tbuckley/cabot-search huggingface dataset:
Injectable bone cements: What benefits the combination of calcium phosphates and bioactive glasses could bring?
Authors: Öznur Demir-Oğuz, Aldo R. Boccaccini, Dagnija Loca
Journal: Bioactive Materials (2022)

Out of the wide range of calcium phosphate (CaP) biomaterials, calcium phosphate bone cements (CPCs) have attracted increased attention since their discovery in the 1980s due to their valuable properties such as bioactivity, osteoconductivity, injectability, hardening ability through a low-temperature setting reaction and moldability. Thereafter numerous researches have been performed to enhance the properties of CPCs. Nonetheless, low mechanical performance of CPCs limits their clinical application in load bearing regions of bone. Also, the in vivo resorption and replacement of CPC with new bone tissue is still controversial, thus further improvements of high clinical importance are required. Bioactive glasses (BGs) are biocompatible and able to bond to bone, stimulating new bone growth while dissolving over time. In the last decades extensive research has been performed analyzing the role of BGs in combination with different CaPs. Thus, the focal point of this review paper is to summarize the available research data on how injectable CPC properties could be improved or affected by the addition of BG as a secondary powder phase. It was found that despite the variances of setting time and compressive strength results, desirable injectable properties of bone cements can be achieved by the inclusion of BGs into CPCs. The published data also revealed that the degradation rate of CPCs is significantly improved by BG addition. Moreover, the presence of BG in CPCs improves the in vitro osteogenic differentiation and cell response as well as the tissue-material interaction in vivo.
Charting a Path Towards Asian American Cancer Health Equity: A Way Forward
Authors: Moon S Chen, Richard J Lee, Ravi A Madan, Van Ta Park, Susan M Shinagawa, Tracy Sun, Scarlett L Gomez
Journal: JNCI Journal of the National Cancer Institute (2022)

On July 29, 2021, the US Food and Drug Administration's Oncology Center of Excellence convened Conversations on Cancer. This Conversation, the first ever by the US Food and Drug Administration, focused on Asian Americans and served as the platform for this Commentary. Panelists elaborated on topics ranging from heterogeneity in Asian American demographics to racism through a path to health equity and supplemented this Commentary with literature citations. Asian Americans are the fastest-growing US race group, yet data aggregation obscures distinctions and cancer disparities within the more than 24 million Asians living in the United States with harmful impacts on communities and patients, as illustrated by breast cancer survivor Susan Shinagawa's patient-to-advocate journey. Bigotry against Asian Americans has been pervasive since the 19th century, but especially during the COVID-19 pandemic. Asian Americans are unique as the first US population to experience cancer as the leading cause of death. Asian Americans are disproportionately affected by cancers because of infectious origins and have the highest rates of lung cancer among never-smoking women. The infinitesimal proportion of the National Institutes of Health's budget compared with experiencing the highest percentage increases of any US racial population more than 3 decades highlights the dearth of focused research among Asian Americans. Recognizing the heterogeneity of Asian Americans and that disaggregated data are critical for accurately characterizing distinct ethnic groups, focusing on the impact of racism and COVID-19 on cancer disparities, and focusing and prioritizing funding resources are necessary steps forward for achieving health equity for Asian Americans.
Relationship between NAFLD and coronary artery disease: A Mendelian randomization study
Authors: Zhewen Ren, Pomme I. H. G. Simons, Anke Wesselius, Coen D. A. Stehouwer, Martijn C. G. J. Brouwers
Journal: Hepatology (2022)

Background and Aims: There is an ongoing debate on whether NAFLD is an active contributor or an innocent bystander in the pathogenesis of coronary artery disease (CAD). The aim of the present study was to assess the causal relationship between NAFLD and CAD. Approach and Results: We performed two‐sample Mendelian randomization (MR) analyses using summary‐level data to assess the association between genetically predicted NAFLD (i.e., chronically elevated serum alanine aminotransferase levels [cALT], imaging‐based and biopsy‐confirmed NAFLD) and risk of CAD. Analyses were repeated after exclusion of NAFLD susceptibility genes that are associated with impaired VLDL secretion. Inverse‐variance weighted MR analyses showed a statistically significant association between genetically predicted cALT and risk of CAD (OR: 1.116, 95% CI: 1.039, 1.199), but not for the other NAFLD‐related traits (OR: 1.046, 95% CI: 0.764, 1.433 and OR: 1.014, 95% CI: 0.968, 1.062 for imaging‐based and biopsy‐confirmed NAFLD, respectively). MR‐Egger regression revealed a statistically significant intercept, indicative of directional pleiotropy, for all traits. Repeat analyses after exclusion of genes associated with impaired VLDL secretion showed consistent associations between genetically predicted NAFLD and CAD for all traits (i.e., cALT [OR: 1.203, 95% CI: 1.113, 1.300]), imaging‐based (OR: 2.149, 95% CI: 1.276, 3.620) and biopsy‐confirmed NAFLD (OR: 1.113, 95% CI: 1.041, 1.189), which persisted when more stringent biopsy‐confirmed NAFLD criteria were used (OR: 1.154, 95% CI: 1.043, 1.278) or when more stringent MR methods were applied. MR‐Egger regression did not show a statistically significant intercept. Conclusion: The two‐sample MR analyses showed a robust association between genetically predicted NAFLD and CAD after exclusion of genetic variants that are implicated in impaired VLDL secretion.
Aducanumab-Related Amyloid-Related Imaging Abnormalities
Authors: Poul F. Høilund-Carlsen, Thomas J. Werner, Abass Alavi, Mona-Elisabeth Revheim
Journal: Clinical Nuclear Medicine (2022)

Abstract When the FDA granted accelerated approval of Biogen's Alzheimer disease drug, aducanumab (marketed as Aduhelm), it deviated from its mission of guaranteeing drug safety and efficacy because the approval was based exclusively on a perceived dose-dependent reduction in brain amyloid deposits and not upon a proven clinical effect. We believe that the amyloid-PET scans, perceived as showing decreasing amyloid deposits, are an expression of increased cerebral cell death due to aducanumab treatment, so that with time one should instead expect a worsening and not an improvement in the treated patients' condition.
The delivery plan for tackling the covid-19 backlog of elective care falls short
Authors: Jessamy Bagenal
Journal: BMJ (2022)

physician and senior medical editorTreating the more than six million people currently on the elective waiting list in the UK is a gargantuan task.There are no easy solutions, and the list is likely to get longer before it gets shorter. 1 But the backlog is also a direct result of a poor national response to covid-19, coupled with an NHS that was under resourced, underfunded, and understaffed even before the pandemic. 2 The NHS lacked the right balance of hardware (infrastructure, finance, workforce) and software (management knowledge, skills, trust) or any necessary excess capacity to respond to the shock of the pandemic. 3 A plan to tackle the backlog needed to start from this foundational point.Sadly, NHS England and Improvement's recent plan: Delivery plan for tackling the covid-19 backlog of elective care, does not. 4 By any measure, the extent of the backlog is a serious failure.Patients are suffering physically and emotionally, which contributes to poorer health.Confidence and trust in the system are weakened, and the economic consequences are huge for individuals and society.How we respond to the backlog is therefore crucial.Getting it right will provide a "resilience dividend" of improved future care in both good times and bad times. 5The plan acknowledges the scale of the problem, recognises it as an opportunity to transform care, and-importantly-recognises the unequal distribution of waiting times: waiting lists in the most deprived areas have grown by 55% whereas those in the least deprived areas have grown by 36%. 6 But the plan fails to acknowledge the legacy of policies introduced over the past decade.It promises to increase elective activity by 30% by 2024-25, but does not acknowledge that before the pandemic, the waiting list grew from 2.9 million pathways in January 2015 to 4.4 million pathways in December 2019. 7 It would, of course, be politically difficult to make such an admission, but avoiding this means the ambitions of the plan start from the wrong place.
Seamless and early gap healing of osteochondral defects by autologous mosaicplasty combined with bioactive supramolecular nanofiber-enabled gelatin methacryloyl (BSN-GelMA) hydrogel
Authors: Hongwei Wu, Yuna Shang, Wei Sun, Xinyi Ouyang, Wenyan Zhou, Jieji Lu, Shuhui Yang, Wei Wei, Xudong Yao, Xiaozhao Wang, Xianzhu Zhang, Yishan Chen, Qiulin He, Zhimou Yang, Hongwei Ouyang
Journal: Bioactive Materials (2022)

Autologous mosaicplasty is a common approach used to treat osteochondral defects in clinical practice. Gap integration between host and transplanted plugs requires bone tissue reservation and hyaline cartilage regeneration without uneven surface, graft necrosis and sclerosis. However, poor gap integration is a serious concern, which eventually leads to deterioration of joint function. To deal with such complications, this study has developed a strategy to effectively enhance integration of the gap region following mosaicplasty by applying injectable bioactive supramolecular nanofiber-enabled gelatin methacryloyl (GelMA) hydrogel (BSN-GelMA). A rabbit osteochondral defect model demonstrated that BSN-GelMA achieved seamless osteochondral healing in the gap region between plugs of osteochondral defects following mosaicplasty, as early as six weeks. Moreover, the International Cartilage Repair Society score, histology score, glycosaminoglycan content, subchondral bone volume, and collagen II expression were observed to be the highest in the gap region of BSN-GelMA treated group. This improved outcome was due to bio-interactive materials, which acted as tissue fillers to bridge the gap, prevent cartilage degeneration, and promote graft survival and migration of bone marrow mesenchymal stem cells by releasing bioactive supramolecular nanofibers from the GelMA hydrogel. This study provides a powerful and applicable approach to improve gap integration after autologous mosaicplasty. It is also a promising off-the-shelf bioactive material for cell-free in situ tissue regeneration.
Association of Adjuvant Chemotherapy With Overall Survival Among Patients With Locally Advanced Gastric Cancer After Neoadjuvant Chemotherapy
Authors: Jian-Xian Lin, Yi-Hui Tang, Guan-Jie Lin, Yu-Bin Ma, Jacopo Desiderio, Ping Li, Jian-Wei Xie, Jia-Bin Wang, Jun Lu, Qi-Yue Chen, Long-Long Cao, Mi Lin, Ru-Hong Tu, Chao-Hui Zheng, Amilcare Parisi, Mark J. Truty, Chang-Ming Huang
Journal: JAMA Network Open (2022)

Neoadjuvant chemotherapy (NAC) is a standard treatment option for locally advanced gastric cancer (LAGC); however, the indications for adjuvant chemotherapy (AC) in patients with LAGC who received NAC remain controversial.
RETRACTED ARTICLE: Subsequent anti-myeloma therapy after idecabtagene vicleucel treatment in patients with relapsed/refractory multiple myeloma: A single center analysis
Authors: Ricardo D. Parrondo, Keren Sam, Ahsan Rasheed, Victoria Alegria, Taimur Sher, Vivek Roy, Asher Chanan-Khan, Sikander Ailawadhi
Journal: Blood Cancer Journal (2022)
Prevalence and risk factors of birth-related posttraumatic stress among parents: A comparative systematic review and meta-analysis
Authors: Clara-Sophie Heyne, Maria Kazmierczak, Ronnie Souday, Danny Horesh, Mijke Lambregtse-van den Berg, Tobias Weigl, Antje Horsch, Mirjam Oosterman, Pelin Dikmen-Yildiz, Susan Garthus-Niegel
Journal: Clinical Psychology Review (2022)
<i>Helicobacter pylori</i> Modulated Host Immunity in Gastric Cancer Patients With S-1 Adjuvant Chemotherapy
Authors: Yuka Koizumi, Sheny Ahmad, Miyuki Ikeda, Akiko Yashima-Abo, Ginny Espina, Ryo Sugimoto, Tamotsu Sugai, Takeshi Iwaya, Gen Tamura, Keisuke Koeda, Lance A Liotta, Fumiaki Takahashi, Satoshi S Nishizuka
Journal: JNCI Journal of the National Cancer Institute (2022)

Paradoxically, Helicobacter pylori-positive (HP+) advanced gastric cancer patients have a better prognosis than those who are HP-negative (HP-). Immunologic and statistical analyses can be used to verify whether systemic mechanisms modulated by HP are involved in this more favorable outcome.A total of 658 advanced gastric cancer patients who underwent gastrectomy were enrolled. HP infection, mismatch repair, programmed death-ligand 1 (PD-L1) and CD4/CD8 proteins, and microsatellite instability were analyzed. Overall survival (OS) and relapse-free survival (RFS) rates were analyzed after stratifying clinicopathological factors. Cox proportional hazards regression analysis was performed to identify independent prognostic factors.Among 491 patients that were analyzed, 175 (36%) and 316 (64%) patients were HP+ and HP-, respectively. Analysis of RFS indicated an interaction of HP status among the subgroups for S-1 dose (Pinteraction = .049) and PD-L1 (P = .02). HP+ patients in the PD-L1- group had statistically higher 5-year OS and RFS than HP- patients (81% vs 68%; P = .0011; hazard ratio [HR] = 0.48, 95% confidence interval [CI] = 0.303 to 0.751, and 76% vs 63%; P = .001; HR = 0.508, 95% CI = 0.335 to 0.771, respectively). The 5-year OS and RFS was also statistically higher for HP+ compared with HP- patients in the "PD-L1- and S-1-r educed" group (86% vs 46%; P = .001; HR = 0.205, 95% CI = 0.07 to 0.602, and 83% vs 34%; P = .001; HR = 0.190, 95% CI = 0.072 to 0.498, respectively). Thus, HP status was identified as one of the most potentially important independent factors to predict prolonged survival.This retrospective study suggests that an HP-modulated host immune system may contribute to prolonged survival in the absence of immune escape mechanisms of gastric cancer.
An Asia-specific variant of human IgG1 represses colorectal tumorigenesis by shaping the tumor microenvironment
Authors: Bing Yang, Zhen Zhang, Xiangjun Chen, Xu-Yan Wang, Shishang Qin, Liaoqi Du, Changjiang Yang, Liyu Zhu, Wenbo Sun, Yongjie Zhu, Qinwen Zheng, Shidong Zhao, Quan Wang, Long Zhao, Yilin Lin, Jinghe Huang, Fan Wu, Lu Lu, Fei Wang, Wenjie Zheng, Xiao-Hua Zhou, Xiaozhen Zhao, Ziye Wang, Sun Xiao-Lin, Yingjiang Ye, Shan Wang, Zhanguo Li, Hai Qi, Zemin Zhang, Dong-Ming Kuang, Lei Zhang, Zhanlong Shen, Wanli Liu
Journal: Journal of Clinical Investigation (2022)

Emerging studies have focused on ways to treat cancers by modulating T cell activation. However, whether B cell receptor signaling in the tumor microenvironment (TME) can be harnessed for immunotherapy is unclear. Here, we report that an Asia-specific variant of human IgG1 containing a Gly396 to Arg396 substitution (hIgG1-G396R) conferred improved survival of patients with colorectal cancer (CRC). Mice with knockin of the murine functional homolog mIgG2c-G400R recapitulated the alleviated tumorigenesis and progression in murine colon carcinoma models. Immune profiling of the TME revealed broad mobilizations of IgG1+ plasma cells, CD8+ T cells, CD103+ DCs, and active tertiary lymphoid structure formation, suggesting an effective antitumor microenvironment in hIgG1-G396R CRC patients. Mechanistically, this variant potentiated tumor-associated antigen–specific (TAA-specific) plasma cell differentiation and thus antibody production. These elevated TAA-specific IgG2c antibodies in turn efficiently boosted the antibody-dependent tumor cell phagocytosis and TAA presentation to effector CD8+ T cells. Notably, adoptive transfer of TAA-specific class-switched memory B cells harboring this variant exhibited therapeutic efficacy in murine tumor models, indicating their clinical potential. All these results prompted a prospective investigation of hIgG1-G396R in patients with CRC as a biomarker for clinical prognosis and demonstrated that manipulating the functionality of IgG1+ memory B cells in tumors could improve immunotherapy outcomes.
Phylogenomic Analyses of Alismatales Shed Light into Adaptations to Aquatic Environments
Authors: Ling-Yun Chen, Bei Lu, Diego F. Morales-Briones, Michael L. Moody, Fan Liu, Guang-Wan Hu, Chien-Hsun Huang, Jin-Ming Chen, Qing-Feng Wang
Journal: Molecular Biology and Evolution (2022)

Land plants first evolved from freshwater algae, and flowering plants returned to water as early as the Cretaceous and multiple times subsequently. Alismatales is the largest clade of aquatic angiosperms including all marine angiosperms, as well as terrestrial plants. We used Alismatales to explore plant adaptations to aquatic environments by analyzing a data set that included 95 samples (89 Alismatales species) covering four genomes and 91 transcriptomes (59 generated in this study). To provide a basis for investigating adaptations, we assessed phylogenetic conflict and whole-genome duplication (WGD) events in Alismatales. We recovered a relationship for the three main clades in Alismatales as (Tofieldiaceae, Araceae) + core Alismatids. We also found phylogenetic conflict among the three main clades that was best explained by incomplete lineage sorting and introgression. Overall, we identified 18 putative WGD events across Alismatales. One of them occurred at the most recent common ancestor of core Alismatids, and three occurred at seagrass lineages. We also found that lineage and life-form were both important for different evolutionary patterns for the genes related to freshwater and marine adaptation. For example, several light- or ethylene-related genes were lost in the seagrass Zosteraceae, but are present in other seagrasses and freshwater species. Stomata-related genes were lost in both submersed freshwater species and seagrasses. Nicotianamine synthase genes, which are important in iron intake, expanded in both submersed freshwater species and seagrasses. Our results advance the understanding of the adaptation to aquatic environments and WGDs using phylogenomics.
Antisense oligonucleotides ameliorate kidney dysfunction in podocyte-specific APOL1 risk variant mice
Authors: Ya-Wen Yang, Bibek Poudel, Julia Frederick, Poonam Dhillon, Rojesh Shrestha, Ziyuan Ma, Junnan Wu, Koji Okamoto, Jeffrey B. Kopp, Sheri L. Booten, Danielle Gattis, Andrew T. Watt, Matthew Palmer, Mariam Aghajan, Katalin Susztak
Journal: Molecular Therapy (2022)

Coding variants (named G1 and G2) in Apolipoprotein L1 (APOL1) can explain most excess risk of kidney disease observed in African American individuals. It has been proposed that risk variant APOL1 dose, such as increased risk variant APOL1 level serves as a trigger (second hit) for disease development. The goal of this study was to determine whether lowering risk variant APOL1 levels protects from disease development in a podocyte-specific transgenic mouse disease model. We administered antisense oligonucleotides (ASO) targeting APOL1 to podocyte-specific G2APOL1 mice and observed efficient reduction of APOL1 levels. APOL1 ASO1, which more efficiently lowered APOL1 transcript levels, protected mice from albuminuria, glomerulosclerosis, tubulointerstitial fibrosis, and renal failure. Administration of APOL1 ASO1 was effective even for established disease in the NEFTA-rtTA/TRE-G2APOL1 (NEFTA/G2APOL1) mice. We observed a strong correlation between APOL1 transcript level and disease severity. We concluded that APOL1 ASO1 may be an effective therapeutic approach for APOL1-associated glomerular disease. Coding variants (named G1 and G2) in Apolipoprotein L1 (APOL1) can explain most excess risk of kidney disease observed in African American individuals. It has been proposed that risk variant APOL1 dose, such as increased risk variant APOL1 level serves as a trigger (second hit) for disease development. The goal of this study was to determine whether lowering risk variant APOL1 levels protects from disease development in a podocyte-specific transgenic mouse disease model. We administered antisense oligonucleotides (ASO) targeting APOL1 to podocyte-specific G2APOL1 mice and observed efficient reduction of APOL1 levels. APOL1 ASO1, which more efficiently lowered APOL1 transcript levels, protected mice from albuminuria, glomerulosclerosis, tubulointerstitial fibrosis, and renal failure. Administration of APOL1 ASO1 was effective even for established disease in the NEFTA-rtTA/TRE-G2APOL1 (NEFTA/G2APOL1) mice. We observed a strong correlation between APOL1 transcript level and disease severity. We concluded that APOL1 ASO1 may be an effective therapeutic approach for APOL1-associated glomerular disease.
A biomimetic and bioactive scaffold with intelligently pulsatile teriparatide delivery for local and systemic osteoporosis regeneration
Authors: Lingbin Che, Ying Wang, Dongyong Sha, Guangyi Li, Ziheng Wei, Changsheng Liu, Yuan Yuan, Dianwen Song
Journal: Bioactive Materials (2022)

Osteoporosis is one of the most disabling consequences of aging, osteoporotic fractures and higher risk of the subsequent fractures leading to substantial disability and deaths, indicating both local fractures healing and the early anti-osteoporosis therapy are of great significance. Teriparatide is strong bone formation promoter effective in treating osteoporosis, while side effects limit clinical applications. Traditional drug delivery is lack of sensitive and short-term release, finding a new non-invasive and easily controllable drug delivery to not only repair the local fractures but also improve total bone mass has remained a great challenge. Thus, bioinspired by the natural bone components, we develop appropriate interactions between inorganic biological scaffolds and organic drug molecules, achieving both loaded with the teriparatide in the scaffold and capable of releasing on demand. Herein, biomimetic bone microstructure of mesoporous bioglass, a near-infrared ray triggered switch, thermosensitive liposomes based on a valve, and polydopamine coated as a heater is developed rationally for osteoporotic bone regeneration. Teriparatide is pulsatile released from intelligent delivery, not only rejuvenating osteoporotic bone defect, but also presenting strong systemic anti-osteoporosis therapy. This biomimetic bone carrying novel drug delivery platform is well worth expecting to be a new promising strategy and clinically commercialized to help patients survive from the osteoporotic fracture.
Single-cell and spatial RNA sequencing identify perturbators of microglial functions with aging
Authors: Yifei Dong, Rajiv W. Jain, Brian M. Lozinski, Charlotte D’Mello, Frank Visser, Samira Ghorbani, Stephanie Zandee, Dennis I. Brown, Alexandre Prat, Mengzhou Xue, V. Wee Yong
Journal: Nature Aging (2022)