bluuebunny/crossref_metadata_2025 huggingface dataset:
The oldest unvaccinated Covid-19 survivors in South America
Authors: de Castro Mateus V. , Silva Monize V. R. , Naslavsky Michel S. , Scliar Marilia O. , Nunes Kelly , Passos-Bueno Maria Rita , Castelli Erick C. , Magawa Jhosiene Y. , Adami Flávia L. , Moretti Ana I. S. , de Oliveira Vivian L. , Boscardin Silvia B. , Cunha-Neto Edecio , Kalil Jorge , Jouanguy Emmanuelle , Bastard Paul , Casanova Jean-Laurent , Quiñones-Vega Mauricio , Sosa-Acosta Patricia , Guedes Jéssica de S. , de Almeida Natália P. , Nogueira Fábio C. S. , Domont Gilberto B. , Santos Keity S. , Zatz Mayana
Published: November 2022

Background

Although older adults are at a high risk of severe or critical Covid-19, there are many cases of unvaccinated centenarians who had a silent infection or recovered from mild or moderate Covid-19. We studied three Brazilian supercentenarians, older than 110 years, who survived Covid-19 in 2020 before being vaccinated.

Results

Despite their advanced age, humoral immune response analysis showed that these individuals displayed robust levels of IgG and neutralizing antibodies (NAbs) against SARS-CoV-2. Enrichment of plasma proteins and metabolites related to innate immune response and host defense was also observed. None presented autoantibodies (auto-Abs) to type I interferon (IFN). Furthermore, these supercentenarians do not carry rare variants in genes underlying the known inborn errors of immunity, including particular inborn errors of type I IFN.

Conclusion

These observations suggest that their Covid-19 resilience might be a combination of their genetic background and their innate and adaptive immunity.
The diseased kidney: aging and senescent immunology
Authors: Chi Mingxuan , Tian Zijun , Ma Kuai , Li Yunlong , Wang Li , Nasser Moussa Ide , Liu Chi
Published: November 2022

Immunosenescence is the deterioration of the innate and adaptive immune systems associated with aging and is primarily characterized by a reduction in T cell production and accumulation of atypical subsets. Age-related immunological dysfunction leads to impaired immune protection and persistent low-grade chronic inflammation, resulting in a decreased vaccination response and increased vulnerability to infection, cancer, cardiovascular disease, and autoimmune disease in the elderly. As the elderly constitute a growing proportion of the population with renal disease, immunosenescence is a normal aging process that is prevalent among older people. In addition, immunosenescence seems to be more pronounced in patients with kidney diseases than in healthy controls, as shown by severe chronic inflammation, accumulation of immune cells with the senescent phenotype (CD28− T cells, CD14+CD16+ monocytes), and proinflammatory cytokine production. Immunosenescence inhibits immunological clearance and renal tissue regeneration, thereby increasing the risk of permanent renal damage, infection, and cardiovascular events in patients with kidney disease, lowering the prognosis, and even influencing the efficacy of renal replacement treatment. Biological drugs (senomorphics and senolytics) target the aging immune system and exert renoprotective effects. This review aims to emphasize the features of immunosenescence and its influence on kidney diseases and immunotherapy, highlighting the future directions of kidney disease treatment using senescence-focused techniques.
Nematocyst sequestration within the family Fionidae (Gastropoda: Nudibranchia) considering ecological properties and evolution
Authors: Ekimova Irina A. , Vorobyeva Olga A. , Mikhlina Anna L. , Schepetov Dimitry M. , Vortsepneva Elena V. , Antokhina Tatiana I. , Malakhov Vladimir V.
Published: November 2022

Aeolid nudibranchs are well-known for their ability to incorporate cnidarian nematocysts and use them for defense; this process is tightly linked with the feeding preferences of molluscs. As many nudibranch groups show signs of ecology-based adaptive radiation, studies of prey-based defensive mechanisms can provide valuable insight into details of nudibranch evolutionary history. The main goal of this study is to test the correlation of ecological traits, feeding mechanisms, and prey preferences with cnidosac fine morphology and to pinpoint the phylogenetic value of these traits.We study the cnidosac morphology in thirteen species—representatives of the main lineages within the family Fionidaes.l.The morphological analysis includes histological sections, transmission electron microscopy, confocal laser scanning microscopy, and scanning electron microscopy. For phylogenetic study, available molecular data from public repositories were used, and phylogenetic trees were produced based on Bayesian Inference and Maximum likelihood analysis for a concatenated dataset of three molecular markers (COI, 16S, H3). In general, fionid cnidosacs fit the common aeolid pattern, but among different species we detected a high variation in type of obtained nematocysts, their arrangement within cnidophages, and in number of cell types within cnidosacs. We report on presence ofcellules specialein the haemocoel of all studied species, and for the first time, we report on cells with chitinous spindles in the haemocoel of all fionids exceptEubranchus.The function of both these cell types remains unknown. The loss of functional cnidosacs occurred at least three times within Fionidae, and in case of the generaPhestilla, Calma,andFiona,this loss is linked to their non-cnidarian diet. The diversity of cnidosac fine structure within Fionidaes.l.correlates with that of the radular morphology and feeding preferences of each species. Prey shifts between cnidarian and non-cnidarian prey (both through evolutionary shifts and individual variation) rarely occur within Fionidaes.l.;however, microevolutionary shifts between different hydrozoan species within a single genus are more common. Cnidosac morphology demonstrates considerable resulting changes even when switching between similar hydrozoan species, or changing the feeding site on same prey species. These data indicate that cnidosac morphology likely follows microevolutionary prey shifts—in other words, it is affected by switches in prey species and changes in feeding sites with a single prey species. Thus, the cnidosac morphology may be a useful indicator when studying ecological features of particular species.
Automated patient-robot assignment for a robotic rehabilitation gym: a simplified simulation model
Authors: Miller Benjamin A. , Adhikari Bikranta , Jiang Chao , Novak Vesna D.
Published: November 2022

Background

A robotic rehabilitation gym can be defined as multiple patients training with multiple robots or passive sensorized devices in a group setting. Recent work with such gyms has shown positive rehabilitation outcomes; furthermore, such gyms allow a single therapist to supervise more than one patient, increasing cost-effectiveness. To allow more effective multipatient supervision in future robotic rehabilitation gyms, we propose an automated system that could dynamically assign patients to different robots within a session in order to optimize rehabilitation outcome.

Methods

As a first step toward implementing a practical patient-robot assignment system, we present a simplified mathematical model of a robotic rehabilitation gym. Mixed-integer nonlinear programming algorithms are used to find effective assignment and training solutions for multiple evaluation scenarios involving different numbers of patients and robots (5 patients and 5 robots, 6 patients and 5 robots, 5 patients and 7 robots), different training durations (7 or 12 time steps) and different complexity levels (whether different patients have different skill acquisition curves, whether robots have exit times associated with them). In all cases, the goal is to maximize total skill gain across all patients and skills within a session.

Results

Analyses of variance across different scenarios show that disjunctive and time-indexed optimization models significantly outperform two baseline schedules: staying on one robot throughout a session and switching robots halfway through a session. The disjunctive model results in higher skill gain than the time-indexed model in the given scenarios, and the optimization duration increases as the number of patients, robots and time steps increases. Additionally, we discuss how different model simplifications (e.g., perfectly known and predictable patient skill level) could be addressed in the future and how such software may eventually be used in practice.

Conclusions

Though it involves unrealistically simple scenarios, our study shows that intelligently moving patients between different rehabilitation robots can improve overall skill acquisition in a multi-patient multi-robot environment. While robotic rehabilitation gyms are not yet commonplace in clinical practice, prototypes of them already exist, and our study presents a way to use intelligent decision support to potentially enable more efficient delivery of technologically aided rehabilitation.
CT radiomics-based long-term survival prediction for locally advanced non-small cell lung cancer patients treated with concurrent chemoradiotherapy using features from tumor and tumor organismal environment
Authors: Chen Nai-Bin , Xiong Mai , Zhou Rui , Zhou Yin , Qiu Bo , Luo Yi-Feng , Zhou Su , Chu Chu , Li Qi-Wen , Wang Bin , Jiang Hai-Hang , Guo Jin-Yu , Peng Kang-Qiang , Xie Chuan-Miao , Liu Hui
Published: November 2022

Background

Definitive concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced non-small cell lung cancer (LANSCLC) patients, but the treatment response and survival outcomes varied among these patients. We aimed to identify pretreatment computed tomography-based radiomics features extracted from tumor and tumor organismal environment (TOE) for long-term survival prediction in these patients treated with CCRT.

Methods

A total of 298 eligible patients were randomly assigned into the training cohort and validation cohort with a ratio 2:1. An integrated feature selection and model training approach using support vector machine combined with genetic algorithm was performed to predict 3-year overall survival (OS). Patients were stratified into the high-risk and low-risk group based on the predicted survival status. Pulmonary function test and blood gas analysis indicators were associated with radiomic features. Dynamic changes of peripheral blood lymphocytes counts before and after CCRT had been documented.

Results

Nine features including 5 tumor-related features and 4 pulmonary features were selected in the predictive model. The areas under the receiver operating characteristic curve for the training and validation cohort were 0.965 and 0.869, and were reduced by 0.179 and 0.223 when all pulmonary features were excluded. Based on radiomics-derived stratification, the low-risk group yielded better 3-year OS (68.4% vs. 3.3%, p < 0.001) than the high-risk group. Patients in the low-risk group had better baseline FEV1/FVC% (96.3% vs. 85.9%, p = 0.046), less Grade ≥ 3 lymphopenia during CCRT (63.2% vs. 83.3%, p = 0.031), better recovery of lymphopenia from CCRT (71.4% vs. 27.8%, p < 0.001), lower incidence of Grade ≥ 2 radiation-induced pneumonitis (31.6% vs. 53.3%, p = 0.040), superior tumor remission (84.2% vs. 66.7%, p = 0.003).

Conclusion

Pretreatment radiomics features from tumor and TOE could boost the long-term survival forecast accuracy in LANSCLC patients, and the predictive results could be utilized as an effective indicator for survival risk stratification. Low-risk patients might benefit more from radical CCRT and further adjuvant immunotherapy.

Trial registration:

retrospectively registered.
Correlation and significance of COX-2, Ki67, VEGF and other immune indexes with the growth of malignant pulmonary nodules
Authors: Guo Haoxin , Xue Wenfei , Zhao Qingtao , Zhao Huanfen , Hu Zhonghui , Zhang Xiaopeng , Duan Guochen
Published: November 2022

Objective

This study intends to explore the factors affecting the growth of pulmonary nodules in the natural process by immunohistochemical method.

Methods

40 cases of pulmonary nodules followed up for more than 3 years were divided into growth group (n = 20) and stable group (n = 20). The expressions of cyclooxygenase-2 (COX-2), Ki67, vascular endothelial growth factor (VEGF), CD44V6, epidermal growth factor receptor (EGFR), double microsome 2 (MDM2) and transforming growth factor (TGF)-β1 in pulmonary nodules were detected by immunohistochemical method so as to explore the relationship between it and the growth of pulmonary nodules.

Results

Compared with stable pulmonary nodules, the positive rates of COX-2, Ki67 and VEGF in the growth group were 85%, 80% and 55%, respectively. There was significant difference between the stable group and the growth group (P < 0.05). The correlation between other indexes and the growth of pulmonary nodules was not statistically significant (Pcd44v6 = 0.104;PEGFR = 0.337; PMDM2 = 0.49; PTGF-β1 = 0.141). In the subgroup of patients with non-invasive lung cancer, there was a correlation between VEGF and the growth of pulmonary nodules (P < 0.05).

Conclusion

The high expression of COX-2, Ki67 and VEGF proteins may be significantly related to the growth of pulmonary nodules, and VEGF may be an important factor affecting the growth of malignant pulmonary nodules. This study intends to provide a research direction for further searching for the essential causes of the growth of pulmonary nodules.
SIRPα-Fc fusion protein IMM01 exhibits dual anti-tumor activities by targeting CD47/SIRPα signal pathway via blocking the “don’t eat me” signal and activating the “eat me” signal
Authors: Yu Jifeng , Li Song , Chen Dianze , Liu Dandan , Guo Huiqin , Yang Chunmei , Zhang Wei , Zhang Li , Zhao Gui , Tu Xiaoping , Peng Liang , Liu Sijin , Bai Xing , Song Yongping , Jiang Zhongxing , Zhang Ruliang , Tian Wenzhi
Published: November 2022

A novel recombinant SIRPα-Fc fusion protein, IMM01, was constructed and produced using an in-house developed CHO-K1 cell expression system, and the anti-tumor mechanism of IMM01 targeting the CD47-SIRPα pathway was explored. The phagocytosis and in vitro anti-tumor activity of IMM01 were evaluated by antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC) assays. In vivo mouse tumor model studies were used to explore therapeutic efficacy as well as the mechanism of action. An in vitro binding assay revealed that IMM01 has a strong binding affinity to CD47 with an EC50 of 0.4967 nM. IMM01 can induce strong ADCP and moderate ADCC, but not CDC. IMM01-induced strong phagocytosis against tumor cells was attributed to dual activities of blocking the "don’t eat me" signal and activating the "eat me" signal, and IMM01 exhibits strong and robust in vivo anti-tumor activities either as monotherapy on hematological malignancies, or in combination therapy with PD-L1 monoclonal antibody (mAb), PD-1 mAb, and HER-2 mAb on solid tumors. Finally, IMM01 demonstrated a favorable safety profile with no human RBC binding activity or hemagglutination induction. IMM01 inhibits the growth of tumor cells by the following three possible mechanisms: (1) directly activating macrophages to phagocytize tumor cells; (2) activated macrophages degrade phagocytized tumor cells and present tumor antigens to T cells through MHC molecules to activate T cells; (3) activated macrophages can convert "cold tumors" into "hot tumors" and increase the infiltration of immune cells through chemotaxis by secreting some cytokines and chemokines.
ARPC1B promotes mesenchymal phenotype maintenance and radiotherapy resistance by blocking TRIM21-mediated degradation of IFI16 and HuR in glioma stem cells
Authors: Gao Zijie , Xu Jianye , Fan Yang , Zhang Zongpu , Wang Huizhi , Qian Mingyu , Zhang Ping , Deng Lin , Shen Jie , Xue Hao , Zhao Rongrong , Zhou Teng , Guo Xing , Li Gang
Published: November 2022

Background

Intratumoral heterogeneity is the primary challenge in the treatment of glioblastoma (GBM). The presence of glioma stem cells (GSCs) and their conversion between different molecular phenotypes contribute to the complexity of heterogeneity, culminating in preferential resistance to radiotherapy. ARP2/3 (actin-related protein-2/3) complexes (ARPs) are associated with cancer migration, invasion and differentiation, while the implications of ARPs in the phenotype and resistance to radiotherapy of GSCs remain unclear.

Methods

We screened the expression of ARPs in TCGA-GBM and CGGA-GBM databases. Tumor sphere formation assays and limiting dilution assays were applied to assess the implications of ARPC1B in tumorigenesis. Apoptosis, comet, γ-H2AX immunofluorescence (IF), and cell cycle distribution assays were used to evaluate the effect of ARPC1B on radiotherapy resistance. Immunoprecipitation (IP) and mass spectrometry analysis were used to detect ARPC1B-interacting proteins. Immune blot assays were performed to evaluate protein ubiquitination, and deletion mutant constructs were designed to determine the binding sites of protein interactions. The Spearman correlation algorithm was performed to screen for drugs that indicated cell sensitivity by the expression of ARPC1B. An intracranial xenograft GSC mouse model was used to investigate the role of ARPC1B in vivo.

Results

We concluded that ARPC1B was significantly upregulated in MES-GBM/GSCs and was correlated with a poor prognosis. Both in vitro and in vivo assays indicated that knockdown of ARPC1B in MES-GSCs reduced tumorigenicity and resistance to IR treatment, whereas overexpression of ARPC1B in PN-GSCs exhibited the opposite effects. Mechanistically, ARPC1B interacted with IFI16 and HuR to maintain protein stability. In detail, the Pyrin of IFI16 and RRM2 of HuR were implicated in binding to ARPC1B, which counteracted TRIM21-mediated degradation of ubiquitination to IFI16 and HuR. Additionally, the function of ARPC1B was dependent on IFI16-induced activation of NF-κB pathway and HuR-induced activation of STAT3 pathway. Finally, we screened AZD6738, an ataxia telangiectasia mutated and rad3-related (ATR) inhibitor, based on the expression of ARPC1B. In addition to ARPC1B expression reflecting cellular sensitivity to AZD6738, the combination of AZD6738 and radiotherapy exhibited potent antitumor effects both in vitro and in vivo.

Conclusion

ARPC1B promoted MES phenotype maintenance and radiotherapy resistance by inhibiting TRIM21-mediated degradation of IFI16 and HuR, thereby activating the NF-κB and STAT3 signaling pathways, respectively. AZD6738, identified based on ARPC1B expression, exhibited excellent anti-GSC activity in combination with radiotherapy.
Neoantigen-specific TCR-T cell-based immunotherapy for acute myeloid leukemia
Authors: Zhou Weijun , Yu Jinyi , Li Yilu , Wang Kankan
Published: November 2022

Neoantigens derived from non-synonymous somatic mutations are restricted to malignant cells and are thus considered ideal targets for T cell receptor (TCR)-based immunotherapy. Adoptive transfer of T cells bearing neoantigen-specific TCRs exhibits the ability to preferentially target tumor cells while remaining harmless to normal cells. High-avidity TCRs specific for neoantigens expressed on AML cells have been identified in vitro and verified using xenograft mouse models. Preclinical studies of these neoantigen-specific TCR-T cells are underway and offer great promise as safe and effective therapies. Additionally, TCR-based immunotherapies targeting tumor-associated antigens are used in early-phase clinical trials for the treatment of AML and show encouraging anti-leukemic effects. These clinical experiences support the application of TCR-T cells that are specifically designed to recognize neoantigens. In this review, we will provide a detailed profile of verified neoantigens in AML, describe the strategies to identify neoantigen-specific TCRs, and discuss the potential of neoantigen-specific T-cell-based immunotherapy in AML.
Beneficial effect of the short-chain fatty acid propionate on vascular calcification through intestinal microbiota remodelling
Authors: Yan Jianlong , Pan Yanbin , Shao Wenming , Wang Caiping , Wang Rongning , He Yaqiong , Zhang Min , Wang Yongshun , Li Tangzhiming , Wang Zhefeng , Liu Wenxing , Wang Zhenmin , Sun Xin , Dong Shaohong
Published: November 2022

Background

Vascular calcification is a major cause of the high morbidity and mortality of cardiovascular diseases and is closely associated with the intestinal microbiota. Short-chain fatty acids (SCFAs) are derived from the intestinal microbiota and can also regulate intestinal microbiota homeostasis. However, it remains unclear whether exogenous supplementation with propionate, a SCFA, can ameliorate vascular calcification by regulating the intestinal microbiota. This study was conducted to explore the roles of propionate and the intestinal microbiota in the process of vascular calcification.

Methods

In total, 92 patients were enrolled consecutively as the observational cohort to analyse the relationship between SCFAs and vascular calcification in both blood and faecal samples. A rat model of vascular calcification was induced by vitamin D3 and nicotine (VDN) to validate the effect of propionate. Differences in the intestinal microbiota were analysed by 16S ribosomal RNA gene sequencing. Faecal microbiota transplantation and Akkermansia muciniphila transplantation experiments were performed to evaluate the functions of the intestinal microbiota.

Results

The results of the observational cohort study revealed that the levels of SCFAs (particularly propionate) in both blood and faecal samples independently correlated negatively with calcification scores (P < 0.01). To verify the activities of propionate, it was provided to VDN-treated rats, and oral or rectal propionate delivery reshaped the intestinal microbiota, resulted in elevated SCFA production, improved intestinal barrier function and alleviated inflammation, ultimately ameliorating vascular calcification. Furthermore, we demonstrated that transplantation of the propionate-modulated intestinal microbiota induced beneficial outcomes similar to those with oral or rectal propionate administration. Interestingly, linear discriminant analysis (LDA) effect size (LEfSe) revealed that oral or rectal propionate administration and propionate-modulated intestinal microbiota transplantation both enriched primarily Akkermansia. Subsequently, we demonstrated that Akkermansia supplementation could ameliorate VDN-induced vascular calcification in rats.

Conclusions

Propionate can significantly ameliorate vascular calcification in VDN-treated rats, and this effect is mediated by intestinal microbiota remodelling. The findings in our study indicate that the intestinal tract-vessel axis is a promising target for alleviating vascular calcification.
Urease and β-glucosidase activity enhanced the transformation of functional groups of humin amended by straw and straw-derived biochar
Authors: Liu Xinwei , An Qi , Song Xiangyun , Hussain Qaiser , Cui Liqiang , Wang Chengji , Wang Yan , Cui Dejie
Published: November 2022

Background

Organic materials carbon is mainly sequestrated in humin. However, the carbon (C) stability of humin with organic materials amendments in different types of soils is mainly affected by organic materials or soil types as well as the enzymatic reaction is important for understanding the C sequestration mechanism of soil.

Results

In this study, straw and straw-derived biochar were incorporated into three different types of soils. Using 13C nuclear magnetic resonance (NMR) spectroscopy, the structural composition of humin (Hu) was analyzed, along with the urease and β-glucosidase activities. The results showed that biochar amendment enhanced aryl C to 49.63%–76.55% while straw amendments increased O-alkyl C of Hu to 33.99%–51.70%. Two-way ANOVA analysis revealed significant differences in the impact of soil types and treatments on enzyme activities and functional groups of humin. A significant positive correlation was found between β-glucosidase activity and O-alkyl C, phenolic C, and methoxyl C of humin. In addition, urease activity showed a significant positive correlation with alkyl C of humin. Compared to tobacco straw, tobacco straw-biochar amendment increased β-glucosidase activity for 22.01 mg kg−1 d−1, 26.01 mg kg−1 d−1 and 14.01 mg kg−1 d−1 in three types of soils, respectively.

Conclusions

These results showed that β-glucosidase contributed to the transformation of humin functional groups and was influenced by organic materials and soil types, especially the organic materials types. The findings imply that straw or straw-derived biochar application stimulates urease and β-glucosidase activities, which improves the alternation of functional groups of humin in different types of soil.

Graphical Abstract
Development and psychometric analysis of a new tool to assess food literacy in diabetic patients
Authors: Bastami Fatemeh , Mardani Mahnaz , Rezapour Pouria
Published: November 2022

Background

One of the factors affecting self-care in diabetic patients is food literacy, which helps said patients in following a healthy diet. Thus, it is crucial to analyze food literacy in diabetic patients through suitable and reliable instruments. 

Objective

The current study aimed to design a questionnaire for food literacy assessment in diabetic patients and analyze its psychometric features.

Method

The present study was a cross-sectional descriptive analysis carried out in 2021. Firstly, the concepts of food literacy in diabetic patients were identified and the questionnaire was deigned based on them. Secondly, its face and content validities and its reliability were analyzed. Finally, the construct validity was analyzed by exploratory factor analysis. The study was carried out on 300 diabetic participants chosen at random via stratified cluster sampling from Health service centers. The exploratory factor analysis was carried out by extracting the main factors and using varimax rotation with eigenvalue values more than 1.

Results

A five-pronged structure accounted for 52.745% of food literacy variance. This included the ability to read food facts, practical ability to group foods, the ability to identify the caloric content of different foods, the ability to understand the effect of food on health, and the ability to prepare a healthy meal. Items with an impact score below 1.5 were discarded. Additionally, items with CVR scores below 0.62 and CVI scores below 0.79 were deleted too. The Kaiser-Meyer-Okin measurement was 0.836 (p < 0.001). Alpha Cronbach Scale dimension was 0.610–0.951.

Conclusion

The results of this study showed that the exploratory dimensions of the current study were consistent with health literacy measurements, such as functional, interactive, and critical food literacy. This scale has acceptable reliability and validity. Health professionals can use this scale to analyze and improve food literacy in diabetic patients. This is a new instrument and thus far no questionnaire has been made to evaluate food literacy in diabetic patients.
Radiotherapy or Surgery of the Axilla After a Positive Sentinel Node in Breast Cancer: 10-Year Results of the Randomized Controlled EORTC 10981-22023 AMAROS Trial
Authors: Bartels Sanne A.L. , Donker Mila , Poncet Coralie , Sauvé Nicolas , Straver Marieke E. , van de Velde Cornelis J.H. , Mansel Robert E. , Blanken Charlotte , Orzalesi Lorenzo , Klinkenbijl Jean H.G. , van der Mijle Huub C.J. , Nieuwenhuijzen Grard A.P. , Veltkamp Sanne C. , van Dalen Thijs , Marinelli Andreas , Rijna Herman , Snoj Marko , Bundred Nigel J. , Merkus Jos W.S. , Belkacemi Yazid , Petignat Patrick , Schinagl Dominic A.X. , Coens Corneel , van Tienhoven Geertjan , van Duijnhoven Frederieke , Rutgers Emiel J.T.
Published: November 2022

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

PURPOSE

The European Organisation for Research and Treatment of Cancer 10981-22023 AMAROS trial evaluated axillary lymph node dissection (ALND) versus axillary radiotherapy (ART) in patients with cT1-2, node-negative breast cancer and a positive sentinel node (SN) biopsy. At 5 years, both modalities showed excellent and comparable axillary control, with significantly less morbidity after ART. We now report the preplanned 10-year analysis of the axillary recurrence rate (ARR), overall survival (OS), and disease-free survival (DFS), and an updated 5-year analysis of morbidity and quality of life.

METHODS

In this open-label multicenter phase III noninferiority trial, 4,806 patients underwent SN biopsy; 1,425 were node-positive and randomly assigned to either ALND (n = 744) or ART (n = 681).

RESULTS

Per intention-to-treat analysis, 10-year ARR cumulative incidence was 0.93% (95% CI, 0.18 to 1.68; seven events) after ALND and 1.82% (95% CI, 0.74 to 2.94; 11 events) after ART (hazard ratio [HR], 1.71; 95% CI, 0.67 to 4.39). There were no differences in OS (HR, 1.17; 95% CI, 0.89 to 1.52) or DFS (HR, 1.19; 95% CI, 0.97 to 1.46). ALND was associated with a higher lymphedema rate in updated 5-year analyses (24.5% v 11.9%; P < .001). Quality-of-life scales did not differ by treatment through 5 years. Exploratory analysis showed a 10-year cumulative incidence of second primary cancers of 12.1% (95% CI, 9.6 to 14.9) after ART and 8.3% (95% CI, 6.3 to 10.7) after ALND.

CONCLUSION

This 10-year analysis confirms a low ARR after both ART and ALND with no difference in OS, DFS, and locoregional control. Considering less arm morbidity, ART is preferred over ALND for patients with SN-positive cT1-2 breast cancer.
Periodic solution of the parametric Gaylord's oscillator with a non-perturbative approach
Authors: El-Dib Yusry O. , Elgazery Nasser S.
Published: November 2022

The vibration of a regular rigid bar without sliding over a solid annular surface of a specified radius can be considered by a parametric Gaylord's oscillator. The governing equation was the result of a strong nonlinear oscillation without having a natural frequency. The present work is concerned with obtaining the approximate solution and amplitude-frequency equation of the parametric Gaylord's equation via an easier process. The non-perturbative approach was applied twice to analyze the present oscillator. Two steps are used, the first is to transform Gaylord's oscillator to the parametric pendulum equation having a natural frequency. The second step is to establish the amplitude-frequency relationship which was taken out in terms of the Bessel functions. A periodic analytic solution is obtained, in the presence or without the parametric force. The frequency at the resonance case is established without a perturbation for the first time. The stability condition is established and discussed graphically. The analytic solution was also validated by comparing it with its corresponding numerical data which showed a very good agreement. In a word, by dissection of the behavior of strong nonlinearity oscillators, the non-perturbative technique is characterized by its ease and simplicity along with high accuracy when compared to other perturbative methods.
Heterogeneous phase oscillators encoded by simplexes under coupling strength symmetry breaking: Optimal synchronization and abrupt desynchronization
Authors: Liu Xiangdong
Published: November 2022

Recent advances demonstrate that the collective dynamics of heterogeneous phase oscillators ensemble encoded by simplexes play an important role in the storage of information in the human brain. In this letter, we discuss the collective dynamics of heterogeneous phase oscillator networks encoded by simplexes under coupling strength symmetry breaking. Specifically, the strength of the asymmetric coupling between the oscillators is redefined by the degree of the oscillators under 1- and 2-simplex encoding and the heterogeneity parameter. Here, we discuss the effect of different degrees of coupling strength symmetry breaking on the synchronization capability of the system. In particular, we find that proper coupling strength symmetry breaking is beneficial to enhance the synchronization capability of the system. We capture an interesting phenomenon in heterogeneous phase oscillator networks that distinguish symmetric coupling under 1- and 2-simplex encoding, i.e., the system exhibits significant desynchronization behavior under strong symmetry breaking of the coupling strength. Finally, for a fixed heterogeneity parameter and coupling strength assignment probability, we give the optimal intrinsic frequency assignment scheme based on the spectral decomposition of the composite Laplace matrix of the underlying network. Theoretically, these findings may help us to better understand the collective dynamics in heterogeneous phase oscillator networks encoded by simplexes under asymmetric coupling that are prevalent in the real world. In particular, they provide inspiration and guidance for optimizing the synchronization of heterogeneous phase oscillator networks encoded by simplexes under coupling strength symmetry breaking.
Ultrabroad reflective polarization converter in terahertz based on circular-end graphene rectangles
Authors: Ding Yuzhuo , Chang Yunwei , Yao Jie
Published: November 2022

Polarization is one of the basic properties of electromagnetic waves. Control and manipulation of polarization by devices based on metasurfaces have versatile applications in modern technologies. We propose a broadband reflective cross-polarization converter in the THz region based on an array of circular-end graphene rectangular patches. Efficient polarization conversion was accomplished through dipole graphene plasmon resonances (DGPRs), either along the long or the short axis of the graphene patches. As the width of the rectangles increased, a new longitudinal dipole mode appeared due to the circular ends of the patches. It grew strong and connected the original DGPRs, constructing an ultrabroad conversion band with efficiency over 94% from approximately 2.5 to 5.0 THz. The relative bandwidth was nearly 66%, surpassing most broadband converters reported. Such broad conversion held for a wide incident angle range as DGPRs were robust to the direction of irradiation. Due to the adjustable optical properties of graphene, the broad conversion band can be tuned. These findings are inspiring for creating broadband, compact and dynamic optoelectrical devices in the THz range.
Adaptive altruistic strategy in cyclic models during an epidemic
Authors: Menezes J. , Ferreira B. , Rangel E. , Moura B.
Published: November 2022

We investigate a cyclic game system where organisms face an epidemic beyond being threatened by natural enemies. As a survival strategy, individuals of one out of the species usually safeguard themselves by approaching the enemies of their enemies and performing social distancing to escape contamination when an outbreak affects the neighbourhood. We simulate how the survival movement strategy to local epidemic surges must adapt if a pathogen mutation makes the disease deadlier. We study the spatial distribution of local outbreaks and observe the influence of disease mortality on individuals' spatial organisation. We show that adapting the survival movement strategy for a high-mortality disease demands an altruistic behaviour of the organisms since their death risk increases. Despite weakening the disease transmission chain, which benefits the species, abandoning refuges provided by safeguarding social interaction increases the vulnerability to being eliminated in the cyclic game. Considering that not all individuals exhibit altruism, we find the relative growth in the species density as a function of the proportion of individuals behaving altruistically. Our results may be helpful for biologists and data scientists to understand how adaptive altruistic processes can affect population dynamics in complex systems.
Duration of Diabetes, Glycemic Control, and Risk of Heart Failure Among Adults With Diabetes: A Cohort Study
Authors: Yang Huan-Huan , Li Fu-Rong , Chen Ze-Kun , Zhou Meng-Ge , Xie Li-Feng , Jin Yuan-Yuan , Li Zhi-Hui , Chen Guo-Chong
Published: November 2022

Context

The influences of diabetes duration and glycemic control and their potential interplays on the risk of heart failure (HF) remain unclear.

Objective

This work aimed to investigate the association of diabetes duration and glycemic control with the risk of HF.

Methods

A total of 23 754 individuals with diabetes but without HF during the baseline recruitment of UK Biobank were included in this study. Duration of diabetes was self-reported, and the status of glycemic control was reflected by glycated hemoglobin A1c (HbA1c) levels. Their associations with incident HF were assessed using multivariate Cox models adjusting for traditional risk factors.

Results

Duration of diabetes and HbA1c levels both were positively associated with the risk of HF. The hazard ratios (HRs) (95% CI) for diabetes durations of 5 to less than 10, 10 to less than 15, and 15 years or more were 1.09 (0.97-1.23), 1.13 (0.97-1.30), and 1.32 (1.15-1.53), respectively (vs < 5 years); and the HRs for HbA1c of 53.0 to less than 58.5 mmol/mol (7.0% to < 7.5%), 58.5 to less than 63.9 mmol/mol (7.5% to < 8.0%), and 63.9 mmol/mol or greater (8.0%) were 1.15 (1.02-1.31), 1.07 (0.91-1.26), and 1.46 (1.30-1.65), respectively (vs < 53.0 mmol/mol [7.0%]). Individuals with the longest disease duration (≥ 15 years) and poorer glycemic control (HbA1c ≥ 63.9 mmol/mol [8.0%]) had a particularly higher risk of HF (P for interaction = .026).

Conclusion

The risk of HF among individuals with diabetes increases with a longer duration of diabetes and increasing HbA1c levels. This finding may contribute to the individualized prevention of HF in patients with diabetes if being considered in clinical practices and policy-making.
Improving Preclinical Development of Novel Interventions to Treat Pain: Insanity Is Doing the Same Thing Over and Over and Expecting Different Results
Authors: Eisenach James C. , Rice Andrew S. C.
Published: November 2022

Preclinical pain research has applied state-of-the-art methods over the past 40 years to describe, characterize, and image molecules, cells, and circuits in rodents to understand the pathophysiology of chronic pain. Despite generating a plethora of novel analgesic targets, pharmaceuticals for chronic pain treatment remain largely limited to the same 6 drug classes as present 40 years ago. It is possible that 40 years of effort has brought us to the verge of a paradigm shift and an explosion of novel analgesic drug classes with remarkable safety, efficacy, and tolerability. We think it more likely that advances will not occur until we follow the description of exciting discoveries with hypothesis testing using clinically relevant preclinical animal models and ethologically relevant outcome measures, which better reflect the clinical characteristics of chronic pain syndromes. Furthermore, to be valuable, experiments using such models must be conducted to the highest levels of internal validity, rigor, and reproducibility. Efforts by funders, most recently the Helping End Addiction Long-Term by the National Institutes of Health, aim to address some of these challenges and enhance communication and collaboration between preclinical and clinical investigators. However, the greater problem is a culture that emphasizes novelty and number of publications over scientific rigor and robust replication leading to a high likelihood of false-positive results. A path forward is provided by the evolution of clinical research beginning 50 years ago that resulted in methods to reduce bias and enhance transparency and ethics of reporting, moving from case reports to randomized controlled trials to innovative study designs with a focus on rigor, generalizability, and reproducibility. We argue that culture changed in clinical science in part because powerful forces outside the peer review system, especially from federal regulators that approve new drugs and human studies committees that addressed ethical failures of earlier research, mandated change in studies within their purview. Whether an external force will affect change in peclinical pain research is unclear.
State Immigration Policy Contexts and Racialized Legal Status Disparities in Health Care Utilization Among U.S. Agricultural Workers
Authors: Schut Rebecca Anna , Boen Courtney
Published: November 2022

Research links restrictive immigration policies to immigrant health and health care outcomes. Yet most studies in this area focus on the impact of single policies in particular years, with few assessing how broader state-level immigration policy contexts affect groups by nativity, race/ethnicity, and legal status. Linking data from the National Agricultural Workers Survey (2005–2012) with information on state immigration policies, we use an intersectional approach to examine the links between policy contexts and health care utilization by nativity, race/ethnicity, and legal status. We also assess the associations between two specific types of state immigration policies—those governing immigrant access to Medicaid and driver's licenses—and health care utilization disparities. We find that state-level immigration policy contexts are associated with health care utilization among U.S.-born and naturalized U.S. citizen non-White Latinx agricultural workers, who report lower levels of health care utilization and greater barriers to care-seeking in more restrictive policy contexts. By contrast, we find little evidence that state policies shaped health care utilization among undocumented workers. These findings advance understanding of the impact of “policies of exclusion” on the lives of marginalized groups and underscore the importance of racialized legal status in considering the links between sociopolitical contexts and health and health care disparities.
Choreographing the motor-driven endosomal dance
Authors: Jongsma Marlieke L. M. , Bakker Nina , Neefjes Jacques
Published: November 2022

The endosomal system orchestrates the transport of lipids, proteins and nutrients across the entire cell. Along their journey, endosomes mature, change shape via fusion and fission, and communicate with other organelles. This intriguing endosomal choreography, which includes bidirectional and stop-and-go motions, is coordinated by the microtubule-based motor proteins dynein and kinesin. These motors bridge various endosomal subtypes to the microtubule tracks thanks to their cargo-binding domain interacting with endosome-associated proteins, and their motor domain interacting with microtubules and associated proteins. Together, these interactions determine the mobility of different endosomal structures. In this Review, we provide a comprehensive overview of the factors regulating the different interactions to tune the fascinating dance of endosomes along microtubules.
Sonographic and elastographic findings after arthroscopic rotator cuff repair: a comparison with clinical results
Authors: Kim Ji Na , Park Hee Jin , Kim Myung Sub , Choi Yoon Jung , Kim Eugene , Park Jai Hyung , Hong Seok Woo
Published: November 2022

Objective:

We assessed the relationship between early postoperative clinical outcomes of arthroscopic rotator cuff repair (ARCR) and observations obtained by postsurgical ultrasound (US) and strain elastography (SE) of repaired supraspinatus tendons (SSTs).

Methods:

This retrospective study included 42 cases in which the patient underwent ARCR followed by postoperative US and SE. The Korean Shoulder Scoring (KSS) system was used to assess preoperative and postoperative conditions. The thickness of the repaired SST and subdeltoid fluid was measured by US. SE scores were classified into four grades (1 to 4) according to elasticity of repaired SST. In addition, SE scores were divided into two groups: soft (SE scores of 1 and 2) and hard (SE scores of 3 and 4). The relationship between clinical outcomes and US parameters and SE scores was determined by KSS.

Results:

Postoperative SE scores observed by two readers correlated significantly with function (p = 0.021 and p = 0.021, respectively) and muscle strength (p = 0.008 and p = 0.015, respectively). SE scores were significantly correlated with a difference value of muscle strength of KSS scores (p = 0.002 and p = 0.014). In a comparison of hard and soft groups of repaired SSTs, function (p = 0.008 and p = 0.010, respectively) and muscle strength (p = 0.002 and p = 0.014, respectively) in postoperative KSS scores were statistically higher in the hard SE scores than the soft SE scores. The difference value of function (p = 0.021 and p = 0.021,) and muscle strength (p = 0.008 and p = 0.015) of KSS scores was significantly higher in the hard SE scores.

Conclusions:

Postoperative SE scores of repaired tendons correlated significantly with muscle strength and function after ARCR. Postoperative US images including thickness of repaired tendon and subdeltoid fluid did not correlate with clinical outcome.

Advances in knowledge:

SE evaluations of repaired SST may provide important information about postoperative muscle strength and function.
Prevalence of Lipohypertrophy and its Associations in Insulin-Treated Diabetic Patients
Authors: Nawaz Arsalan , Hasham Muhammad Adnan , Shireen Maria , Mehwish Iftikhar
Published: November 2022

Background and Objectives: Lipohypertrophy is a major complications of insulin therapy especially attributed to incorrect insulin technique. The objective was to determine the frequency of lipohypertrophy in diabetic population on insulin and its associations.

Methods: This cross-sectional study was conducted at the Services Hospital Lahore from July 1st, 2020 to December 31st, 2020. Total of 363 diabetic patients, fulfilling the inclusion criteria were approached. The patients were examined and interviewed through a validated questionnaire. The data was stratified according to the age, gender, duration of diabetes, duration of insulin use, frequency of LH and duration since last instructions reviewed. The chi-square test was applied. Data was analyzed using SPSS 22.

Results: Mean age of the study population was 49.71± 13.36 years. Majority were females (57.6%). LH was noted in 22.86% of participants (n=83). There was significant statistical difference noted (P <0.05) between different age groups as 29.7 % of patients in age group above 45 had LH as compared to 19.6% in the below 45 years age group. More females (28.2%) were having LH than the males (15.6%) with P<0.05. Also, significant difference was noted for needle reuse more than 10 times, more than two injections per day and longer duration since last instructions reviewed. No significant difference was noted between different devices for injection as well as for duration of diabetes. LH is strongly associated with hypoglycemia and hyperglycemia with P<0.05.

Conclusion: A significant diabetic population on insulin has noted to have LH, and the risk is more with aged population, female gender, more injections per day and multiple time needle reuses. Risk of LH can be reduced by reinforcing education.

doi: https://doi.org/10.12669/pjms.39.1.6134

How to cite this: Nawaz A, Hasham MA, Shireen M, Iftikhar M. Prevalence of Lipohypertrophy and its Associations in Insulin-Treated Diabetic Patients. Pak J Med Sci. 2023;39(1):---------. doi: https://doi.org/10.12669/pjms.39.1.6134

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.