Authors: Webb E. Kate , Cardenas-Iniguez Carlos , Douglas Robyn
Published: September 2022

Socioeconomic circumstances are associated with symptoms and diagnostic status of nearly all mental health conditions. Given these robust relationships, neuroscientists have attempted to elucidate how socioeconomic-based adversity “gets under the skin.” Historically, this work emphasized individual proxies of socioeconomic position (e.g., income, education), ignoring the effects of broader socioeconomic contexts (e.g., neighborhood socioeconomic disadvantage) which may uniquely contribute to chronic stress. This omission represented a disconnect between neuroscience and other allied fields that have recognized health is undeniably linked to interactions between systems of power and individual characteristics. More recently, neuroscience work has considered how sociopolitical context affects brain structure and function; however, the products of this exciting line of research have lacked critical sociological and historical perspectives. While empirical evidence on this topic is burgeoning, the cultural, ethical, societal, and legal implications of this work have been elusive. Although the mechanisms by which socioeconomic circumstances impact brain structure and function may be similar across people, not everyone is exposed to these factors at similar rates. Individuals from ethnoracially minoritized groups are disproportionally exposed to neighborhood disadvantage. Thus, socioeconomic inequities examined in neuroscience research are undergirding with other forms of oppression, namely structural racism. We utilize a holistic, interdisciplinary approach to interpret findings from neuroscience research and interweave relevant theories from the fields of public health, social sciences, and Black feminist thought. In this perspective piece, we discuss the complex relationship that continues to exist between academic institutions and underserved surrounding communities, acknowledging the areas in which neuroscience research has historically harmed and/or excluded structurally disadvantaged communities. We conclude by envisioning how this work can be used; not just to inform policymakers, but also to engage and partner with communities and shape the future direction of human neuroscience research.
Altered levels of variant cholinesterase transcripts contribute to the imbalanced cholinergic signaling in Alzheimer’s and Parkinson’s disease
Authors: Gok Muslum , Madrer Nimrod , Zorbaz Tamara , Bennett Estelle R. , Greenberg David , Bennett David A. , Soreq Hermona
Published: September 2022

Acetylcholinesterase and butyrylcholinesterase (AChE and BChE) are involved in modulating cholinergic signaling, but their roles in Alzheimer’s and Parkinson’s diseases (AD and PD) remain unclear. We identified a higher frequency of the functionally impaired BCHE-K variant (rs1803274) in AD and PD compared to controls and lower than in the GTEx dataset of healthy individuals (n= 651); in comparison, the prevalence of the 5′-UTR (rs1126680) and intron 2 (rs55781031) single-nucleotide polymorphisms (SNPs) of BCHE and ACHE’s 3′-UTR (rs17228616) which disrupt AChE mRNA targeting by miR-608 remained unchanged. qPCR validations confirmed lower levels of the dominant splice variant encoding the “synaptic” membrane-bound ACHE-S in human post-mortem superior temporal gyrus samples from AD and in substantia nigra (but not amygdala) samples from PD patients (n= 79,n= 67) compared to controls, potentially reflecting region-specific loss of cholinergic neurons. In contradistinction, the non-dominant “readthrough” AChE-R mRNA variant encoding for soluble AChE was elevated (p< 0.05) in the AD superior temporal gyrus and the PD amygdala, but not in the neuron-deprived substantia nigra. Elevated levels of BChE (p< 0.001) were seen in AD superior temporal gyrus. Finally, all three ACHE splice variants, AChE-S, AChE-R, and N-extended AChE, were elevated in cholinergic-differentiated human neuroblastoma cells, with exposure to the oxidative stress agent paraquat strongly downregulating AChE-S and BChE, inverse to their upregulation under exposure to the antioxidant simvastatin. The multi-leveled changes in cholinesterase balance highlight the role of post-transcriptional regulation in neurodegeneration. (235)
The role of metabolites under the influence of genes and lifestyles in bone density changes
Authors: Lv Xuewei , Jiang Yanfeng , Yang Dantong , Zhu Chengkai , Yuan Huangbo , Yuan Ziyu , Suo Chen , Chen Xingdong , Xu Kelin
Published: September 2022

Purpose

Osteoporosis is a complex bone disease influenced by numerous factors. Previous studies have found that some metabolites are related to bone mineral density (BMD). However, the associations between metabolites and BMD under the influence of genes and lifestyle have not been fully investigated.

Methods

We analyzed the effect of metabolites on BMD under the synergistic effect of genes and lifestyle, using the data of 797 participants aged 55–65 years from the Taizhou Imaging Study. The cumulative sum method was used to calculate the polygenic risk score of SNPs, and the healthful plant-based diet index was used to summarize food intake. The effect of metabolites on BMD changes under the influence of genes and lifestyle was analyzed through interaction analysis and mediation analysis.

Results

Nineteen metabolites were found significantly different in the osteoporosis, osteopenia, and normal BMD groups. We found two high-density lipoprotein (HDL) subfractions were positively associated with osteopenia, and six very-low-density lipoprotein subfractions were negatively associated with osteopenia or osteoporosis, after adjusting for lifestyles and genetic factors. Tea drinking habits, alcohol consumption, smoking, and polygenic risk score changed BMD by affecting metabolites.

Conclusion

With the increased level of HDL subfractions, the risk of bone loss in the population will increase; the risk of bone loss decreases with the increased level of very-low-density lipoprotein subfractions. Genetic factors and lifestyles can modify the effects of metabolites on BMD. Our results show evidence for the precise prevention of osteoporosis.
Water-soluble tomato concentrate modulates shear-induced platelet aggregation and blood flow in vitro and in vivo
Authors: Liu Lu , Xiao Shunli , Wang Yilin , Wang Yufang , Liu Lei , Sun Zhengxiao , Zhang Qian , Yin Xiaojie , Liao Fulong , You Yun , Zhang Xuguang
Published: September 2022

Water-soluble tomato concentrate (WSTC), extracted from mature tomatoes, is the first health product in Europe that has been approved “to help maintain normal platelet activity to maintain healthy blood flow.” We hypothesized that WSTC might exert an influence on blood flow shear stress-induced platelet aggregation (SIPA) and in turn maintains healthy blood flow. We used a microfluidic system to measure the effects of WSTC on SIPA in vitro. We also used the strenuous exercise rat model and the κ-carrageenan-induced rat tail thrombosis model to demonstrate the effects of WSTC on blood flow. WSTC significantly inhibited platelet aggregation at pathological high shear rate of 4,000 s–1 and 8,000 s–1in vitro (P < 0.05 or P < 0.01). WSTC reduced the platelet adhesion rate and increased the rolling speed of platelets by inhibiting binding to Von Willebrand Factor (vWF) (P < 0.05 or P < 0.01). The oral administration of WSTC for 4 weeks in strenuous exercise rats alleviated hyper-reactivity of the platelets and led to a significant reduction in the plasma levels of catecholamine and IL-6. WSTC treatment also led to a reduction in black tail length, reduced blood flow pulse index (PI) and vascular resistance index (RI), and ameliorated local microcirculation perfusion in a rat model of thrombosis. WSTC exerted obvious inhibitory effects on the platelet aggregation induced by shear flow and alleviated the blood flow and microcirculation abnormities induced by an inflammatory reaction.
Association of hypercalciuria with vitamin D supplementation in patients undergoing ketogenic dietary therapy
Authors: Lee Myeongseob , Lee Hae In , Song Kyungchul , Choi Han Saem , Suh Junghwan , Kim Se Hee , Chae Hyun Wook , Kang Hoon-Chul , Lee Joon Soo , Kim Heung Dong , Kim Ho-Seong , Kwon Ahreum
Published: September 2022

Background

Ketogenic dietary therapy (KDT) is used as an effective treatment for epilepsy. However, KDT carries the risk of bone health deterioration; therefore, vitamin D supplementation is required. Vitamin D replacement therapy in KDT has not been established because it may be related to hypercalciuria/urolithiasis, which are common adverse effects of KDT. Hence, this study aimed to evaluate the dose-dependent association between vitamin D3 and hypercalciuria/urolithiasis in patients undergoing KDT and dose optimization for renal complications.

Materials and methods

Overall, 140 patients with intractable childhood epilepsy started 3:1 KDT (lipid to non-lipid ratio) at the Severance Children’s Hospital from January 2016 to December 2019. Regular visits were recommended after KDT initiation. Participants were assessed for height, weight, serum 25-hydroxyvitamin D (25-OH-D3) level, parathyroid hormone level, and ratio of urinary excretion of calcium and creatinine (Uca/Ucr). Kidney sonography was conducted annually. Patients who already had urolithiasis and were taking hydrochlorothiazide before KDT, failed to maintain KDT for 3 months, did not visit the pediatric endocrine department regularly, did not take prescribed calcium and vitamin D3 properly, or needed hospitalization for > 1°month because of serious medical illness were excluded. Data from patients who started diuretic agents, e.g., hydrochlorothiazide, were excluded from that point because the excretion of calcium in the urine may be altered in these patients.

Result

In total, 49 patients were included in this study. Uca/Ucr ratio significantly decreased with increasing levels of 25-OH-D3 (p = 0.027). The odds ratio for hypercalciuria was 0.945 (95% confidence interval, 0.912–0.979; p = 0.002) per 1.0 ng/mL increment in 25-OH-D3 level. Based on findings of receiver operating characteristic curve analysis and Youden’s J statistic, the cut-off 25-OH-D3 level for preventing hypercalciuria was > 39.1 ng/mL at 6 months. Furthermore, the vitamin D3 supplementation dose cut-off was > 49.5 IU/kg for hypercalciuria prevention.

Conclusion

An inverse relationship between Uca/Ucr ratio and 25-OH-D3 level was noted, which means that vitamin D supplementation is helpful for preventing hypercalciuria related to KDT. We suggest that the recommended 25-OH-D3 level is > 40 ng/mL for hypercalciuria prevention and that KDT for children with epilepsy can be optimized by vitamin D3 supplementation at 50 IU/kg.
Cost-effectiveness of palbociclib in early breast cancer patients with a high risk of relapse: Results from the PENELOPE-B trial
Authors: Galactionova Katya , Loibl Sibylle , Salari Paola , Marmé Frederik , Martin Miguel , Untch Michael , Bonnefoi Hervé R. , Kim Sung-Bae , Bear Harry D. , McCarthy Nicole , Gelmon Karen A. , García-Sáenz José A. , Kelly Catherine M. , Reimer Toralf , Toi Masakazu , Rugo Hope S. , Gnant Michael , Makris Andreas , Burchardi Nicole , Schwenkglenks Matthias
Published: September 2022

Background

Patients with hormone receptor-positive, HER2-negative breast cancer who have residual invasive disease after neoadjuvant chemotherapy (NACT) are at a high risk of relapse. PENELOPE-B was a double-blind, placebo-controlled, phase III trial that investigated adding palbociclib (PAL) for thirteen 28-day cycles to adjuvant endocrine therapy (ET) in these patients. Clinical results showed no significant improvement in invasive disease-free survival with PAL.

Methods

We performed a pre-planned cost-effectiveness analysis of PAL within PENELOPE-B from the perspective of the German statutory health insurance. Health-related quality of life scores, collected in the trial using the EQ-5D-3L instrument, were converted to utilities based on the German valuation algorithm. Resource use was valued using German price weights. Outcomes were discounted at 3% and modeled with mixed-level linear models to adjust for attrition, repeated measurements, and residual baseline imbalances. Subgroup analyses were performed for key prognostic risk factors. Scenario analyses addressed data limitations and evaluated the robustness of the estimated cost-effectiveness of PAL to methodological choices.

Results

The effects of PAL on quality-adjusted life years (QALYs) were marginal during the active treatment phase, increasing thereafter to 0.088 (95% confidence interval: −0.001; 0.177) QALYs gained over the 4 years of follow-up. The incremental costs were dominated by PAL averaging EUR 33,000 per patient; costs were higher in the PAL arm but not significantly different after the second year. At an incremental cost-effectiveness ratio of EUR 380,000 per QALY gained, PAL was not cost-effective compared to the standard-of-care ET. Analyses restricted to Germany and other subgroups were consistent with the main results. Findings were robust in the scenarios evaluated.

Conclusions

One year of PAL added to ET is not cost-effective in women with residual invasive disease after NACT in Germany.
Quantitative high-throughput analysis of tumor infiltrating lymphocytes in breast cancer
Authors: Hayashi Kumiko , Nogawa Daichi , Kobayashi Maki , Asakawa Ayaka , Ohata Yae , Kitagawa Shota , Kubota Kazuishi , Takahashi Hisashi , Yamada Miyuki , Oda Goshi , Nakagawa Tsuyoshi , Uetake Hiroyuki , Onishi Iichiroh , Kinowaki Yuko , Kurata Morito , Kitagawa Masanobu , Yamamoto Kouhei
Published: September 2022

In breast cancer (BC), the development of cancer immunotherapy including immune checkpoint inhibitors has progressed. Tumor infiltrating lymphocytes (TILs) is one of the important factors for an immune response between tumor cells and immune cells in the tumor microenvironment, and the presence of TILs has been identified as predictors of response to chemotherapy. However, because complex mechanisms underlies the crosstalk between immune cells and cancer cells, the relationship between immune profiles in the tumor microenvironment and the efficacy of the immune checkpoint blocked has been unclear. Moreover, in many cases of breast cancer, the quantitative analysis of TILs and immuno-modification markers in a single tissue section are not studied. Therefore, we quantified detailed subsets of tumor infiltrating lymphocytes (TILs) from BC tissues and compared among BC subtypes. The TILs of BC tissues from 86 patients were classified using multiplex immunohistochemistry and an artificial intelligence-based analysis system based on T-cell subset markers, immunomodification markers, and the localization of TILs. The levels of CD4/PD1 and CD8/PD1 double-positive stromal TILs were significantly lower in the HER2- BC subtype (p <0.01 and p <0.05, respectively). In triple-negative breast cancer (TNBC), single marker-positive intratumoral TILs did not affect prognosis, however CD4/PDL1, CD8/PD1, and CD8/PDL1 double-positive TILs were significantly associated with TNBC recurrence (p<0.05, p<0.01, and p<0.001, respectively). TIL profiles differed among different BC subtypes, suggesting that the localization of TILs and their tumor-specific subsets influence the BC microenvironment.
Cancer knowledge and health-consciousness in childhood cancer survivors following transition into adult care—results from the ACCS project
Authors: Otth Maria , Denzler Sibylle , Diesch-Furlanetto Tamara , Scheinemann Katrin
Published: September 2022

Background

Knowledge on chronic medical conditions in childhood cancer survivors (CCSs) is constantly growing and underlines that long-term follow-up (LTFU) care is often mandatory, also in adulthood. However, many CCSs discontinue follow-up care after transition to adult care. One reason might be that the current transition practices do not meet the needs of adolescent and young adult CCSs. We therefore aim to evaluate different transition models for Swiss CCSs by assessing their cancer knowledge, cancer worries, self-management skills, and expectations for LTFU care, following transition in two different hospital-based models.

Methods

Within the Aftercare of Childhood Cancer Survivors (ACCS) study, we performed a questionnaire-based survey with a cross-sectional and longitudinal part. We included 5-year CCSs aged >16 years at recruitment who were transitioned to adult care in two hospitals between 2014 and 2021. Here, we report the results of the cross-sectional part. We compared the survivors’ cancer knowledge with medical record data and assessed cancer worries (6 questions), self-management skills (15 questions), and expectations (12 questions) by validated scales. We used descriptive statistics, chi-squared test, and t-tests to describe the results.

Results

We analyzed 57 CCSs (response rate 44%), 60% of those were female, had a median age of 9 years at diagnosis and 23 years at the questionnaire. Most CCSs recalled their diagnosis (95%) and exposure to treatment modalities (98%) correctly. CCSs worried the most about potential late effects (47%) and issues with having children in the future (44%). At least 75% of CCSs agreed to 12 of the 15 self-management questions, indicating high self-management skills. The top three expectations included that physicians know the survivors’ cancer history, that visits start on time, and that physicians can always be called in case of questions.

Conclusion

CCSs receiving hospital-based LTFU care have good cancer knowledge and high self-management skills. The identified worries and expectations will help to improve the LTFU care of CCSs who transition to adult care, to further inform and educate survivors and healthcare professionals about and might be relevant for other countries with a similar healthcare system.
Prognostic value of combined inflammatory and nutritional biomarkers in HCC within the Milan criteria after hepatectomy
Authors: Feng Hanxin , Xu Feng , Zhao Yang , Jin Tianqiang , Liu Jianbo , Li Rui , Zhou Tianyi , Dai Chaoliu
Published: September 2022

Aims

This study aimed to evaluate the predictive value of the combined prognostic nutritional index (PNI) and GGT/ALT for the postoperative prognosis of patients with hepatocellular carcinoma (HCC) within Milan criteria undergoing radical hepatectomy.

Methods

This single-center retrospective study included 283 patients with HCC within the Milan criteria who underwent hepatectomy. The receiver operating characteristic (ROC) curve was used to calculate the optimal PNI and GGT/ALT cut-off values. Pre-treatment PNI, GGT/ALT, and PNI-GGT/ALT grades were calculated. Overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan–Meier method, and multivariate analysis was used to identify prognostic factors.

Results

Multivariate Cox regression analysis identified that the PNI, GGT/ALT, tumor number were significant prognostic markers for OS, and that the GGT/ALT, tumor number were significant prognostic markers for OS. The survival curves showed that low PNI, high GGT/ALT ratio, and high PNI-GGT/ALT grade were associated with poorer OS and DFS. With an area under the curve (AUC) of 0.690, PNI-GGT/ALT outperformed each individual score.

Conclusion

PNI-GGT/ALT, a new prognostic scoring model, qualifies as a novel prognostic predictor for patients with HCC within the Milan criteria after curative resection.
Four methylation-driven genes detected by linear discriminant analysis model from early-stage colorectal cancer and their methylation levels in cell-free DNA
Authors: Zhan Lei , Sun Changjian , Zhang Yu , Zhang Yue , Jia Yuzhe , Wang Xiaoyan , Li Feifei , Li Donglin , Wang Shen , Yu Tao , Zhang Jingdong , Li Deyang
Published: September 2022

The process of colorectal cancer (CRC) formation is considered a typical model of multistage carcinogenesis in which aberrant DNA methylation plays an important role. In this study, 752 methylation-driven genes (MDGs) were identified by the MethylMix package based on methylation and gene expression data of CRC in The Cancer Genome Atlas (TCGA). Iterative recursive feature elimination (iRFE) based on linear discriminant analysis (LDA) was used to determine the minimum MDGs (iRFE MDGs), which could distinguish between cancer and cancer-adjacent tissues. Further analysis indicated that the changes in methylation levels of the four iRFE MDGs, ADHFE1-Cluster1, CNRIP1-Cluster1, MAFB, and TNS4, occurred in adenoma tissues, while changes did not occur until stage IV in cell-free DNA. Furthermore, the methylation levels of iRFE MDGs were correlated with the genes involved in the reprogramming process of somatic cells to pluripotent stem cells, which is considered the common signature of cancer cells and embryonic stem cells. The above results indicated that the four iRFE MDGs may play roles in the early stage of colorectal carcinogenesis and highlighted the complicated relationship between tissue DNA and cell-free DNA (cfDNA).