bluuebunny/crossref_metadata_2025 huggingface dataset:
Pendampingan Kajian Kebutuhan Lahan Tempat Pengelolaan Sampah Terpadu (TPST) 3R di Desa Junrejo
Authors: Orfa Lourina Evanale , Samin  , Sulianto
Published: June 2023

Penanganan sampah baik dari rumah tangga dan sampah sejenisnya perlu melibatkan semua pihak baik pemerintah ataupun masyarakat. Pelaksanaan pemilahan sampah dan melakukan pengurangan jumlah sampah mulai dari rumah ternyata masih kurang efisien. Perlu adanya peningkatan peran dari masyarakat, kelompok masyarakat ataupun dari pemerintah. Penggunaan fasilitas Tempat Pengelolaan Sampah Reduce-Reuse-Recycle (TPS 3R) merupakan salah satu pendekatan pengelolaan sampah. Desa Junrejo masuk ke wilayah Kecamatan Junrejo Kota Batu yang masih belum memiliki TPST yang memadai. Sampah hasil buangan masyarakat langsung dibuang ke TPA Tlekung. Hal ini berdampak pada penumpukan sampah dengan volume yang besar. Untuk mempermudah pihak Desa dalam melaksanakan program pengurangan sampah maka akan dilakukan pendampingan design TPST 3R dan pengelolaan sampah di Desa Junrejo. Pengabdi telah melakukan pendampingan berupa kajian kebutuhan lahan TPST 3R berdasarkan jumlah buangan sampah dari Desa Junrejo. Hasil pendampingan berupa total kebutuhan lahan sebesar 582 m2. Kebutuhan lahan ini penting untuk melanjutkan ke tahapan pengelolaan sampah terpadu yang lebih optimal.
Pelatihan Peningkatan Kompetensi Pengelasan SMAW PT. Garam Sesuai Dengan Standart AWS. D.II di Politeknik Negeri Madura
Authors: Risdianto Anauta Lungiding Angga , M. Musta'in  , Syarifuddin Arief , Prasetyo Taufan , Iswidodo Windra
Published: June 2023

PT Garam merupakan salah satu perusahaan yang berada di Pulau Madura. Saat ini sedang dilakukan penigkatan kompetensi bagi pegawai dengan berkolaborasi antara POLTERA dengan perusahaan. Hal ini dilakukan karena sampang pada nilai IPM sebesar 61,9%. Tujuan dari pengabdian masyarakat ini untuk meningkatkan keterampilan pegawai khususnya pada bidang pengelasan dan inspeksi menggunakan metode penetran. Kegiatan ini dilaksanakan di Politeknik Negeri Madura dengan jumlah peserta 10 orang. Besar harapan pada kegiatan ini dapat dialksanakan secara teratur agar semakin banyak karyawan yang mendapatkan kompetensi khususnya pada bidang inspeksi pengelasan. Pada beberapa kegiatan telah dilakukan tes dan evaluasi untuk mengetahui pemehaman peserta. Hasil dari ujian tulis yang dilakukan dengan rata rata nilai 73 dan presentasi pemahanan 90%. Selanjunya dilakukan evaluasi berupa praktek pengelasan dan penetran tes yaitu dapat mengidentifikasi cacat permukaan pada hasil las. Maka, setelah silaksanakan kegiatan ini peserta yang hadir dapat mengaplikasikan ilmu yang didapatkan terutama pada pekerjaan di perusahaan PT Garam untuk perbaikan mesin dan konstruksi.
Pendampingan Orang Tua dalam Mendukung Transisi PAUD Ke SD di Raudhatul Atfhfal (RA) Masyithoh, Semuluh, Gunungkidul
Authors: Lestari Dwi Puji
Published: June 2023

Transisi PAUD ke SD merupakan fase penting bagi anak. Masa transisi anak belum memiliki kesiapan untuk menerima proses belajar di SD. Jika fase transisi gagal maka akan gagal dalam proses belajar berikutnya. Peran orang menjadi faktor penting dalam mendukung fase transisi. Tujuan pengabdian masyarakat untuk memberikan bekal dukungan orang tua kepada anak yang akan mengalami transisi PAUD ke Sekolah Dasar. Metode pelaksanaan dalam pengabdian ini melalui 1) analisis situasi dengan melakukan dialog kepada orang tua terkait dengan kesiapan untuk mendukung anak memasuki jenjang SD, 2) melakukan rancangan program pendampingan untuk memberikan bekal pengetahuan untuk orang tua, 3) melaksanakan pengabdian, 4) melakukan evaluasi pengabdian dengan melakukan refleksi bersama. Hasil dari pengabdian ini adalah orang tua dapat memahami praktik baik dalam pendampingan transisi anak dari jenjang SD ke PAUD.
COENZYME Q0 INHIBITS CELL PROLIFERATION AND MODULATES MAPK AND AKT SIGNALLING PATHWAYS IN HUMAN CHRONIC MYELOID LEUKEMIA K562 CELLS
Authors: KAYA SEZGİNER Ecem , YAPRAK Ali , KARABAY Arzu Zeynep
Published: June 2023

Objective: This study evaluated the antiproliferative and pro-apoptotic effects of coenzyme Q0 (CoQ0) in human chronic myeloid leukemia K562 cell line.
Material and Method: The cytotoxic effect of CoQ0 on human chronic myeloid leukemia cell line, K562 was determined by MTT test. The activity of caspase-3, expression of proteins involved in apoptosis, MAPK and AKT signaling pathways were determined with enzymatic assay and western blot analysis, respectively.
Result and Discussion: Results showed that CoQ0 inhibited cell viability of K562 cells at 5 μM and higher concentrations and Bax protein expression was significantly decreased at 12.5 μM concentration of CoQ0. However, CoQ0 did not significantly affect caspase 3 activity and Bcl-2 protein expression. p-c-Raf (Ser259) protein expression was significantly decreased at 12.5 μM of CoQ0. Treatment with 10 μM of CoQ0 induced significantly phosphorylation of p38 MAPK and 12.5 μM CoQ0 caused a nonsignificant decrease in p-ERK1/2 protein expression in K562 cell line. Interestingly, in K562 cells, phosphorylation of Akt (Ser473) was diminished at 12.5 μM of CoQ0, with no change observed in p-Akt (Thr308) protein expression among groups. In conclusion, CoQ0 inhibited cell proliferation and suppressed phosphorylation of c-Raf (Ser259), Akt (Ser473), but not ERK1/2 in K562 cells. There is still a need for new insights into the anticancer mechanisms of CoQ0 and develop treatment strategies for chronic myeloid leukemia.
Comparing ChatGPT’s ability to rate the degree of stereotypes and the consistency of stereotype attribution with those of medical students in New Zealand in developing a similarity rating test: a methodological study
Authors: Lin Chao-Cheng , Akuhata-Huntington Zaine , Hsu Che-Wei
Published: June 2023

Learning about one’s implicit bias is crucial for improving one’s cultural competency and thereby reducing health inequity. To evaluate bias among medical students following a previously developed cultural training program targeting New Zealand Māori, we developed a text-based, self-evaluation tool called the Similarity Rating Test (SRT). The development process of the SRT was resource-intensive, limiting its generalizability and applicability. Here, we explored the potential of ChatGPT, an automated chatbot, to assist in the development process of the SRT by comparing ChatGPT’s and students’ evaluations of the SRT. Despite results showing non-significant equivalence and difference between ChatGPT’s and students’ ratings, ChatGPT’s ratings were more consistent than students’ ratings. The consistency rate was higher for non-stereotypical than for stereotypical statements, regardless of rater type. Further studies are warranted to validate ChatGPT’s potential for assisting in SRT development for implementation in medical education and evaluation of ethnic stereotypes and related topics.
Contrasting distributional patterns of two co-occurring ctenophores in relation to ichthyoplankton and environmental features in the Southwestern Atlantic Ocean
Authors: Sobrero L , Chiaverano LM , Machinandiarena L , Martos P , Derisio C , Giberto D , Betti P , Leonarduzzi E , Macchi G , Schiariti A
Published: June 2023

Assessing the ecological role of ctenophores is crucial to understanding ecosystem functioning, including the recruitment of fish stocks. During austral summer in the North Patagonia Ecosystem (NPE) (41-48°S), the ctenophores Mnemiopsis leidyi and Pleurobrachia pileus co-occur with the peak of ichthyoplankton abundance of 2 important fishing resources: the Argentine anchovy Engraulis anchoita and the Argentine hake Merluccius hubbsi, in association with a highly productive tidal front system. We analyzed 367 plankton samples collected in the NPE over 13 yr (2005-2018) to determine the abundance and spatial distribution of M. leidyi and P. pileus, their spatial overlap with ichthyoplankton (eggs and larvae of hake and anchovy), and their relationship with environmental features. Both ctenophore species displayed contrasting distributional patterns, associated with different physical environments, particularly temperature. M. leidyi showed a higher spatial overlap with ichthyoplankton compared to P. pileus. In addition, we found a significant negative correlation between the biomass of M. leidyi and the abundance of both fish larvae, suggesting a potential negative impact (via predation and competition) on the survival and recruitment of these 2 fisheries resources.
Discontinuous dynamics in North Sea cod Gadus morhua caused by ecosystem change
Authors: Blöcker AM , Sguotti C , Möllmann C
Published: June 2023

Marine ecosystems worldwide experience abrupt changes and regime shifts in structure and functioning due to the interacting effects of multiple stressors. North Sea codGadus morhuais a key example of a species being strongly overexploited for decades, causing an abrupt stock decrease below scientifically advised sustainable levels. Despite reductions in fishing pressure in recent years, populations of North Sea cod have not yet recovered. Why recovery is hindered and especially how ecosystem dynamics interacted with fishing to create a stable low cod stock is an open question. Here, we sequentially apply change point and principle component analyses as well as stochastic cusp modelling to a long-term time series (1963-2018) to show that North Sea cod recovery is limited due to an interaction of fishing pressure, internal stock dynamics and external environmental changes. We found that cod biomass experienced nonlinear, discontinuous dynamics, given the interaction of fishing pressure and climate change-induced increases in temperatures, wind magnitude and the North Atlantic Oscillation. Our results further demonstrate discontinuity in cod biomass due to low recruitment caused by a discontinuous relationship between stock biomass and environmental changes characterized by climate and zooplankton variables. Our study indicates that climate-induced changes in the environment have trapped North Sea cod in a depleted state, limiting the probability that the population will regain its role as a main target species for fisheries. Hence, we highlight the importance of incorporating discontinuous dynamics in fisheries management approaches to achieve sustainable exploitation levels and to identify thresholds of drivers to favour policies to prevent regime shifts.
Lipopolysaccharide bioengineering in Bordetella species
Authors:   , Perez Ortega Jesus
Published: June 2023

Bordetella pertussis and Bordetella bronchiseptica are pathogenic bacteria responsible for respiratory diseases in mammals, including humans. B. pertussis causes whooping cough in humans, primarily affecting young children. Vaccines against B. pertussis consisting of whole-cell inactivated bacteria were introduced globally in the 1940s, leading to a significant decline in pertussis cases. However, these vaccines had undesired side effects such as fever and convulsions. Concerns regarding the safety of these vaccines resulted in their replacement by acellular vaccines in many high-income countries. Although the acellular vaccines were proven to be effective and presented reduced adverse reactions, the number of pertussis cases has been rising during the past decades in the countries using them. B. bronchiseptica causes respiratory diseases in various mammalian species, including dogs and pigs, and can also infect humans with weakened immune systems. Similar to B. pertussis, whole-cell vaccines against B. bronchiseptica have side effects that impact animal welfare and food production.
The outer membrane of Gram-negative bacteria, including B. pertussis and B. bronchiseptica, contains lipopolysaccharides (LPS) that are responsible for the toxic immunological response during infection (endotoxicity), and its presence in whole-cell vaccines seems to be the main reason for the undesired side effects produced by these formulations. LPS activates the Toll-like receptor 4 (TLR4), which leads to inflammation and, in extreme cases, to septic shock and death. LPS consists of three major components: lipid A, core oligosaccharide, and O-antigen. Lipid A anchors LPS into the bacterial membrane and is responsible for its endotoxic activity. Modifications to the structure of LPS can affect its ability to stimulate TLR4 and its endotoxicity. The development of novel whole-cell vaccines that are genetically detoxified by LPS bioengineering has been on the rise over the last decades because it allows for the production of affordable and effective vaccines with fewer side effects. In this thesis, we sought to reduce whole-cell endotoxicity in B. pertussis and B. bronchiseptica by genetic modifications that altered the LPS structure or decreased LPS levels. We also investigated the consequences of these modifications on the biology of the bacteria.
Keyphrase Extraction on Covid-19 Tweets Based on Doc2Vec and YAKE
Authors: Firdausillah Fahri , Udayanti Erika Devi
Published: June 2023

Keyword and keyphrase extraction are one of the initial foundations for performing several text processing operations such as summarization and document clustering. YAKE is one of the techniques used for unsupervised and independent keyphrase extraction, it does not require a corpus for linguistic tools such as NER and POS-tag. However, the use of YAKE in microblogging documents such as Twitter often results in a keyphrase that is less representative because of the lack of words used for ranking. This paper offers a solution to this problem by looking for similar tweets in the keyphrase extraction process using Doc2Vec so that the number of words used in the YAKE ranking process can be greater. Covid-19 tweets related are used as dataset as the topic is currently widely discussed on social media to prove that the proposed approach could improve keyphrase extraction performance
Implementation of Temperature and Humidity Control Devices in IOT-Based Hydrophonic Peppermint Cultivation at Sufiagrifarm Slawi
Authors: Maulana Donny , Afriantoro Irfan
Published: June 2023

Along with the rapid development of existing technology, especially in the field of information and the Internet of Thinks ( IoT ), which is developing so fast and producing a lot of benefits to help humans both in the field of education and in manufacturing and agriculture. But at this time there are still so many technologies that still cannot be implemented in certain fields, for example like agriculture, where everything is still done manually so that it takes a lot of time, costs and also more energy in the process. Such as the constraints that exist with Sufiagrifarm, where in this case to meet the needs of temperature and humidity in Peppermint plants that use a hydrophonic planting system it is still done manually by spraying the plants with a spray that produces dew. Given these problems, this research aims to assist Sufiagrifarm in overcoming problems in regulating temperature and humidity in peppermint plants so that temperature and humidity compliance in peppermint plants can be carried out automatically and can be monitored in real time. Development in this method is carried out using the SDLC Waterfall method. This application was created using the Java programming language using the MITApp inventor platform, for the tool itself it was made using an Arduino microcontroller with the C programming language supported by several other devices such as Thingspeak. The results of this study are to help fulfill temperature and humidity in peppermint cultivation at Sufiagrifarm.
Looking beyond the Laws: Disjuncture between LGBTQ+ Laws and Conditions in Ecuador
Authors: Vaca Carolyn
Published: June 2023

Despite Ecuador's progressive laws, there continues to be violence against LGBTQ+ communities. This article analyzes current conditions through the lens of three main areas of life: LGBTQ+ stability and mobility, basic necessities, and safety. It demonstrates that a lack of government enforcement of laws creates constant barriers for LGBTQ+ community members. The work of activists, NGO, NPO, media publications, and intergovernmental organizations is crucial in analyzing the reality of these conditions. Along with the continued progress legislatively and judicially, there needs to be enforcement of these protections, and work put in to drive a social and cultural shift for the protection and progression of LGBTQ+ communities. Furthermore, this article seeks to provide supporting evidence for asylum applicants from countries such as Ecuador by highlighting to United States Citizenship and Immigration Services (USCIS) and immigration judges that Ecuadorian laws may not be an accurate reflection of conditions within Ecuador.
Critical feedback from artists: initial findings of the impact of the health crisis on the field of art and culture
Authors: Chêne Aurélie , Montero Sarah
Published: June 2023

Our research project aims to study the impact of the Covid crisis on the professional cultural sector in the Nouvelle-Aquitaine region. To achieve this objective, the research team has joined forces with several stakeholders in a participatory process. Initial consultations with artists from various disciplines show that the crisis has affected the relationship to time and space in terms of the creative process and the relationship to audiences and inhabitants. It also reveals the need to rethink the organisation of the cultural system in order to better support artists and include them in the decision-making process.
Gene SH3BGRL3 regulates acute myeloid leukemia progression through circRNA_0010984 based on competitive endogenous RNA mechanism
Authors: Yang Xiancong , Wang Yaoyao , Rong Simin , An Jiayue , Lan Xiaoxu , Yin Baohui , Sun Yunxiao , Wang Pingyu , Tan Boyu , Xuan Ye , Xie Shuyang , Su Zhenguo , Li Youjie
Published: June 2023

Introduction: Acute myeloid leukemia (AML) is a malignant proliferative disease affecting the bone marrow hematopoietic system and has a poor long-term outcome. Exploring genes that affect the malignant proliferation of AML cells can facilitate the accurate diagnosis and treatment of AML. Studies have confirmed that circular RNA (circRNA) is positively correlated with its linear gene expression. Therefore, by exploring the effect of SH3BGRL3 on the malignant proliferation of leukemia, we further studied the role of circRNA produced by its exon cyclization in the occurrence and development of tumors.

Methods: Genes with protein-coding function obtained from the TCGA database. we detected the expression of SH3BGRL3 and circRNA_0010984 by real-time quantitative polymerase chain reaction (qRT-PCR). We synthesized plasmid vectors and carried out cell experiments, including cell proliferation, cell cycle and cell differentiation by cell transfection. We also studied the transfection plasmid vector (PLVX-SHRNA2-PURO) combined with a drug (daunorubicin) to observe the therapeutic effect. The miR-375 binding site of circRNA_0010984 was queried using the circinteractome databases, and the relationship was validated by RNA immunoprecipitation and Dual-luciferase reporter assay. Finally, a protein‐protein interaction network was constructed with a STRING database. GO and KEGG functional enrichment identified mRNA-related functions and signaling pathways regulated by miR-375.

Results: We identified the related gene SH3BGRL3 in AML and explored the circRNA_0010984 produced by its cyclization. It has a certain effect on the disease progression. In addition, we verified the function of circRNA_0010984. We found that circSH3BGRL3 knockdown specifically inhibited the proliferation of AML cell lines and blocked the cell cycle. We then discussed the related molecular biological mechanisms. CircSH3BGRL3 acts as an endogenous sponge for miR-375 to isolate miR-375 and inhibits its activity, increases the expression of its target YAP1, and ultimately activates the Hippo signaling pathway involved in malignant tumor proliferation.

Discussion: We found that SH3BGRL3 and circRNA_0010984 are important to AML. circRNA_0010984 was significantly up-regulated in AML and promoted cell proliferation by regulating miR-375 through molecular sponge action.
Establishment of the multi-component bone-on-a-chip: to explore therapeutic potential of DNA aptamers on endothelial cells
Authors: Fan Xiaoyu , Yan Yuhan , Zhao Lianhui , Xu Xin , Dong Yiyang , Sun Wei
Published: June 2023

Background: Despite great efforts to develop microvascular bone chips in previous studies, current bone chips still lacked multi-component of human-derived cells close to human bone tissue. Bone microvascular endothelial cells (BMECs) were demonstrated to be closely related to the glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). Tumor necrosis factor-alpha (TNF-α) aptamer has been proved to bind to its receptor and block cascade activities.

Objective: There are two main objectives in this study: 1) to establish a multi-component bone-on-a-chip within the microfluidic system in vitro, 2) to explore the therapeutic potential of TNF-α aptamer on BMECs in the GC-induced ONFH model.

Methods: Histological features of clinical samples were analyzed before BMECs isolation. The functional bone-on-a-chip consists of the vascular channel, stromal channel and structure channel. GC-induced ONFH model was established based on the multi-component of human-derived cells. Truncation and dimerization were performed on a previously reported DNA aptamer (VR11). BMECs apoptosis, cytoskeleton and angiogenesis status in the ONFH model were observed by the TUNEL staining and confocal microscope.

Results: The multi-component of BMECs, human embryonic lung fibroblasts and hydroxyapatite were cultured within the microfluidic bone-on-a-chip. TNF-α was found up-regulated in the necrotic regions of femoral heads in clinical samples and similar results were re-confirmed in the ONFH model established in the microfluidic platform by detecting cell metabolites. Molecular docking simulations indicated that the truncated TNF-α aptamer could improve the aptamer-protein interactions. Further results from the TUNEL staining and confocal microscopy showed that the truncated aptamer could protect BMECs from apoptosis and alleviate GC-induced damages to cytoskeleton and vascularization.

Conclusion: In summary, a microfluidic multi-component bone-on-a-chip was established with ‘off-chip’ analysis of cell metabolism. GC-induced ONFH model was achieved based on the platform. Our findings provided initial evidence on the possible potentials of TNF-α aptamer as a new type of TNF-α inhibitor for patients with ONFH.
Fructus gardeniae ameliorates anxiety-like behaviors induced by sleep deprivation via regulating hippocampal metabolomics and gut microbiota
Authors: Liu Dong , Wang Qianfei , Li Ying , Yuan Zhenshuang , Liu Zhiliang , Guo Junli , Li Xin , Zhang Weichao , Tao Yulei , Mei Jianqiang
Published: June 2023

Fructus gardeniae (FG) is a traditional Chinese medicine and health food for thousands of years of application throughout Chinese history and is still widely used in clinical Chinese medicine. FG has a beneficial impact on anxiety, depression, insomnia, and psychiatric disorders; however, its mechanism of action requires further investigation. This study aimed to investigate the effects and mechanisms of FG on sleep deprivation (SD)-induced anxiety-like behavior in rats. A model of SD-induced anxiety-like behavior in rats was established by intraperitoneal injection of p-chlorophenylalanine (PCPA). This was accompanied by neuroinflammation and metabolic abnormalities in the hippocampus and disturbance of intestinal microbiota. However reduced SD-induced anxiety-like behavior and decreased levels of pro-inflammatory cytokines including TNF-α and IL-1β were observed in the hippocampus of rats after 7 days of FG intervention. In addition, metabolomic analysis demonstrated that FG was able to modulate levels of phosphatidylserine 18, Phosphatidylinositol 18, sn-glycero-3-phosphocholine, deoxyguanylic acid, xylose, betaine and other metabolites in the hippocampus. The main metabolic pathways of hippocampal metabolites after FG intervention involve carbon metabolism, glycolysis/gluconeogenesis, pentose phosphate, and glycerophospholipid metabolism. 16S rRNA sequencing illustrated that FG ameliorated the dysbiosis of gut microbiota in anxious rats, mainly increased the abundance of Muribaculaceae and Lactobacillus, and decreased the abundance of Lachnospiraceae_NK4A136_group. In addition, the correlation analysis demonstrated that there was a close relationship between hippocampal metabolites and intestinal microbiota. In conclusion, FG improved the anxiety behavior and inhibited of neuroinflammation in sleep-deprived rats, and the mechanism may be related to the FG regulation of hippocampal metabolites and intestinal microflora composition.
Clinical and bi-genomic DNA findings of patients suspected to have mitochondrial diseases
Authors: Gedikbasi Asuman , Toksoy Guven , Karaca Meryem , Gulec Cagri , Balci Mehmet Cihan , Gunes Dilek , Gunes Seda , Aslanger Ayca Dilruba , Unverengil Gokcen , Karaman Birsen , Basaran Seher , Demirkol Mubeccel , Gokcay Gulden Fatma , Uyguner Zehra Oya
Published: June 2023

Background: Mitochondrial diseases are the most common group of inherited metabolic disorders, causing difficulties in definite diagnosis due to clinical and genetic heterogeneity. Clinical components are predominantly associated with pathogenic variants shown in nuclear or mitochondrial genomes that affect vital respiratory chain function. The development of high-throughput sequencing technologies has accelerated the elucidation of the genetic etiology of many genetic diseases that previously remained undiagnosed.

Methods: Thirty affected patients from 24 unrelated families with clinical, radiological, biochemical, and histopathological evaluations considered for mitochondrial diseases were investigated. DNA isolated from the peripheral blood samples of probands was sequenced for nuclear exome and mitochondrial DNA (mtDNA) analyses. MtDNA sequencing was also performed from the muscle biopsy material in one patient. For segregation, Sanger sequencing is performed for pathogenic alterations in five other affected family members and healthy parents.

Results: Exome sequencing revealed 14 different pathogenic variants in nine genes encoding mitochondrial function peptides (AARS2, EARS2, ECHS1, FBXL4, MICOS13, NDUFAF6, OXCT1, POLG, and TK2) in 12 patients from nine families and four variants in genes encoding important for muscle structure (CAPN3, DYSF, and TCAP) in six patients from four families. Three probands carried pathogenic mtDNA variations in two genes (MT-ATP6 and MT-TL1). Nine variants in five genes are reported for the first time with disease association: (AARS2: c.277C>T/p.(R93*), c.845C>G/p.(S282C); EARS2: c.319C>T/p.(R107C), c.1283delC/p.(P428Lfs*); ECHS1: c.161G>A/p.(R54His); c.202G>A/p.(E68Lys); NDUFAF6: c.479delA/p.(N162Ifs*27); and OXCT1: c.1370C>T/p.(T457I), c.1173-139G>T/p.(?).

Conclusion: Bi-genomic DNA sequencing clarified genetic etiology in 67% (16/24) of the families. Diagnostic utility by mtDNA sequencing in 13% (3/24) and exome sequencing in 54% (13/24) of the families prioritized searching for nuclear genome pathologies for the first-tier test. Weakness and muscle wasting observed in 17% (4/24) of the families underlined that limb-girdle muscular dystrophy, similar to mitochondrial myopathy, is an essential point for differential diagnosis. The correct diagnosis is crucial for comprehensive genetic counseling of families. Also, it contributes to making treatment-helpful referrals, such as ensuring early access to medication for patients with mutations in the TK2 gene.
Apoptosis-mediated inhibition of human T-cell acute lymphoblastic leukemia upon treatment with Staphylococus Aureus enterotoxin-superantigen
Authors: Duarte Alejandra , Montagna Daniela R. , Pastorini Mercedes , Alemán Mercedes
Published: June 2023

Patients with relapsed T cell acute lymphoblastic leukemia (T-ALL) have limited therapeutic options and poor prognosis. The finding of efficient strategies against this refractory neoplasm is a medical priority. Superantigens (SAgs) are viral and bacterial proteins that bind to major histocompatibility complex class II molecules as unprocessed proteins and subsequently interact with a high number of T cells expressing particular T cell receptor Vβ chains. Although on mature T cells, SAgs usually trigger massive cell proliferation producing deleterious effects on the organism, in contrast, on immature T cells, they may trigger their death by apoptosis. On this basis, it was hypothesized that SAgs could also induce apoptosis in neoplastic T cells that are usually immature cells that probably conserve their particular Vβ chains. In this work, we investigated the effect of the SAg Staphylococcus aureus enterotoxin E (SEE) (that specifically interacts with cells that express Vβ8 chain), on human Jurkat T- leukemia line, that expresses Vβ8 in its T receptor and it is a model of the highly aggressive recurrent T-ALL. Our results demonstrated that SEE could induce apoptosis in Jurkat cells in vitro. The induction of apoptosis was specific, correlated to the down regulation of surface Vβ8 TCR expression and was triggered, at least in part, through the Fas/FasL extrinsic pathway. The apoptotic effect induced by SEE on Jurkat cells was therapeutically relevant. In effect, upon transplantation of Jurkat cells in the highly immunodeficient NSG mice, SEE treatment reduced dramatically tumor growth, decreased the infiltration of neoplastic cells in the bloodstream, spleen and lymph nodes and, most importantly, increased significantly the survival of mice. Taken together, these results raise the possibility that this strategy can be, in the future, a useful option for the treatment of recurrent T-ALL.
Modification of Pacific water in the northern Canadian Arctic
Authors: Dmitrenko Igor A. , Kirillov Sergei A. , Rudels Bert , Geilfus Nicolas-Xavier , Ehn Jens , Babb David G. , Lilien David A. , Dahl-Jensen Dorthe
Published: June 2023

The oceanography of the northern Canadian Arctic Archipelago (CAA) remains poorly studied. Here we present a unique set of conductivity–temperature–depth (CTD) and nitrate profiles collected in a fjord system around Axel Heiberg Island in the northern CAA during April–May 2022. The profiles are examined within the context of upstream observations in the Arctic Ocean and downstream observations in the central CAA, and reveal the origin of water masses and their interactions with ambient water from the continental slope and the nearby tidewater glacier outlet. The subsurface water (~25–180 m depth) is associated with the Pacific water outflow from the Arctic Ocean. The underlying halocline separates Pacific water from a deeper layer of polar water that has interacted with the warm (>0°C) Atlantic water observed below 240 m depth. Pacific water is significantly modified compared to the adjoining Arctic Ocean, as evidenced by the following details. Cold water intrusions from the tidewater glacier create deviations of ~0.25°C in the temperature profile through the subsurface water down to a depth of 140 m. Profiles show no thermal signature of Pacific summer water. Compared to the adjacent Arctic Ocean, the deeper fraction of Pacific-derived water and the Atlantic-modified polar water are warmer, while the underlying Atlantic water is colder. Overall, our results suggest that Pacific and Atlantic water in this area of the northern CAA are modified due to enhanced vertical mixing in a narrow band over the continental slope and shelf off the CAA, and are further modified by interactions with outlet glaciers in the area. This implies that tracing the initial thermohaline signature of the Pacific and Atlantic water flow through the CAA seems to be hardly possible without the use of additional tracers. We also find evidence of geothermal heating near the seafloor, which is not surprising given the observed presence of terrestrial geothermal vents around Axel Heiberg Island, and speculate this heat flux limits ice growth near the glacier terminus.
Conserved organ-specific microbial assemblages in different populations of a terrestrial crab
Authors: Bacci Giovanni , Fratini Sara , Meriggi Niccolò , Cheng Christine L. Y. , Ng Ka Hei , Pindo Massimo , Iannucci Alessio , Mengoni Alessio , Cavalieri Duccio , Cannicci Stefano
Published: June 2023

Microorganisms are ubiquitous in the environment and provide genetic and physiological functions to multicellular organisms. Knowledge on the associated microbiota is becoming highly relevant to understand the host’s ecology and biology. Among invertebrates, many examples of endosymbiosis have been described, such as those in corals, ants, and termites. At present, however, little is known on the presence, diversity, and putative roles of the microbiota associated to brachyuran crabs in relation to their environment. In this work we investigated the associated microbiota of three populations of the terrestrial brachyuran crab Chiromantes haematocheir to find evidence of a conserved organ-specific microbiome unrelated to the population of origin and dissimilar from environmental microbial assemblages. Bacterial 16S rRNA gene and fungal ITS sequences were obtained from selected crab organs and environmental matrices to profile microbial communities. Despite the presence of truly marine larval stages and the absence of a gregarious behaviour, favouring microbiota exchanges, we found common, organ-specific microbiota, associated with the gut and the gills of crabs from the different populations (with more than 15% of the genera detected specifically enriched only in one organ). These findings suggest the presence of possible functional roles of the organ-specific microbiota.
EZH1/2 dual inhibitors suppress HTLV-1-infected cell proliferation and hyperimmune response in HTLV-1-associated myelopathy
Authors: Koseki Akihito , Araya Natsumi , Yamagishi Makoto , Yamauchi Junji , Yagishita Naoko , Takao Naoki , Takahashi Katsunori , Kunitomo Yasuo , Honma Daisuke , Araki Kazushi , Uchimaru Kaoru , Sato Tomoo , Yamano Yoshihisa
Published: June 2023

Background

Human T-cell leukemia virus type 1 (HTLV-1) causes HTLV-1-associated myelopathy (HAM), adult T-cell leukemia/lymphoma (ATL), HTLV-1-associated uveitis, and pulmonary diseases. Although both HAM and ATL show proliferation of infected cells, their pathogeneses are quite different. In particular, the pathogenesis of HAM is characterized by hyperimmune responses to HTLV-1-infected cells. Recently, we demonstrated the overexpression of histone methyltransferase EZH2 in ATL cells and the cytotoxic effects of EZH2 inhibitors and EZH1/2 dual inhibitors on these cells. However, these phenomena have never been studied in HAM. Furthermore, what effect these agents have on the hyperimmune response seen in HAM is completely unknown.

Methods

In this study, we investigated histone methyltransferase expression levels in infected cell populations (CD4+ and CD4+CCR4+ cells) from patients with HAM using microarray and RT-qPCR analyses. Next, using an assay system that utilizes the spontaneous proliferation characteristic of peripheral blood mononuclear cells derived from patients with HAM (HAM-PBMCs), we investigated the effects of EZH2 selective inhibitors (GSK126 and tazemetostat) and EZH1/2 dual inhibitors (OR-S1 and valemetostat, also known as DS-3201), particularly on cell proliferation rate, cytokine production, and HTLV-1 proviral load. We also examined the effect of EZH1/2 inhibitors on the proliferation of HTLV-1-infected cell lines (HCT-4 and HCT-5) derived from patients with HAM.

Results

We found elevated expression of EZH2 in CD4+ and CD4+CCR4+ cells from patients with HAM. EZH2 selective inhibitors and EZH1/2 inhibitors significantly inhibited spontaneous proliferation of HAM-PBMC in a concentration-dependent manner. The effect was greater with EZH1/2 inhibitors. EZH1/2 inhibitors also reduced the frequencies of Ki67+ CD4+ T cells and Ki67+ CD8+ T cells. Furthermore, they reduced HTLV-1 proviral loads and increased IL-10 levels in culture supernatants but did not alter IFN-γ and TNF-α levels. These agents also caused a concentration-dependent inhibition of the proliferation of HTLV-1-infected cell lines derived from patients with HAM and increased annexin-V(+)7-aminoactinomycin D(−) early apoptotic cells.

Conclusion

This study showed that EZH1/2 inhibitors suppress HTLV-1-infected cell proliferation through apoptosis and the hyperimmune response in HAM. This indicates that EZH1/2 inhibitors may be effective in treating HAM.
Reliability and validity of the electronic version of the Hopkins verbal learning test-revised in middle-aged and elderly Chinese people
Authors: Jiang Lichen , Xu Ming , Xia Shunyao , Zhu Jiahui , Zhou Qi , Xu Luoyi , Shi Chuan , Wu Daxing
Published: June 2023

Background

The aging population is increasing, making it essential to have a standardized, convenient, and valid electronic memory test that can be accessed online for older people and caregivers. The electronic version of the Hopkins Verbal Learning Test-Revised (HVLT-R) as a test with these advantages and its reliability and validity has not yet been tested. Thus, this study examined the reliability and validity of the electronic version of the HVLT-R in middle-aged and elderly Chinese people to provide a scientific basis for its future dissemination and use.

Methods

We included 1,925 healthy participants aged over 40, among whom 38 were retested after 3–6 months. In addition, 65 participants completed both the pad and paper-and-pencil versions of the HVLT-R (PAP-HVLT-R). We also recruited 42 Alzheimer’s disease (AD) patients, and 45 amnestic mild cognitive impairment (aMCI) patients. All participants completed the Pad-HVLT-R, the Hong Kong Brief Cognitive Test (HKBC), the Brief Visual Memory Test-Revised (BVMT-R), and the Logical Memory Test (LM).

Results

(1) Reliability: the Cronbach’s α value was 0.94, the split-half reliability was 0.96. The test–retest correlation coefficients were moderate, ranging from 0.38 to 0.65 for direct variables and 0.16 to 0.52 for derived variables; (2) Concurrent validity: the Pad-HVLT-R showed a moderate correlation with the HKBC and BVMT-R, with correlation coefficients between total recall of 0.41 and 0.54, and between long-delayed recall of 0.42 and 0.59, respectively. It also showed a high correlation with the LM, with correlation coefficients of 0.72 for total recall and 0.62 for long-delayed recall; (3) Convergent validity: the Pad-HVLT-R was moderately correlated with the PAP version, with correlation coefficients ranging from 0.29 to 0.53 for direct variables and 0.15 to 0.43 for derived variables; (4) Discriminant capacity: the Pad-HVLT-R was effective in differentiating AD patients, as demonstrated by the ROC analysis with AUC values of 0.834 and 0.934 for total recall and long-delayed recall, respectively.

Conclusion

(1) The electronic version of HVLT-R has good reliability and validity in middle-aged and elderly Chinese people; (2) The electronic version of HVLT-R can be used as an effective tool to distinguish AD patients from healthy people.
Predicting DWI-FLAIR mismatch on NCCT: the role of artificial intelligence in hyperacute decision making
Authors: Kim Beom Joon , Zhu Kairan , Qiu Wu , Singh Nishita , McDonough Rosalie , Cimflova Petra , Bala Fouzi , Kim Jongwook , Kim Yong Soo , Bae Hee-Joon , Menon Bijoy K.
Published: June 2023

Background

The presence of diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) mismatch was used to determine eligibility for intravenous thrombolysis in clinical trials. However, due to the restricted availability of MRI and the ambiguity of image assessment, it is not widely implemented in clinical practice.

Methods

A total of 222 acute ischemic stroke patients underwent non-contrast computed tomography (NCCT), DWI, and FLAIR within 1 h of one another. Human experts manually segmented ischemic lesions on DWI and FLAIR images and independently graded the presence of DWI-FLAIR mismatch. Deep learning (DL) models based on the nnU-net architecture were developed to predict ischemic lesions visible on DWI and FLAIR images using NCCT images. Inexperienced neurologists evaluated the DWI-FLAIR mismatch on NCCT images without and with the model’s results.

Results

The mean age of included subjects was 71.8 ± 12.8  years, 123 (55%) were male, and the baseline NIHSS score was a median of 11 [IQR, 6–18]. All images were taken in the following order: NCCT – DWI – FLAIR, starting after a median of 139 [81–326] min after the time of the last known well. Intravenous thrombolysis was administered in 120 patients (54%) after NCCT. The DL model’s prediction on NCCT images revealed a Dice coefficient and volume correlation of 39.1% and 0.76 for DWI lesions and 18.9% and 0.61 for FLAIR lesions. In the subgroup with 15  mL or greater lesion volume, the evaluation of DWI-FLAIR mismatch from NCCT by inexperienced neurologists improved in accuracy (from 0.537 to 0.610) and AUC-ROC (from 0.493 to 0.613).

Conclusion

The DWI-FLAIR mismatch may be reckoned using NCCT images through advanced artificial intelligence techniques.
OPRM1 A118G polymorphism modulating motor pathway for pain adaptability in women with primary dysmenorrhea
Authors: Hsu Pei-Shan , Cheng Chou-Ming , Chao Hsiang-Tai , Lin Ming-Wei , Li Wei-Chi , Lee Lin-Chien , Liu Ching-Hsiung , Chen Li-Fen , Hsieh Jen-Chuen
Published: June 2023

Introduction

Primary dysmenorrhea (PDM) is a common condition among women of reproductive age, characterized by menstrual pain in the absence of any organic causes. Previous research has established a link between the A118G polymorphism in the mu-opioid receptor (OPRM1) gene and pain experience in PDM. Specifically, carriers of the G allele have been found to exhibit maladaptive functional connectivity between the descending pain modulatory system and the motor system in young women with PDM. This study aims to explore the potential relationship between the OPRM1 A118G polymorphism and changes in white matter in young women with PDM.

Methods

The study enrolled 43 individuals with PDM, including 13 AA homozygotes and 30 G allele carriers. Diffusion tensor imaging (DTI) scans were performed during both the menstrual and peri-ovulatory phases, and tract-based spatial statistics (TBSS) and probabilistic tractography were used to explore variations in white matter microstructure related to the OPRM1 A118G polymorphism. The short-form McGill Pain Questionnaire (MPQ) was used to access participants’ pain experience during the MEN phase.

Results

Two-way ANOVA on TBSS analysis revealed a significant main effect of genotype, with no phase effect or phase-gene interaction detected. Planned contrast analysis showed that during the menstrual phase, G allele carriers had higher fractional anisotropy (FA) and lower radial diffusivity in the corpus callosum and the left corona radiata compared to AA homozygotes. Tractographic analysis indicated the involvement of the left internal capsule, left corticospinal tract, and bilateral medial motor cortex. Additionally, the mean FA of the corpus callosum and the corona radiata was negatively correlated with MPQ scales in AA homozygotes, but this correlation was not observed in G allele carriers. No significant genotype difference was found during the pain-free peri-ovulary phase.

Discussion

OPRM1 A118G polymorphism may influence the connection between structural integrity and dysmenorrheic pain, where the G allele could impede the pain-regulating effects of the A allele. These novel findings shed light on the underlying mechanisms of both adaptive and maladaptive structural neuroplasticity in PDM, depending on the specific OPRM1 polymorphism.
Platooning in UAM airspace structures: applying trajectory shaping guidance law and exploiting cooperative localization
Authors: Mayle Melody N. , Sharma Rajnikant
Published: June 2023

A novel control technique for the platooning of aerial vehicles is here introduced, and its stability is analyzed. The controller applies a missile guidance law that was initially adapted for path-following and subsequently extended to platooning. The positions of all agents within a platoon employing this controller are estimated by exploiting cooperative localization, and these estimated positions are fed back into the controller. Using simulation, the agents within a platoon are demonstrated to follow their desired path and avoid collision, even in environments with intermittent Global Positioning System signals and limited sensing ranges.
Early life growth and developmental trajectory in children with biliary atresia undergoing primary liver transplantation
Authors: Fang Heping , Li Zehao , Xian Ruoling , Yin Yu , Wang Juan , Guo Hongling , Dai Xiaoke , Zhang Mingman , Hu Yan , Li Yingcun
Published: June 2023

Objective

To clarify the early growth and developmental characteristics of children with biliary atresia (BA) undergoing primary liver transplantation (pLT).

Methods

A prospective cohort study, which specifically focused on BA-pLT children, was conducted after the diagnosis of BA by following the children at the time of pLT and 1, 3, 5, 7 months and 1 year after pLT for growth and developmental monitoring. The growth parameters were calculated according to the WHO standard, and the developmental status was assessed using Denver Developmental Screening Tests.

Results

A total of 48 BA children who received pLT at the age of 5.00 ± 0.94 months were analyzed. The weight-for-ageZ-value (ZW) and length-for-ageZ-value (ZL) were higher than the head circumference-for-ageZ-value (ZHC) at pLT (P = 0.002 and 0.02), but they were all lower than the WHO growth standard (Z = 0) (P < 0.001). TheZWandZHCdecreased first and then returned to the population level at 1 year after pLT, while theZLonly returned to the preoperative status and was lower than theZWandZHC(P < 0.001). Developmental screening showed that 35% (17/48) of the children were defined as suspicious and 15% (7/48) were abnormal at 1–4 months after pLT, the most likely time to be suspected of developmental delay. At 1 year after pLT, gross motor skill delay still existed (12/45, 27%), and language skill delay began to appear (4/45, 9%).

Conclusions

BA-pLT children suffer from growth and developmental problems. LowZHCis the main growth problem before pLT, while lowZLis the problem after pLT. Developmental delays are significant after pLT, especially in motor and language skills. The current study suggested that further studies are warranted to clarify the long-term growth and developmental outcomes of BA-pLT children, to compare them with children undergoing the Kasai procedure and to explore their influencing factors and possible mechanisms.
Bifunctional antibiotic hybrids: A review of clinical candidates
Authors: Koh Augustine Jing Jie , Thombare Varsha , Hussein Maytham , Rao Gauri G. , Li Jian , Velkov Tony
Published: June 2023

Antibiotic resistance is a top threat to human health and a priority across the globe. This problematic issue is accompanied by the decline of new antibiotics in the pipeline over the past 30 years. In this context, an urgent need to develop new strategies to combat antimicrobial resistance is in great demand. Lately, among the possible approaches used to deal with antimicrobial resistance is the covalent ligation of two antibiotic pharmacophores that target the bacterial cells through a dissimilar mode of action into a single hybrid molecule, namely hybrid antibiotics. This strategy exhibits several advantages, including better antibacterial activity, overcoming the existing resistance towards individual antibiotics, and may ultimately delay the onset of bacterial resistance. This review sheds light on the latest development of the dual antibiotic hybrids pipeline, their potential mechanisms of action, and challenges in their use.