bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of physical activity on anthropometric characteristics in school-age children: A review study
Authors: Lilić Ana , Petković Emilija , Karišik Siniša , Bjelojević Ljiljana , Gardašević Novica , Joksimović Marko
Published: July 2021

Background. Today, it is very speculative  to talk about the percentage of obese children in the world because these figures change significantly from day to day, and there are even significant differences between respondents in the same country, according to geographical area and place of residence. A constant decline in the level of physical activity of children on a global level can be reported from the age when they start school. Energy intake of food is largely from energy consumption, which leads to an increase in body weight and obesity. Factors of overweight and obesity are associated with a sensitive comparison of health: a significantly increased risk of diabetes, disorders of the locomotor system, and increased social and psychological rights.

Methods and results. During the systematization of the research on the topic, the aim of the paper was to determine whether the influence of physical activity on anthropometric parameters in school-age children is reviewed by previous research. Nineteen types of studies were collected. The following electronic databases were used to search the literature: MEDLINE, SCOPUS, Web of Science SPORTS DISCUS in the period from 2004 to 2016. The respondents included in the research were school-age children.

Conclusion. The positive impact of various physical activity programs is aimed at reducing the parameters of anthropometric characteristics and obesity prevention.

Keywords: physical activity, school program, morphology, anthropomeric data, exercises.
PERBEDAAN EFEKTIVITAS PROMOSI KESEHATAN MENGGUNAKAN MEDIA FILM DENGAN DEMONSTRASI TERHADAP PENGETAHUAN DAN SIKAP PUS TENTANG PEMERIKSAAN IVA
Authors: Handini Haspita Rizki Syurya
Published: July 2021

Cervical cancer is one of the leading causes of death and health problems in women. Cervical cancer can be prevented by early detection using the IVA method. Until 2018, only 7,34% of women underwent IVA examinations. IVA examination is not widely known by the public, so an effort is needed to increase the knowledge and attitudes of mothers about IVA examinations by providing health promotion with the right methods and media. The research objective was to determine the differences in the effectiveness of health promotion with film and demonstration media on the knowledge and attitudes of mothers about IVA examination. This type of research is a quasi-experimental design with a non-randomized two group pretest posttest design. The population was all women in the working area of ​​Lubuk Buaya Health Center. There was a significant difference in the knowledge of mothers before and after being given health promotion with film and demonstration media (p <0,05), however, there was no significant difference in the attitudes of mothers before and after being given health promotion using film and demonstration media (p>0,05). It can be concluded that demonstrations are more effective than films in increasing maternal knowledge, whereas maternal attitudes, demonstrations and films are equally influential. It is hoped that midwives can provide health promotion by means of demonstration media because it is more effective in increasing knowledge and attitudes about IVA examinations.
GAMBARAN KEPATUHAN DIET PADA ANGGOTA PROLANIS SELAMA PANDEMI COVID-19 DI WILAYAH KERJA PUSKESMAS BOJONG 2
Authors: Umam Moh. Khotibul , Imaningtias Windi , Listianingrum Nurul Hidayati
Published: July 2021

Non-communicable diseases (NCDs) are the leading causes of death and are responsible for the highest mortality rates in the world and in Indonesia. One of the programs for controlling NCDs especially hypertension and Diabetes at the Public Health Center (PHC) is Prolanis. One of the Prolanis programs is the monitoring of dietary adherence among Prolanis members. A descriptive research design was used as research method. The samples of this study were 34 Prolanis members in Sumurjomblang Bogo Village, the working area of Puskesmas Bojong 2. The results showed that the majority of Prolanis members in Sumurjomblang Bogo did not compliant the right schedule of diet (80%), the right type of diet (60%), and the right number of diet (60 %) for diabetes mellitus and hypertension. This may be due to lack of monitoring from health workers. Therefore, the results of this study are expected for an online diet counseling and monitoring program involving families of prolanis members during covid-19 pandemic.
HUBUNGAN KARAKTERISTIK AKSEPTOR KB SUKU MADURA DENGAN PEMILIHAN JENIS KONTRASEPSI DI PUSKESMAS OMBEN KABUPATEN SAMPANG
Authors: Rizaldi Nanda
Published: July 2021

The amount of people in Indonesia always increase over and over each year so the government implement a program called KB or Family Planning which aims to control the birth rate of the country. In implementing KB program, there are many debatable pro-cons in people, one of them is Madurese people who assume that one of the contraceptives are considered inadequate to be used from a religious and cultural perspective. This study aims to find out the relationship between a Madurese family planning acceptor and the choice of contraception. The research method is analytic observational with Cross Sectional Study. The method of sampling is probability type, used the simple random sampling. This study used questionnaire to collect the data and chi-square test to analyse the data. The result of the study showed that the respondents who choose short-term contraception type is 95 people and the long-term contraception is 15 people. The result of the data analysis showed that there is a relationship of age (0,043), number of children (0,006), economical status (0,005), and socio-cultural (0,002) in choosing the contraception type. Meanwhile, the education (0,923) has no relation in the choose of contraception type.. It is expected that the prospective family planning acceptors can increase their knowledge of KB (Family Planning) and for the health service workers can increase the health promotion of KB so people can broaden their knowledge of KB.
ANALISIS BIPLOT ATAS KINERJA PEMERINTAH DALAM PENANGANAN STUNTING DI INDONESIA
Authors: Raden Agung Lestanto Notosoediro , Pramaputri Dinda Dea
Published: July 2021

Prevalensi stunting di Indonesia, meskipun telah menunjukan penurunan dalam delapan tahun terakhir, masih relatif tinggi dibandingkan dengan negara lain di Kawasan. Penelitian ini bertujuan untuk memetakan provinsi di Indonesia berdasarkan indikator sosial ekonomi serta indikator kinerja terkait dengan intervensi stunting untuk kemudian dilakukan identifikasi perbaikan agar kinerja penurunan stunting pada level provinsi dapat ditingkatkan. Berdasarkan analisis biplot diperoleh bahwa prevalensi stunting memiliki korelasi positif dengan tingkat kemiskinan dan berkorelasi negatif dengan IPM. Hubungan antar peubah utilitas fasilitas kesehatan untuk kelahiran, ASI eksklusif, serta asupan makanan/gizi untuk bayi usia 6 s.d. 24 bulan menunjukan adanya korelasi positif. Peubah cakupan imunisasi dasar lengkap memiliki korelasi positif dengan peubah PAUD. Selanjutnya, hasil pengelompokan provinsi menunjukkan bahwa terdapat delapan kelompok provinsi dengan dengan kelompok yang memiliki anggota terbanyak adalah kelompok yang memiliki karakteristik prevalensi stunting yang tinggi dan indikator yang rendah untuk utilitas fasilitas kesehatan untuk kelahiran, ASI eksklusif, serta asupan makanan/gizi untuk bayi usia 6 s.d. 24 bulan.
Mesangiogenic Progenitor Cells Are Tissue Specific and Cannot Be Isolated From Adipose Tissue or Umbilical Cord Blood
Authors: Barachini Serena , Montali Marina , Panvini Francesca M. , Carnicelli Vittoria , Gatti Gian Luca , Piolanti Nicola , Bonicoli Enrico , Scaglione Michelangelo , Buda Gabriele , Parchi Paolo D.
Published: July 2021

Mesangiogenic progenitor cells (MPCs) have been isolated from human bone marrow (BM) mononuclear cells. They attracted particular attention for the ability to differentiate into exponentially growing mesenchymal stromal cells while retaining endothelial differentiative potential. MPC power to couple mesengenesis and angiogenesis highlights their tissue regenerative potential and clinical value, with particular reference to musculoskeletal tissues regeneration. BM and adipose tissue represent the most promising adult multipotent cell sources for bone and cartilage repair, although discussion is still open on their respective profitability. Culture determinants, as well as tissues of origin, appeared to strongly affect the regenerative potential of cell preparations, making reliable methods for cell isolation and growth a prerequisite to obtain cell-based medicinal products. Our group had established a definite consistent protocol for MPC culture, and here, we present data showing MPCs to be tissue specific.
Adipocytes and Stromal Cells Regulate Brown Adipogenesis Through Secretory Factors During the Postnatal White-to-Brown Conversion of Adipose Tissue in Syrian Hamsters
Authors: Mae Junnosuke , Nagaya Kazuki , Okamatsu-Ogura Yuko , Tsubota Ayumi , Matsuoka Shinya , Nio-Kobayashi Junko , Kimura Kazuhiro
Published: July 2021

Brown adipose tissue (BAT) is a specialized tissue that regulates non-shivering thermogenesis. In Syrian hamsters, interscapular adipose tissue is composed primarily of white adipocytes at birth, which is converted to BAT through the proliferation and differentiation of brown adipocyte progenitors and the simultaneous disappearance of white adipocytes. In this study, we investigated the regulatory mechanism of brown adipogenesis during postnatal BAT formation in hamsters. Interscapular adipose tissue of a 10-day-old hamster, which primarily consists of brown adipocyte progenitors and white adipocytes, was digested with collagenase and fractioned into stromal–vascular (SV) cells and white adipocytes. SV cells spontaneously differentiated into brown adipocytes that contained multilocular lipid droplets and expressed uncoupling protein 1 (Ucp1), a marker of brown adipocytes, without treatment of adipogenic cocktail such as dexamethasone and insulin. The spontaneous differentiation of SV cells was suppressed by co-culture with adipocytes or by the addition of white adipocyte-conditioned medium. Conversely, the addition of SV cell-conditioned medium increased the expression of Ucp1. These results indicate that adipocytes secrete factors that suppress brown adipogenesis, whereas SV cells secrete factors that promote brown adipogenesis. Transcriptome analysis was conducted; however, no candidate suppressing factors secreted from adipocytes were identified. In contrast, 19 genes that encode secretory factors, including bone morphogenetic protein (BMP) family members, BMP3B, BMP5, and BMP7, were highly expressed in SV cells compared with adipocytes. Furthermore, the SMAD and MAPK signaling pathways, which represent the major BMP signaling pathways, were activated in SV cells, suggesting that BMPs secreted from SV cells induce brown adipogenesis in an autocrine manner through the SMAD/MAPK signaling pathways. Treatment of 5-day-old hamsters with type I BMP receptor inhibitor, LDN-193189, for 5 days reduced p38 MAPK phosphorylation and drastically suppressed BAT formation of interscapular adipose tissue. In conclusion, adipocytes and stromal cells regulate brown adipogenesis through secretory factors during the postnatal white-to-brown conversion of adipose tissue in Syrian hamsters.
Single-Molecule Techniques to Study Chromatin
Authors: Chanou Anna , Hamperl Stephan
Published: July 2021

Besides the basic organization in nucleosome core particles (NCPs), eukaryotic chromatin is further packed through interactions with numerous protein complexes including transcription factors, chromatin remodeling and modifying enzymes. This nucleoprotein complex provides the template for many important biological processes, such as DNA replication, transcription, and DNA repair. Thus, to understand the molecular basis of these DNA transactions, it is critical to define individual changes of the chromatin structure at precise genomic regions where these machineries assemble and drive biological reactions. Single-molecule approaches provide the only possible solution to overcome the heterogenous nature of chromatin and monitor the behavior of individual chromatin transactions in real-time. In this review, we will give an overview of currently available single-molecule methods to obtain mechanistic insights into nucleosome positioning, histone modifications and DNA replication and transcription analysis—previously unattainable with population-based assays.
Making the Invisible Stratigraphy Visible: A Grid-Based, Multi-Proxy Geoarchaeological Study of Umhlatuzana Rockshelter, South Africa
Authors: Reidsma Femke H. , Sifogeorgaki Irini , Dinckal Ada , Huisman Hans , Sier Mark J. , van Os Bertil , Dusseldorp Gerrit L.
Published: July 2021

Umhlatuzana rockshelter is an archaeological site with an occupational record covering the Middle Stone Age, Later Stone Age, and Iron Age. The presence of both Middle and Later Stone Age assemblages makes Umhlatuzana the ideal location for the study of the MSA–LSA transition (20–40 ka) in southern Africa. This transitional period is characterized by important modifications in stone tool technology, from prepared core technology to a toolkit based on microlith production. These changes are argued to have occurred in response to changes in climate and environment leading up to the Last Glacial Maximum. The deposits bearing the transitional assemblages at Umhlatuzana rockshelter appear homogeneous with no visible stratigraphic boundaries. This study integrates geoarchaeological techniques in order to explore fine-resolution geochemical differentiations of the sediments that are macroscopically invisible, and that will provide insight into (post-)depositional processes over time. Samples were systematically retrieved from the western profile of the site following a grid-based sampling strategy and analyzed for pH, elemental composition (XRF), and Magnetic Susceptibility. Additionally, the results were integrated with preliminary micromorphological observations. Our study reveals a steady, gradual change in the geochemistry of the deposits throughout the Pleistocene, related to a combination of environmental change and occupation intensity. We suggest that the part of the sequence reported to bear Middle to Later Stone Age transitional industries is characterized by wetter environmental conditions compared to the underlying deposits. Additionally, we support results from previous studies that excluded large scale post-depositional movement of the sedimentary sequence. Our study offers a successful multi-proxy approach to systematically sample and study archaeological deposits at the macro and micro scale, integrating a variety of geoarchaeological techniques. The approach provides insight into the depositional and post-depositional history of the site, and allows for questions of stratigraphic integrity, anthropogenic input, preservation, and environmental change to be addressed.
Persistence of Underrepresented Minorities in STEM Fields: Are Summer Bridge Programs Sufficient?
Authors: Ghazzawi Dina , Pattison Donna , Horn Catherine
Published: July 2021

Disparities in undergraduate STEM degree completion across different racial/ethnic groups have been a topic of increasing national concern. This study investigates the long-term outcomes of a STEM intervention program designed to increase the academic preparation, achievement and persistence of under-represented minority students.In particular, this study examines the extent to which participation in a STEM intervention program can impact the long-term persistence and graduation of first-time in college under-represented minority students. Using discrete-time competing risks analysis, results demonstrated that participants of the intervention program had a lower probability of drop out and higher probability of persisting in a STEM field of study compared to non-participants of the program. Additionally, descriptive results demonstrated that participants of the STEM intervention program had higher rates of graduation in any field compared to non-participants of the program, while program participation was not a significant predictor of six-year graduation. Findings highlight the importance of early academic preparation in Calculus and total credit accumulation to student success outcomes of URM students enrolled in STEM fields. Recommendations from this study focus on early intervention efforts, particularly in the areas of mathematics, that ensure URM students are adequately prepared with the skills needed to succeed in a STEM field of study.
Comparison of N2O Emissions From Cold Waterlogged and Normal Paddy Fields
Authors: Xu Xiangyu , Zhang Minmin , Xiong Yousheng , Shaaban Muhammad , Yuan Jiafu , Hu Ronggui
Published: July 2021

Paddy fields are major sources of atmospheric N2O. Soil temperature and moisture strongly affect N2O emissions from rice fields. However, N2O emissions from cold-waterlogged paddy fields (CW), an important kind of paddy soil in China, are not well studied so far. It is unclear whether the N2O emissions from cold-waterlogged paddy fields are the same as normal paddy fields (NW). We investigated the N2O emission characteristics from the CW and NW paddy fields under with (R1) and without (R0) rice in Tuku Village, Baisha Town, Yangxin County (YX site, monitoring in 2013) and Huandiqiao Town, Daye City (DY site, monitoring in 2014); compared the difference and influencing factors between the CW and NW paddy fields at two sites in South China. The results showed that the N2O emissions from NWR0 were 13.4 times higher than from CWR0, and from NWR1 were 10.3 times higher than from CWR1 in the YX site. The N2O emissions from NWR0 were 2.4 times higher than from CWR0, and from NWR1 were 17.3 times higher than from CWR1 in the DY site. The structural equation models (SEMs) showed that the N2O emissions are mainly driven by rice planting and soil moisture in the NW fields at the annual scale, while soil temperature in the CW fields. Overall, N2O emissions from cold waterlogged paddy fields are significantly lower than those of normal paddy fields due to the low temperature and higher water content; however, there are dinitrogen emissions from cold waterlogged paddy fields denitrification should be further examined.
Restoration of Natural Forests After Severe Wind Disturbance in a Cold, Snowy Region With a Deer Population: Implications From 15 Years of Field Experiments
Authors: Morimoto Junko , Sugiura Mio , Morimoto Miho , Nakamura Futoshi
Published: July 2021

Questions have been raised about the application of conventional post-windthrow forest practices such as salvage logging, site preparation, and afforestation in response to the increase in wind disturbance caused by climate change. In particular, it is necessary to identify effective forest management practices that consider the pressure from deer browsing in forests in cold, snowy regions because the population of ungulates is expected to increase. The impacts of legacy destruction, i.e., the destruction of advance regeneration, microsites, and soil structure, caused by conventional post-windthrow practices have rarely been assessed separately from the impacts of subsequent deer browsing on forest regeneration or evaluated based on sufficiently long monitoring periods to assess vegetation succession. This lack of studies is one reason that alternative forest management practices to salvaging and planting have not been proposed. We conducted a field experiment at a large-scale windthrow site with a deer population to (1) assess the impact of legacy destruction and deer browsing on vegetation biomass and species composition after 15 years and (2) identify the effects of legacy retention. The study design allowed us to distinguish between and measure the impact of legacy destruction and that of subsequent deer browsing during a 15-year period. The results revealed the following: (1) Salvage logging and site preparation suppressed the development of biomass of shrub and tree layers in forested areas where harvest residues were piled up and shifted the plant communities in these areas to herbaceous plant communities. (2) Subsequent deer browsing suppressed the development of the biomass of shrub and tree layers throughout the forested site and shifted herbaceous communities to ruderal communities dominated by alien species; and 3. Compared with salvaging and planting, legacy retention enabled the windthrow sites to more quickly develop into a stand with characteristics similar to that of a mature, natural forest. Forest management practices that consider the presence of deer are necessary. We propose a policy shift from planting trees after salvaging to leaving downed trees to regenerate natural forests, unless there is concern about insect damage to the remaining forestry land in the vicinity.
Prediction of a Competing Endogenous RNA Co-expression Network by Comprehensive Methods in Systemic Sclerosis-Related Interstitial Lung Disease
Authors: Yan Yue-Mei , Zheng Ji-Na , Wu Li-Wei , Rao Qian-Wen , Yang Qiao-Rong , Gao Di , Wang Qiang
Published: July 2021

Systemic sclerosis (SSc) is an immune-mediated connective tissue disease characterized by fibrosis of multi-organs, and SSc-related interstitial lung disease (SSc-ILD) is a leading cause of morbidity and mortality. To explore molecular biological mechanisms of SSc-ILD, we constructed a competing endogenous RNA (ceRNA) network for prediction. Expression profiling data were obtained from the Gene Expression Omnibus (GEO) database, and differential expressed mRNAs and miRNAs analysis was further conducted between normal lung tissue and SSc lung tissue. Also, the interactions of miRNA–lncRNA, miRNA–mRNA, and lncRNA–mRNA were predicted by online databases including starBase, LncBase, miRTarBase, and LncACTdb. The ceRNA network containing 11 lncRNAs, 7 miRNAs, and 20 mRNAs were constructed. Based on hub genes and miRNAs identified by weighted correlation network analysis (WGCNA) method, three core sub-networks—SNHG16, LIN01128, RP11-834C11.4(LINC02381)/hsa-let-7f-5p/IL6, LINC01128/has-miR-21-5p/PTX3, and LINC00665/hsa-miR-155-5p/PLS1—were obtained. Combined with previous studies and enrichment analyses, the lncRNA-mediated network affected LPS-induced inflammatory and immune processes, fibrosis development, and tumor microenvironment variations. The ceRNA network, especially three core sub-networks, may be served as early biomarkers and potential targets for SSc, which also provides further insights into the occurrence, progression, and accurate treatment of SSc at the molecular level.
DysPIA: A Novel Dysregulated Pathway Identification Analysis Method
Authors: Wang Limei , Xie Weixin , Li Kongning , Wang Zhenzhen , Li Xia , Feng Weixing , Li Jin
Published: July 2021

Differential co-expression-based pathway analysis is still limited and not widely used. In most current methods, the pathways were considered as gene sets, but the gene regulation relationships were not considered, and the computational speed was slow. In this article, we proposed a novel Dysregulated Pathway Identification Analysis (DysPIA) method to overcome these shortcomings. We adopted the idea of Correlation by Individual Level Product into analysis and performed a fast enrichment analysis. We constructed a combined gene-pair background which was much more sufficient than the background used in Edge Set Enrichment Analysis. In simulation study, DysPIA was able to identify the causal pathways with high AUC (0.9584 to 0.9896). In p53 mutation data, DysPIA obtained better performance than other methods. It obtained more potential dysregulated pathways that could be literature verified, and it ran much faster (∼1,700–8,000 times faster than other methods when 10,000 permutations). DysPIA was also applied to breast cancer relapse dataset and breast cancer subtype dataset. The results show that DysPIA is effective and has a great biological significance. R packages “DysPIA” and “DysPIAData” are constructed and freely available on R CRAN (https://cran.r-project.org/web/packages/DysPIA/index.htmlandhttps://cran.r-project.org/web/packages/DysPIAData/index.html), and on GitHub (https://github.com/lemonwang2020).
From Science to Success? Targeting Tyrosine Kinase 2 in Spondyloarthritis and Related Chronic Inflammatory Diseases
Authors: Hromadová Dominika , Elewaut Dirk , Inman Robert D. , Strobl Birgit , Gracey Eric
Published: July 2021

Spondyloarthritis (SpA) is a family of inflammatory arthritic diseases, which includes the prototypes of psoriatic arthritis and ankylosing spondylitis. SpA is commonly associated with systemic inflammatory diseases, such as psoriasis and inflammatory bowel disease. Immunological studies, murine models and the genetics of SpA all indicate a pathogenic role for the IL-23/IL-17 axis. Therapeutics targeting the IL-23/IL-17 pathway are successful at providing symptomatic relief, but may not provide complete protection against progression of arthritis. Thus there is still tremendous interest in the discovery of novel therapeutic targets for SpA. Tyrosine kinase 2 (TYK2) is a member of the Janus kinases, which mediate intracellular signaling of cytokines via signal transducer and activator of transcription (STAT) activation. TYK2 plays a crucial role in mediating IL-23 receptor signaling and STAT3 activation. A plethora of natural mutations in and around TYK2 have provided a wealth of data to associate this kinase with autoimmune/autoinflammatory diseases in humans. Induced and natural mutations in murine Tyk2 largely support human data; however, key inter-species differences exist, which means extrapolation of data from murine models to humans needs to be done with caution. Despite these reservations, novel selective TYK2 inhibitors are now proving successful in advanced clinical trials of inflammatory diseases. In this review, we will discuss TYK2 from basic biology to therapeutic targeting, with an emphasis on studies in SpA. Seminal studies uncovering the basic science of TYK2 have provided sound foundations for targeting it in SpA and related inflammatory diseases. TYK2 inhibitors may well be the next blockbuster therapeutic for SpA.
Immune-Related Nine-MicroRNA Signature for Predicting the Prognosis of Gastric Cancer
Authors: Xu Jingxuan , Wen Jian , Li Shuangquan , Shen Xian , You Tao , Huang Yingpeng , Xu Chongyong , Zhao Yaping
Published: July 2021

Recent findings have demonstrated the superiority and utility of microRNAs (miRNAs) as new biomarkers for cancer diagnosis, therapy, and prognosis. In this study, to explore the prognostic value of immune-related miRNAs in gastric cancer (GC), we analyzed the miRNA-expression profiles of 389 patients with GC, using data deposited in The Cancer Genome Atlas database. Using a forward- and backward-variable selection and multivariate Cox regression analyses model, we identified a nine-miRNA signature (the “ImmiRSig,” consisting of miR-125b-5p, miR-99a-3p, miR-145-3p, miR-328-3p, miR-133a-5p, miR-1292-5p, miR-675-3p, miR-92b-5p, and miR-942-3p) in the training cohort that enabled the division of patients into high- and low-risk groups with significantly different survival rates. The ImmiRSig was successfully validated with an independent test cohort of 193 GC patients. Univariate and multivariate Cox regression analyses indicated that the ImmiRSig would serve as an independent prognostic factor after adjusting for other clinical covariates. Pending further prospective validation, the identified ImmiRSig appears to have significant clinical importance in terms of improving outcome predictions and guiding personalized treatment for patients with GC. Finally, significant associations between the ImmiRSig and the half-maximal inhibitory concentrations of chemotherapeutic agents were observed, suggesting that ImmiRSig may predict the clinical efficacy of chemotherapy.
Bispecific Antibody Armed Metabolically Enhanced Headless CAR T Cells
Authors: Thakur Archana , Scholler John , Kubicka Ewa , Bliemeister Edwin T. , Schalk Dana L. , June Carl H. , Lum Lawrence G.
Published: July 2021

Adoptive T cell therapies for solid tumors is challenging. We generated metabolically enhanced co-activated-T cells by transducing intracellular co-stimulatory (41BB, ICOS or ICOS-27) and CD3ζ T cell receptor signaling domains followed by arming with bispecific antibodies (BiAbs) to produce armed “Headless CAR T cells” (hCART). Various hCART armed with BiAb directed at CD3ϵ and various tumor associated antigens were tested for: 1) specific cytotoxicity against solid tumors targets; 2) repeated and dual sequential cytotoxicity; 3) survival and cytotoxicity under in vitro hypoxic condition; and 4) cytokine secretion. The 41BBζ transduced hCART (hCART41BBζ) armed with HER2 BiAb (HER2 hCART41BBζ) or armed with EGFR BiAb (EGFR hCART41BBζ) killed multiple tumor lines significantly better than control T cells and secreted Th1 cytokines/chemokines upon tumor engagement at effector to target ratio (E:T) of 2:1 or 1:1. HER2 hCART serially killed tumor targets up to 14 days. Sequential targeting of EGFR or HER2 positive tumors with HER2 hCART41BBζ followed by EGFR hCART41BBζ showed significantly increased cytotoxicity compared single antigen targeting and continue to kill under in vitro hypoxic conditions. In summary, metabolically enhanced headless CAR T cells are effective serial killers of tumor targets, secrete cytokines and chemokines, and continue to kill under in vitro hypoxic condition.
Efficacy and Safety of Axicabtagene Ciloleucel and Tisagenlecleucel Administration in Lymphoma Patients With Secondary CNS Involvement: A Systematic Review
Authors: Wu XiaoQin , Zhang XinYue , Xun RenDe , Liu MengSi , Sun Zhen , Huang JianChao
Published: July 2021

Background

The efficacy and safety of chimeric antigen receptor T (CAR-T) cell therapy in the treatment of non-Hodgkin’s lymphoma has already been demonstrated. However, patients with a history of/active secondary central nervous system (CNS) lymphoma were excluded from the licensing trials conducted on two widely used CAR-T cell products, Axicabtagene ciloleucel (Axi-cel) and Tisagenlecleucel (Tisa-cel). Hence, the objective of the present review was to assess whether secondary CNS lymphoma patients would derive a benefit from Axi-cel or Tisa-cel therapy, while maintaining controllable safety.

Method

Two reviewers searched PubMed, Embase, Web of Science, and Cochrane library independently in order to identify all records associated with Axi-cel and Tisa-cel published prior to February 15, 2021. Studies that included secondary CNS lymphoma patients treated with Axi-cel and Tisa-cel and reported or could be inferred efficacy and safety endpoints of secondary CNS lymphoma patients were included. A tool designed specifically to evaluate the risk of bias in case series and reports and the ROBINS-I tool applied for cohort studies were used.

Results

Ten studies involving forty-four patients were included. Of these, seven were case reports or series. The other three reports were cohort studies involving twenty-five patients. Current evidence indicates that secondary CNS lymphoma patients could achieve long-term remission following Axi-cel and Tisa-cel treatment. Compared with the non-CNS cohort, however, progression-free survival and overall survival tended to be shorter. This was possibly due to the relatively small size of the CNS cohort. The incidence and grades of adverse effects in secondary CNS lymphoma patients resembled those in the non-CNS cohort. No incidences of CAR-T cell-related deaths were reported. Nevertheless, the small sample size introduced a high risk of bias and prevented the identification of specific patients who could benefit more from CAR-T cell therapy.

Conclusion

Secondary CNS lymphoma patients could seem to benefit from both Axi-cel and Tisa-cel treatment, with controllable risks. Thus, CAR-T cell therapy has potential as a candidate treatment for lymphoma patients with CNS involvement. Further prospective studies with larger samples and longer follow-up periods are warranted and recommended.
Lectin Pathway Mediates Complement Activation by SARS-CoV-2 Proteins
Authors: Ali Youssif M. , Ferrari Matteo , Lynch Nicholas J. , Yaseen Sadam , Dudler Thomas , Gragerov Sasha , Demopulos Gregory , Heeney Jonathan L. , Schwaeble Wilhelm J.
Published: July 2021

Early and persistent activation of complement is considered to play a key role in the pathogenesis of COVID-19. Complement activation products orchestrate a proinflammatory environment that might be critical for the induction and maintenance of a severe inflammatory response to SARS-CoV-2 by recruiting cells of the cellular immune system to the sites of infection and shifting their state of activation towards an inflammatory phenotype. It precedes pathophysiological milestone events like the cytokine storm, progressive endothelial injury triggering microangiopathy, and further complement activation, and causes an acute respiratory distress syndrome (ARDS). To date, the application of antiviral drugs and corticosteroids have shown efficacy in the early stages of SARS-CoV-2 infection, but failed to ameliorate disease severity in patients who progressed to severe COVID-19 pathology. This report demonstrates that lectin pathway (LP) recognition molecules of the complement system, such as MBL, FCN-2 and CL-11, bind to SARS-CoV-2 S- and N-proteins, with subsequent activation of LP-mediated C3b and C4b deposition. In addition, our results confirm and underline that the N-protein of SARS-CoV-2 binds directly to the LP- effector enzyme MASP-2 and activates complement. Inhibition of the LP using an inhibitory monoclonal antibody against MASP-2 effectively blocks LP-mediated complement activation. FACS analyses using transfected HEK-293 cells expressing SARS-CoV-2 S protein confirm a robust LP-dependent C3b deposition on the cell surface which is inhibited by the MASP-2 inhibitory antibody. In light of our present results, and the encouraging performance of our clinical candidate MASP-2 inhibitor Narsoplimab in recently published clinical trials, we suggest that the targeting of MASP-2 provides an unsurpassed window of therapeutic efficacy for the treatment of severe COVID-19.
Predation Cues Lead to Reduced Foraging of Invasive Siganus rivulatus in the Mediterranean
Authors: Shapiro Goldberg Daphna , Rilov Gil , Villéger Sébastien , Belmaker Jonathan
Published: July 2021

Invasive species are one of many anthropogenic challenges to maintaining a healthy marine ecosystem. Two rabbitfish species (Siganus rivulatusandSiganus luridus) are among the more successful migrants from the Red Sea to the Mediterranean, where their intense foraging has caused damage to the algae community, thus reducing primary production and habitat complexity, and impacting nurseries for early life stages. Anecdotal evidence suggests that the impact of rabbitfish on algae is lower in Marine Protected Areas (MPAs) although rabbitfish densities are similar in protected and fished areas. One explanation could be that fear of predators, more often present inside MPAs and an important component of a healthy marine ecosystem, reduces the ecological impacts of rabbitfish. This research aimed to test if such fear effects do occur in rabbitfish. Using controlled mesocosm experiments, we testedS. rivulatusreactions to two chemical predation cues: chemical alarm cues released from a recently killed conspecific fish, and water-borne cues from a tank with a live grouper predator,Epinephelus marginatus.We found that rabbitfish significantly reduce their overall food consumption as well as their bites per minute when exposed to the alarm cue, but not when exposed to the grouper water cue. These results support the idea that MPAs, which effectively increase the density of large piscivores and hence predation, can mitigate the impact of invasive herbivorous species. If the mesocosm results can scale up to natural systems, predation cues may be artificially introduced to other target areas in order to reduce rabbitfish grazing outside reserves. Thus, this study provides information that can be used to manage the ecological impacts caused by invasive rabbitfish, both inside and outside of marine reserves.
Strain Effects on the Diffusion Properties of Near-Surface Self-Interstitial Atoms and Adatoms in Tungsten
Authors: Sun Bochuan , Maroudas Dimitrios , Wirth Brian D. , Martínez Enrique
Published: July 2021

Tungsten (W) is a candidate for the plasma-facing components and divertor in future fusion applications. The material will be subject to a large particle influx (mainly helium and hydrogenic species) that will form bubbles. As bubbles grow, they compress the material, adding to thermal stresses, and eject self-interstitial atoms (SIAs—isolated or in clusters) to release internal pressure. These SIAs diffuse towards the surface in large stress/strain fields and on the surface are thought to act as precursors for nanotendril formation (also known as fuzz) that develops on the material surface modifying its morphology. In this work we analyze the effect of strain on the diffusion properties of both SIAs and adatoms. Relying on atomistic simulations, we compute the average time that a SIA created in the center of a tungsten slab takes to reach a (110) surface for different strains and temperatures. This time relates to the SIA diffusivity and allows to compute the activation energy and dipole tensor including surface effects. We observe a large strain effect that significantly modifies the propensity for SIAs to reach the surface and, hence, to cluster to form dislocation loops in the bulk crystal. Strain also alters the diffusivity of the adatom although to a lesser extent. Finally, we report on the resulting surface roughness evolution and its dependence on strain.
Upregulation of FGD6 Predicts Poor Prognosis in Gastric Cancer
Authors: Zeng Jianmin , Li Man , Shi Huasheng , Guo Jianhui
Published: July 2021

Background: The aim of this study was to investigate the prognostic significance of faciogenital dysplasia 6 (FGD6) in gastric cancer (GC).

Methods: The data of GC patients from The Cancer Genome Atlas (TCGA) database were used for the primary study. Then, our data were validated by the GEO database and RuiJin cohort. The relationship between the FGD6 level and various clinicopathological features was analyzed by logistic regression and univariate Cox regression. Multivariate Cox regression analysis was used to evaluate whether FGD6 was an independent prognostic factor for survival of patients with GC. The relationship between FGD6 and overall survival time was explored by the Kaplan–Meier method. In addition, gene set enrichment analysis (GSEA) was performed to investigate the possible biological processes of FGD6.

Results: The FGD6 level was significantly overexpressed in GC tissues, compared with adjacent normal tissues. The high expression of FGD6 was related to a high histological grade, stage, and T classification and poor prognosis of GC. Multivariate Cox regression analysis showed that FGD6 was an independent prognostic factor for survival of patients with GC. GSEA identified that the high expression of FGD6 was mainly enriched in regulation of actin cytoskeleton.

Conclusion: FGD6 may be a prognostic biomarker for predicting the outcome of patients with GC.
Association of HIV-1 Infection and Antiretroviral Therapy With Type 2 Diabetes in the Hispanic Population of the Rio Grande Valley, Texas, USA
Authors: Lopez-Alvarenga Juan Carlos , Martinez Dora A. , Diaz-Badillo Alvaro , Morales Liza D. , Arya Rector , Jenkinson Christopher P. , Curran Joanne E. , Lehman Donna M. , Blangero John , Duggirala Ravindranath , Mummidi Srinivas , Martinez Ruben D.
Published: July 2021

The Rio Grande Valley (RGV) in South Texas has one of the highest prevalence of obesity and type 2 diabetes (T2D) in the United States (US). We report for the first time the T2D prevalence in persons with HIV (PWH) in the RGV and the interrelationship between T2D, cardiometabolic risk factors, HIV-related indices, and antiretroviral therapies (ART). The PWH in this study received medical care at Valley AIDS Council (VAC) clinic sites located in Harlingen and McAllen, Texas. Henceforth, this cohort will be referred to as Valley AIDS Council Cohort (VACC). Cross-sectional analyses were conducted using retrospective data obtained from 1,827 registries. It included demographic and anthropometric variables, cardiometabolic traits, and HIV-related virological and immunological indices. For descriptive statistics, we used mean values of the quantitative variables from unbalanced visits across 20 months. Robust regression methods were used to determine the associations. For comparisons, we used cardiometabolic trait data obtained from HIV-uninfected San Antonio Mexican American Family Studies (SAMAFS; N = 2,498), and the Mexican American population in the National Health and Nutrition Examination Survey (HHANES; N = 5,989). The prevalence of T2D in VACC was 51% compared to 27% in SAMAFS and 19% in HHANES, respectively. The PWH with T2D in VACC were younger (4.7 years) and had lower BMI (BMI 2.43 units less) when compared to SAMAFS individuals. In contrast, VACC individuals had increased blood pressure and dyslipidemia. The increased T2D prevalence in VACC was independent of BMI. Within the VACC, ART was associated with viral load and CD4+ T cell counts but not with metabolic dysfunction. Notably, we found that individuals with any INSTI combination had higher T2D risk: OR 2.08 (95%CI 1.67, 2.6; p < 0.001). In summary, our results suggest that VACC individuals may develop T2D at younger ages independent of obesity. The high burden of T2D in these individuals necessitates rigorously designed longitudinal studies to draw potential causal inferences and develop better treatment regimens.
Serum Troponin T Concentrations Are Frequently Elevated in Advanced Skin Cancer Patients Prior to Immune Checkpoint Inhibitor Therapy: Experience From a Single Tertiary Referral Center
Authors: Kurzhals Jonas K. , Graf Tobias , Boch Katharina , Grzyska Ulrike , Frydrychowicz Alex , Zillikens Detlef , Terheyden Patrick , Langan Ewan A.
Published: July 2021

Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of several human malignancies, particularly metastatic skin cancer. However, immune-related myocarditis (irM), an immune-mediated adverse event (irAE), is often fatal. In the absence of a reliable biomarker, measurement of pre-ICI therapy serum troponin concentration has been proposed to identify patients at risk of developing irM, although real-world studies examining this strategy are lacking. Thus, we retrospectively analyzed the case records of all patients who commenced ICI therapy between January 2018 and December 2019 in a single university skin cancer center (n = 121) to (i) determine the incidence of irM, (ii) establish the frequency of pretreatment serum hsTnT elevations, and (iii) to establish whether this identified patients who subsequently developed irM. Only one patient developed irM, resulting in an overall incidence of 0.8%. Pretreatment hsTnT was measured in 47 patients and was elevated in 13 (28%). Elevated serum hsTnT concentrations were associated with chronic renal failure (p = 0.02) and diabetes (p < 0.0002). Pretreatment hsTnT was not elevated in the patient who developed fulminant irM. Pre-immunotherapy serum hsTnT concentrations were often asymptomatically elevated in patients with advanced skin cancer, none of whom subsequently developed irM during ICI therapy. However, large studies are required to assess the positive and negative predictive values of hsTnT for the development of irM. In the meantime, elevated hsTnT concentrations should be investigated before initiation of immunotherapy and closely monitored during early treatment cycles, where the risk of irM is greatest.
High Counts and Anthracene Degradation Ability of Streptococcus mutans and Veillonella parvula Isolated From the Oral Cavity of Cigarette Smokers and Non-smokers
Authors: Moussa Hams A. , Wasfi Reham , Abdeltawab Nourtan F. , Megahed Salwa A.
Published: July 2021

The composition and metabolic functions of oral microbiota are affected by many factors including smoking leading to several health problems. Cigarette smoking is associated with changes in oral microbiota composition and function. However, it is not known if the depletion of certain bacterial genera and species is due to specific toxins in cigarette smoke, or indirectly due to competition for colonization with smoking-enriched bacteria. Therefore, the aim of this study was to determine the effect of cigarette smoking on the microbial prevalence and polycyclic aromatic hydrocarbons (PAHs) biodegradation of selected enriched and depleted oral bacteria from oral microbiota of smokers compared to that in non-smokers. Samples of oral rinse from smokers and non-smokers were collected (n = 23, 12 smokers and 11 non-smokers) and screened for oral bacterial strains of Streptococcus mutans, Lactobacillus spp., and Veillonella spp. Comparing counts, S. mutans, V. tobetsuensis, and V. dispar showed higher counts in smokers compared to non-smokers while the Lactobacillus spp. were higher in non-smokers. Lactobacillus fermentum was prevalent in smokers, representing 91.67% of the total Lactobacillus spp. isolates. The biodegradation potential of anthracene; a representative of PAHs of collected isolates, in single and mixed cultures, was assayed with anthracene as the sole source of carbon using 2,6-dichlorophenol indophenol (2,6-DCPIP) as indicator. S. mutans isolates recovered from smokers showed higher degradation of anthracene compared to those recovered from non-smokers. The anaerobic anthracene biodegradation activity of V. parvula isolates from non-smokers was the highest among all isolates of the three recovered genera from the same subject. The anthracene biodegradation potential of Lactobacillus spp. was variable. Combinations of isolated bacteria in co-cultures showed that Lactobacillus spp. interfered with anthracene biodegradation ability along with the viable counts of S. mutans and Veillonella spp. In conclusion, oral dysbiosis due to cigarette smoking was observed not only due to changes in oral bacterial relative abundance but also extended to bacterial functions such as anthracene biodegradation tested in this study. Microbe–microbe interactions changed the anthracene biodegradation potential and growth of the microbial mixture compared to their corresponding single isolates, and these changes differ according to the constituting bacteria.