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Variation of multifocal electroretinogram (mfERG) data presentation in existing scientific publications is a challenge for eye care practitioners to apply the scientific information for evidence-based practice in patient management. This review offers an overview of the mfERG data presentation types. Eight types of data presentation in the form of a table, scatter plot, line graph, bar graph/box plot, single waveform/a group of waveforms, trace array topography, three-dimensional topography, and two-dimensional topography are identified. The table format is used to provide the exact values. Line graphs, scatter, and box plots offer information about the relationship of mfERG values. Waveforms are helpful for comparison between groups or conditions. Topographies outline the retinal, especially the specific localized retinal abnormalities. An infographic of fundamental mfERG electrical response with definitions and clinical indications is provided to bridge the gap between researchers and clinicians to facilitate efficient clinical application.

IntroductionSolid cancers Myeloid cells are prevalent in solid cancers, but they frequently exhibit an anti-inflammatory pro-tumor phenotype that contribute to the immunosuppressive tumor microenvironment (TME), which hinders the effectiveness of cancer immunotherapies. Myeloid cells’ natural ability of tumor trafficking makes engineered myeloid cell therapy an intriguing approach to tackle the challenges posed by solid cancers, including tumor infiltration, tumor cell heterogenicity and the immunosuppressive TME. One such engineering approach is to target the checkpoint molecule PD-L1, which is often upregulated by solid cancers to evade immune responses.MethodHere we devised an adoptive cell therapy strategy based on myeloid cells expressing a Chimeric Antigen Receptor (CAR)-like immune receptor (CARIR). The extracellular domain of CARIR is derived from the natural inhibitory receptor PD-1, while the intracellular domain(s) are derived from CD40 and/or CD3ζ. To assess the efficacy of CARIR-engineered myeloid cells, we conducted proof-of-principle experiments using co-culture and flow cytometry-based phagocytosis assays in vitro. Additionally, we employed a fully immune-competent syngeneic tumor mouse model to evaluate the strategy’s effectiveness in vivo.ResultCo-culturing CARIR-expressing human monocytic THP-1 cells with PD-L1 expressing target cells lead to upregulation of the costimulatory molecule CD86 along with expression of proinflammatory cytokines TNF-1α and IL-1β. Moreover, CARIR expression significantly enhanced phagocytosis of multiple PD-L1 expressing cancer cell lines in vitro. Similar outcomes were observed with CARIR-expressing human primary macrophages. In experiments conducted in syngeneic BALB/c mice bearing 4T1 mammary tumors, infusing murine myeloid cells that express a murine version of CARIR significantly slowed tumor growth and prolonged survival.ConclusionTaken together, these results demonstrate that adoptive transfer of PD-1 CARIR-engineered myeloid cells represents a promising strategy for treating PD-L1 positive solid cancers.

Abstract Cisplatin-based combination chemotherapy is the foundation for treatment of advanced bladder cancer (BlCa), but many patients develop chemoresistance mediated by increased Akt and ERK phosphorylation. However, the mechanism by which cisplatin induces this increase has not been elucidated. Among six patient-derived xenograft (PDX) models of BlCa, we observed that the cisplatin-resistant BL0269 express high epidermal growth factor receptor, ErbB2/HER2 and ErbB3/HER3. Cisplatin treatment transiently increased phospho-ErbB3 (Y1328), phospho-ERK (T202/Y204) and phospho-Akt (S473), and analysis of radical cystectomy tissues from patients with BlCa showed correlation between ErbB3 and ERK phosphorylation, likely due to the activation of ERK via the ErbB3 pathway. In vitro analysis revealed a role for the ErbB3 ligand heregulin1-β1 (HRG1/NRG1), which is higher in chemoresistant lines compared to cisplatin-sensitive cells. Additionally, cisplatin treatment, both in PDX and cell models, increased HRG1 levels. The monoclonal antibody seribantumab, that obstructs ErbB3 ligand-binding, suppressed HRG1-induced ErbB3, Akt and ERK phosphorylation. Seribantumab also prevented tumor growth in both the chemosensitive BL0440 and chemoresistant BL0269 models. Our data demonstrate that cisplatin-associated increases in Akt and ERK phosphorylation is mediated by an elevation in HRG1, suggesting that inhibition of ErbB3 phosphorylation may be a useful therapeutic strategy in BlCa with high phospho-ErbB3 and HRG1 levels.

Carbon-based electrode as an economically benign choice is widely used in electrochemical or bio-electrochemical systems. However, its poor electrical conductivity that leading high overpotential and energy loss, especially in large scale facilities, remains a bottleneck for its application. Herein, a unique cross-stacking multi-layered reduced graphene oxide (rGO) and polyaniline (PANI) modified carbon brush is fabricated via one-step electro-depositing. In particular, the top-most layer of the modified electrode is orientated controlled to be rGO or PANI layer by adjusting the initial CV scanning in the positive or negative direction. As was indicated by cyclic voltammetry, the improved electrochemical activity is achieved by coupling the advantages of the highly conductive network offered by graphene with desirable stability provided by the well-dispersed deposition of nanoscale PANI particles. In comparison, the modified electrode with rGO on the top-most layer (LrGO) showed higher degree of sp2-hybridized -C-C- ordered structure in Raman profile, lower O/C ratio in XPS analysis, higher Zeta potential (−2.05 mV) and more hydrophilic than unmodified one. Moreover, benefiting from the unique cross-stacking multi-layered matrix of rGO and PANI, the best electrochemical performance was achieved on the electrode LrGO with high exerted electrochemical active surface area (ECSA) of 0.85 mF cm−2, and the charge transfer resistance as low as 0.32 Ω. The findings of this study provide a guidance for the modification and application of carbon-based electrode using rGO and PANI, which potentially enables the scaling-up of carbon-based electrode in various (bio-) electrochemical systems with high electrochemical performance.

IntroductionWith an incidence rate as high as 46%-58%, hypoglycemia is a common complication of glycemic management among those suffering from type 2 diabetes mellitus(T2DM). According to preclinical research, hypoglycemia episodes may impair cognition by harming neurons. However, there is still controversy regarding the clinical evidence for the relationship between hypoglycemic events and the likelihood of cognitive impairment. Furthermore, little research has been done on the dose-response association between hypoglycemia incidents and the possibility of cognitive impairment. To address these knowledge gaps, the present research intends to update the comprehension of the association among hypoglycemic events and the risk of cognitive impairment and to clarify the correlation between dose and response by incorporating the most recent investigations.Method and analysisThis work has developed a protocol for a systematic review and meta-analysis that will examine, via a well-organized assessment of several databases, the relationship between the incidence of hypoglycemia and the probability of cognitive impairment. Observational studies investigating the connection between hypoglycemia episodes and cognitive impairment will be included. The databases that will be searched are PubMed, Web of Science, the Chinese Biomedical Literature Database (CBM), Cochrane Library, Embase, the China National Knowledge (CNKI), Wan Fang, the Chinese Science and Technology Periodical Database (VIP), and Du Xiu. Literature from the establishment of each database to December 2023 will be included in the search. Two researchers will independently screen the studies that satisfy the requirements for both inclusion and exclusion. A third researcher will be asked to mediate any disputes. The methodological caliber of the studies included will be assessed utilizing the Newcastle-Ottawa Scale (NOS) or the Joanna Briggs Institute (JBI) critical appraisal method. With regard to GRADE, which stands for Grading of Recommendations, Assessment, Development, and Evaluation, the quality of the evidence will be evaluated. ROBIS Tool will be used to evaluate the risk of bias in the development of the systematic review. If the data is accessible, meta-analysis and dose-response curve analysis will be employed by Stata software. However, if the data does not allow for such analysis, a descriptive review will be performed.Discussion and conclusionHypoglycemic episodes may raise the likelihood of cognitive impairment, according to earlier investigations. This study will update the relevant evidence and explore the dose-response connection between hypoglycemic episodes and cognitive impairment. The results of this review will have significant effects on decision-making by individuals with diabetes, healthcare providers, and government policy institutions.Trial registrationProspero registration number: CRD42023432352.

Objective The purpose of this study was to describe the clinicopathological characteristics and prognosis of primary small cell carcinoma of the breast (PSCCB) and compare PSCCB with breast invasive ductal carcinoma (IDC).Design A retrospective cohort study.Setting Data of patients with PSCCB and breast IDC were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016.Participants Eighty-three patients with PSCCB and 410 699 patients with breast IDC were enrolled in the present cohort study.Materials and methods Patients with PSCCB and breast IDC were identified from the SEER database between 2004 and 2016. The clinicopathological characteristics and survival of patients with PSCCB and IDC were compared. Propensity score matching (PSM) analysis was performed to adjust for differences in baseline characteristics when comparing overall survival (OS) and cancer-specific survival (CSS). Moreover, OS-/CSS-specific nomograms were established to predict the prognosis of PSCCB.Results Compared with IDC, PSCCB was significantly correlated with older age, male, higher pathological grade, higher TNM (tumour, node, metastases) stage, a higher proportion of triple-negative breast cancer, a lower proportion of ER/PR positivity and significantly worse clinical outcome. The median OS and CSS of patients with PSCCB were 23.0 m (95%CI 13.0 to 56.0) and 28.0 m (95%CI 18.0 to 66.0), respectively. The 5-year OS and CSS rates in the PSCCB group were 36.1% and 42.4%, respectively. In the matched cohort after PSM analysis, patients with PSCCB had significantly worse OS and CSS than IDC patients. Multivariate Cox regression analysis demonstrated that T stage and administration of chemotherapy were independent prognostic factors for both OS and CSS in patients with PSCCB. The C-index for OS-/CSS-specific nomogram was 0.75 (95%CI 0.66 to 0.85)/0.79 (95%CI 0.69 to 0.89), respectively. The calibration curve in the ROC analysis indicated that the predicted value was consistent with the actual observation value. Decision curve analysis suggested that the nomogram model has a significant positive net benefit from the risk of death and are better than the traditional TNM staging system.Conclusion PSCCB has distinct clinicopathological characteristics, and patients with PSCCB have significantly worse clinical outcomes than those with IDC.

This paper compares the oral reading errors between the contextual sentences and random words among schoolchildren. Two sets of reading materials were developed to test the oral reading errors in 30 schoolchildren (10.00±1.44 years). Set A was comprised contextual sentences while Set B encompassed random words. The schoolchildren were asked to read both contextual sentences and random words reading charts at random order, loudly at normal reading speed. The reading errors were quantified based on the number of mistakes made during reading. The errors were classified into 6 categories; mispronunciations, substitutions, refusals, additions, omissions, and reversals. The results indicated the mean number of errors made by schoolchildren in reading sentence of Set A and Set B were 1.30±0.23 words and 2.70±0.41 words respectively. Random words, Set B, gave a significantly higher number of reading errors compared to contextual sentences, Set A, (U=287, z=-2.46, p=0.01). Reading the random words gave higher number of errors compared to reading the contextual sentences. Mispronunciations and substitutions were the most possible types of errors made when reading Set B (U=234, z=-3.60, p=<0.01 and U=325, z=-2.00, p=0.04 respectively). Schoolchildren tended to mispronounce and substitute some words during reading the random words. In comparing the number of oral reading errors made between schoolchildren and young adults, there was no significant difference. A similar pattern of the type of errors was also found in oral reading errors in both schoolchildren and young adults. Overall findings could be linked to the existence of comprehension during reading the contextual sentences compared to reading the random words.

Passages with continuous sentences are commonly used for the assessment of reading performance related to visual function, and rehabilitation in optometric practices. Passages created in native languages are crucial for a reliable interpretation in a real scenario. This study aimed to report the development of SAH Reading Passage Compendium (SAHRPC), as a tool for the assessment of reading performance related to visual function. SAHRPC uses the Malay language as the medium of communication. The development of the SAHRPC encompassed three stages: exploratory, confirmatory and prototyping. In the exploratory stage, 300 sentences were extracted from the standard school textbook (in the Malay language) endorsed by the Ministry of Education, Malaysia. The accumulated reading materials were processed based on two deciding factors: continuous sentence structure and predetermined total number of words. A total of 56 passages were constructed with equal readability, based on a simple "5 continuous sentences structure of 50 words" combination. In the confirmatory stage, the 56 passages were verified by normal sighted native Malay speakers. The reading duration was measured using a stopwatch, while the errors were recorded using an audiotape. Reading speed was quantified in words per minute (wpm). Three passages were first eliminated based on the outliers present in the boxplot graph. Eleven passages were further eliminated based on the 10 % highest error and 5 % of the two extreme ends of the reading speed range. The remaining 42 passages with good reliability were randomly compiled into 3 sets of 13 passages. Thirteen passages in each set were randomly sorted into 13 print sizes, ranged from 1.2 logMAR to 0.0 logMAR. The interchangeability of the 3 sets was inspected and confirmed. A prototype was developed and packaged as the SAHRPC, to be used as a tool for the assessment of reading performance related to visual function, and rehabilitation purposes.

ObjectiveTo investigate the mechanism of RNA-binding protein hnRNP A1 in mouse hippocampal neurons (HT22) on glycolysis.MethodsRIP and CLIP-qPCR were performed by HT22 in vitro to observe the mechanism of hnRNP A1 regulating the expression of key proteins in glycolysis. The RNA binding domain of hnRNP A1 protein in HT22 was inhibited by VPC-80051, and the effect of hnRNP A1 on glycolysis of HT22 was observed. Lentivirus overexpression of hnRNP A1 was used to observe the effect of overexpression of hnRNP A1 on glycolysis of Aβ25–35-injured HT22. The expression of hnRNP A1 in brain tissues of wild-type mice and triple-transgenic (APP/PS1/Tau) AD mice at different ages was studied by Western blot assay.ResultsThe results of RIP experiment showed that hnRNP A1 and HK1 mRNA were significantly bound. The results of CLIP-qPCR showed that hnRNP A1 directly bound to the 2605-2821 region of HK1 mRNA. hnRNP A1 inhibitor can down-regulate the expression of HK1 mRNA and HK1 protein in HT22 cells. Overexpression of hnRNP A1 can significantly reduce the toxic effect of Aβ25–35 on neurons via the hnRNP A1/HK1/ pyruvate pathway. In addition, inhibition of hnRNP A1 binding to amyloid precursor protein (APP) RNA was found to increase Aβ expression, while Aβ25–35 also down-regulated hnRNP A1 expression by enhancing phosphorylation of p38 MAPK in HT22. They interact to form bidirectional regulation, further down-regulating the expression of hnRNP A1, and ultimately aggravating glycolytic dysfunction. Protein immunoblotting showed that hnRNP A1 decreased with age in mouse brain tissue, and the decrease was greater in AD mice, suggesting that the decrease of hnRNP A1 may be a predisposed factor in the pathogenesis of AD.

ObjectiveThis study aimed to provide a realistic observation of survival by major site for 48,866 cancer patients treated at a tertiary cancer hospital in a rural area of China.MethodsPatients with cancer registered between 2007 and 2017 in the Nantong rural area were followed up. The starting date for survival calculation was the date of the first diagnosis of cancer at the Nantong Tumor Hospital, and the closing date was December 31, 2020. Observed survival (OS) was analyzed according to ICD-10 site, sex, age, region, and hospitalization period using the life table method and compared using the Wilcoxon (Gehan) statistic.ResultsThe overall 5-year OS rate was 40.48% for all 48,866 patients, 30.19% for males, and 51.90% for females. The top five cancer sites, accounting for 60.51% of the total cases, were the esophagus, lung, stomach, liver, and cervix, with 5-year OS rates of 33.72%, 18.64%, 32.10%, 19.04%, and 71.51%, respectively. The highest 5-year OS was observed in the thyroid (87.52%) and the lowest was in the pancreas (6.37%). Survival was significantly higher in younger patients than in older patients, with 5-year OSs of 69.26% and 19.84% in those aged 20-29 and 90-99 years, respectively. Five-year OSs improved significantly from 39.35% in 2007-2011 to 41.26% in 2012-2017.ConclusionOverall survival improved over the years, although the improvement at some sites was not significant. The observed survival varies from region to region, reflecting differences in the patterns of major sites, disparities in proportions of hospitalization, and demographic characteristics.

Immune checkpoint inhibitors (ICIs) are an integral antitumor therapy for many malignancies. Most patients show very good tolerability to ICIs; however, serious immune-related adverse events (irAEs) with ICIs have been well documented and prevent some patients from continuing ICIs or even become the direct cause of patient death. Cytopenia is a rare irAE but can be life-threatening. Here, we present the case of a 66-year-old male patient with metastatic lung adenocarcinoma who received two doses of chemotherapy + PD-1 antibody tislelizumab and developed pancytopenia after each dose. Although the first episode of pancytopenia resolved with a treatment regimen of granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), and red blood cell and platelet transfusion, the second episode showed extreme resistance to these treatments and improved only after the administration of steroids. His second pancytopenia episode resolved after a long course of treatment with methylprednisolone, G-CSF, TPO, hetrombopag and multiple red blood cell and platelet transfusions. However, he suffered a cerebral infarction when his platelet count was in the normal range and gradually recovered 1 week later. This case highlights the importance of the early recognition and management of hematological irAEs.

‘Candidatus Liberibacter asiaticus (CLas)’, which causes citrus Huanglongbing (HLB) disease, has not been successfully cultured in vitro to date. Here, a rapid multiplication system for CLas was established through in vitro regeneration of axillary buds from CLas-infected ‘Changyecheng’ sweet orange (Citrus sinensis Osbeck). Stem segments with a single axillary bud were cultured in vitro to allow CLas to multiply in the regenerating axillary buds. A high CLas titer was detected in the regenerated shoots on an optimized medium at 30 days after germination (DAG). This titer was 28.2-fold higher than in the midribs from CLas-infected trees growing in the greenhouse. To minimize contamination during in vitro regeneration, CLas-infected axillary buds were micrografted onto seedlings of ‘Changyecheng’ sweet orange and cultured in a liquid medium. In this culture, the titers of CLas in regenerated shoots rapidly increased from 7.5×104 to 1.4×108 cells μg–1 of citrus DNA during the first 40 DAG. The percentages of shoots with >1×108 CLas cells μg–1 DNA were 30 and 40% at 30 and 40 DAG, respectively. Direct tissue blot immunoassay (DTBIA) indicated that the distribution of CLas was much more uniform in regenerated plantlets than in CLas-infected trees growing in the greenhouse. The disease symptoms in the plantlets were die-back, stunted growth, leaf necrosis/yellowing, and defoliation. The death rate of the plantlets was 82.0% at 60 DAG. Our results show that CLas can effectively multiply in citrus plantlests in vitro. This method will be useful for studying plant-HLB interactions and for rapid screening of therapeutic compounds against CLas in citrus.