bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of a tamoxifen-RACK7/KDM5C-IFN-I axis for ER+ breast cancer immunomodulation.
Authors: Aberin Marvin Angelo Esteban , Singh Saurabh , Lee Yu-Ling , Lin Kun-Yuan , Chang Yao-Ming , Guha Chandan , Wang Shu-Ping
Published: August 2024

9

Background: ER+ breast cancer patients generally have good prognosis. However, significant relapse rates (i.e., hormone drugs, Tamoxifen/TMX) and the poor response to immune checkpoint blockade (ICB) remain critical issues to be addressed. Thus, exploration of anti-ICB resistant mechanisms and alternative targets is needed to improve therapeutic efficacy. Methods: To investigate potential cross-resistant mechanisms between hormone and ICB therapy, ER+ cell lines T47D and MCF7 cells were chronically-treated with TMX for 6 months, and subjected to RNA-Seq and pathway enrichment analysis. Dysregulation of identified factors were validated via western blotting, RT-qPCR, and flow cytometry. Target factors were then inhibited or depleted by shRNA knockdown (KD) or small-compound inhibition. Identified ICB resistance mechanisms were further elaborated by in vitro co-culture assays, syngeneic mouse models, and immune-profiling of tumor microenvironment (TME). Results: Chronic exposure to TMX activates Type I interferon (IFN-I) signaling, induces IFN I-stimulated gene (ISG) expression, and downregulates the H3K4 demethylase and ISG repressor complex known as RACK7/KDM5C. Chronic TMX also upregulates CEACAM1, a well-known ligand for the immune checkpoint receptor TIM3. Results prompt us to evaluate whether loss of RACK7 combined with TMX treatment may modulate a lymphocyte-attractive (via IFN-I), but T-cell exhaustive (via CEACAM1-TIM3) TME. Indeed, in vitro treatment of TMX under RACK7-KD conditions triggers STING upregulation, TBK1 hyperphosphorylation, and a more pronounced activation of ISGs and CEACAM1. In vivo, TMX combined with RACK7-KD enhances tumor growth in the TS/A (ER+) syngeneic mouse model, while immune-profiling reveal that this combination promotes lymphocyte infiltration with a higher population of terminally exhausted CD8+ T-cells in the TME. Conclusions: Our data demonstrate that the TMX-induced activation of cGAS/STING pathway and RACK7 downregulation coordinately shape the IFN-I and immune checkpoint signaling axes in ER+ breast cancer. This TMX–RACK7–IFN-I regulatory network promotes a lymphocyte-attractive TME via IFN-I signaling activation, whereas induction of inhibitory ligands renders T-cells to be terminally-exhausted and unable to kill tumors. These findings highlight the potential use of TMX’s STING-agonistic effect in re-shaping the “cold” breast cancer TME, and the use of combined TMX and anti-TIM3 or anti-CEACAM1 blockade to improve ICB therapy.
A potent and selective pan-RAS inhibitor, ADT-1004, targeting complex KRAS mutations for pancreatic cancer.
Authors: Piazza Gary , Bandi Reddy DS , Foote Jeremy B , Keeton Adam B , Mattox Tyler Ernest , Chen Xi , Maxuitenko Yulia , Manne Upender , Boyd Michael R , Buchsbaum Donald J , El-Rayes Bassel F.
Published: August 2024

90

Background: Pancreatic ductal adenocarcinoma (PDAC) is a challenging cancer with a 5-year survival rate of under 12%. More than 90% of PDAC cases involve KRAS mutations. KRASG12C inhibitors recently developed have limited use because only 3% of PDAC express this mutation, highlighting the urgent need for pan-RAS inhibitors to address the complex mutation landscape in PDAC while avoiding resistance mechanisms. We synthesized and evaluated a novel pan-RAS inhibitor, ADT-1004, in mouse tumor models transplanted with mouse PDAC cell lines or patient-derived xenografts. ADT-1004 is an orally bioavailable prodrug of ADT-007, a highly potent and selective pan-RAS inhibitor (doi.org/10.1101/2023.05.17.541233). Methods: Human and mouse PDAC cell lines were utilized to evaluate in vitro growth inhibitory potency and selectivity of ADT-007. For in vivo experiments, KPC-Luc (1 × 105) and 2838C3-Luc (1.5 × 105) PDAC cells harboring the KRASG12D mutation were injected into the pancreas of C57BL/6J mice. After one week, the mice were randomly divided into treatment groups (n = 7 per group) and received oral ADT-1004 at a dose of 40mg/kg body weight five times a week for 4 weeks. Tumor burden was assessed weekly by monitoring bioluminescence signals using the IVIS Xenogen imaging system. Four patient-derived xenografts from PDAC patients with KRASG12C, KRASG12D, KRASG12V, KRASG13Q mutations were subcutaneously implanted in NSG mice by a small incision in the right flank. A week later, when the tumors reached a size of 100mm3 mice were randomized (n=7 per group) and treated orally with 40mg/kg of ADT-1004 five times a week for 6 weeks. Body weight and tumor size were measured twice weekly. Results: ADT-007 potently and selectively inhibited the growth of human and mouse PDAC cell lines. For example, the IC50 value pf ADT-007 for KRASG12C MIA PaCA-2 PDAC cells was as low as 2 nM compared to 2500 nM for RASWT BxPC3 PDAC cells. Growth inhibition was dependent on activated RAS and associated with reduced GTP-RAS levels and MAPK/AKT signaling. ADT-1004 was well tolerated in mice at a dose up to 175 mg/kg bid orally with sustained plasma levels of ADT-007 far exceeding growth IC50 values. When administered orally at 40 mg/kg body weight, ADT-1004 displayed robust antitumor activity in mouse tumor models using patient or mouse derived PDAC cell lines with G12D, G12V, G12C, or G13Q KRAS mutations, causing significant inhibitory effects on ERK phosphorylation. Conclusions: ADT-1004 inhibited tumor growth of KRAS mutant PDA tumors by targeting activated RAS to disrupt downstream MAPK/AKT signaling. The results highlight the promise of ADT-1004 as a novel pan-RAS inhibitor and open new strategies for addressing the complex genetic landscape of PDAC and other RAS driven cancers.
Efficacy assessment of a novel pan-RAS inhibitor in KRAS-mutant and wild type colorectal 3D bioprinted organoid tumor tissue.
Authors: Ahirwar Parmanand , Charania Areesha A. , Zuaiter Dana , Eiler Logan C. , Nizamuddin Alyssa , Crawford Chelsea L. , Maxuitenko Yulia Y. , Piazza Gary , Budhwani Karim I.
Published: August 2024

91

Background: Colorectal cancer (CRC) is the third leading type of cancer worldwide, with ~150,000 new cases in the US annually and a grim 14% 5-year survival for patients diagnosed at a late stage. A lack of treatment options leads to persistently poor prognosis for patients with advanced stage disease. KRAS mutations are well known drivers of CRC and other GI cancers. Multiple KRAS mutations occur in CRC, including G12D (34%), G12V (21%), G13D (20%), G12C (8%), and others (18%). Existing KRAS-targeted therapies have limited use in CRC, underscoring the need for pan-RAS inhibitors in treating CRC and other RAS driven cancers. Objective: Assess activity of ADT-007, our pan-RAS inhibitor, on wild-type (WT) and KRAS-mutant 3D bioprinted organoid tumor (BOT) tissue using our high-throughput ex vivo platform. Methods: Using previously established bioprinting protocols, WT and mutant BOTs were printed with HT29 and HCT116 cells, respectively. HT29 is an established human WT CRC cell line with known sensitivity to proteosome and survivin inhibitors. HCT116 is a KRASG13D mutant human CRC cell line. 3 sets of BOTs were generated and acclimated for 24h. One set was treated for 72h with proteosome inhibitor Bortezomib, another with survivin inhibitor YM155, and the third with our novel pan-RAS inhibitor ADT-007. Dose response curves were generated from both conventional ATP luminescence readouts and high-content imaging. Results: BOT tissue microarchitecture was validated and >200 µm diffusion in BOTs was confirmed using high-content imaging. Differential response was quantified using Cell TiterGlo endpoint assay as well as advanced image processing of high-content live/dead nuclear stained images captured at multiple z-plains. ADT-007 IC50 was found to be substantially lower for mutant HCT116 compared to that for WT HT29 cell line BOTs, which was consistent with separately conducted in vitro and in vivo studies. Conclusions: A pan-RAS inhibitor, such as ADT-007 with high selectivity for cancer cells with activated RAS that is not limited to a specific KRAS mutant allele or RAS isozyme, could have broader use for CRC and other RAS-driven cancers. Further, due to their potential to replicate biophysical characteristics of a tumor and its microenvironment, BOT based precision and personalized medicine platforms can provide more accurate drug efficacy readout compared to in vitro cancer models.
Observational study examining the feasibility of generating real-world evidence (RWE) for new drug applications from the clinical trials database (DB; RELIASE study).
Authors: Bando Hideaki , Misumi Toshihiro , Sakamoto Yasutoshi , Takeda Yuriko , Nakamura Yoshiaki , Mizuguchi Kazuya , Aoyagi Yoshihiro , Miki Izumi , Yoshino Takayuki , Ohtsu Atsushi
Published: August 2024

TPS100

Background: The extraction of the data that contributes to regulatory approval from real-world data (RWD) are difficult due to the lack of standardized data format as well as the extraction methodology. In addition, when RWE is used as an external control group, the similarity between internal and external control data has not been evaluated. Methods: In our ‘REALISE’ study, we will investigate the data extraction methodology as external control data of rare molecular subtype. We also elucidate the 'quality' and 'reliability' of RWD/RWE necessary for regulatory submissions. In addition, as most databases are not designed for regulatory use in the creation phase, we will investigate the retrospective methodologies to ensure reliability of RWD/RWE. We compare ‘data quality’ and ‘data reliability’ of ARCAD global DB (N=45,224), SCRUM-Japan registry (N=546), SCRUM-Japan observational study (N=14,325), and the Flatiron health RWD in Japan (N=650) and statistically analyze the differences and similarities among 4 databases. All analyses will be summarized descriptively. Similarity of patient characteristics and efficacy endpoints such as response rate, progression-free survival, overall survival, and all available endpoints will be evaluated by cancer type, treatment line, and standard treatment. For colorectal cancer, data extracted from the SCRUM-Japan registry, SCRUM-Japan observational study, and the Flatiron health RWD will be compared with data extracted from randomized controlled trials in the ARCAD global DB to examine the availability as an external control of RWD. The Kaplan-Meier method will be applied to estimate the survival distribution of time-to-event data. No imputation method for missing data will be used, and the frequency of missing data will also be summarized. We will also examine the methodology for extracting data with sufficient quality from the SCRUM-Japan observational study. In addition, if the reliability of RWD/RWE does not reach the required level, we will also examine the methodologies to retrospectively assure the reliability of the SCRUM-Japan observational study for regulatory submissions. [Table: see text]
Stronger together: Implementing patient-reported symptom tool in routine cancer care in diverse Asia—A multi-national pilot feasibility study (PROMiSE-Pilot).
Authors: Sitthideatphaiboon Piyada , Zaheed Milita , Co Jayson L. , Chua Kevin Lee Min , Malik Monica
Published: August 2024

TPS180

Background: Patients diagnosed with cancer often experience disease or treatment-related symptoms, which can be under-elicited and under-appreciated by clinicians during time-poor consultations. This is particularly challenging in Asia where structural disparities in healthcare access mean oncology services are often under-resourced. Five oncologists from Thailand, India, Singapore, Philippines and Australia formed a working group as part of ASCO Asia-Pacific Leadership Development Program (LDP-AP). Systematic symptom monitoring using patient-reported outcomes measures (PROM) was identified as a potential solution to improve care in diverse Asian settings. PROM has demonstrated improved outcomes in Western settings but its utility in resource limited Asian contexts is less well established. A study was developed to evaluate the feasibility of implementing PROM in routine outpatient care across diverse cultural contexts in Asia. Methods: PROMiSE-Pilot is a prospective, multi-centre, feasibility study of integrating PROM in routine outpatient care across Asia. The Edmonton Symptom Assessment Scale questionnaire (ESAS-r) was selected as the PROM tool. Clinicians in 4 hospitals in Singapore, Manila, Bangkok and Hyderabad will be invited to participate, and their patients will be invited to complete the ESAS-r on paper before each visit. The primary aim is to evaluate if proportion of patients who complete ≥5 of 10 items on ESAS-r is ≥85% (Clopper Pearson). Secondary aims include assessing proportion who complete ≥8 and all 10 items and perceived utility of ESAS-r evaluated through surveys adapted to measure patient and clinician satisfaction. Site-specific patient, clinician, administrative barriers and facilitators will be studied. A pragmatic approach to context-specific implementation was adopted with each site developing its own process map for delivering the pilot and adapting to local patient demographics (e.g. low literacy), cultural contexts and resources. Translated versions of ESAS-r were acquired where necessary. Recruitment commenced in March 2024 following ethics approval at 2 sites. 87 patient encounters have been captured from 5 participating clinicians in Singapore. 5 clinicians have agreed to participate in Bangkok. Target recruitment is 200 encounters per site. Multi-centre data will be presented at the Breakthrough congress. Clinicians from ASCO LDP-AP identified PROM as a low-cost but potentially high-value approach to improving quality of care in resource limited settings in Asia. Understanding the feasibility of such a tool is vital prior to consideration of wider scale adoption by stakeholders. This co-developed multi-national pilot additionally demonstrates the value of collaboration, our strength in diversity and a pragmatic model for investigator-initiated studies in Asia.
CORRECT-MRD I: A clinical validation study to predict recurrence in stage II-III colorectal cancer (CRC) using a bespoke circulating tumor DNA (ctDNA) assay to detect molecular residual disease (MRD).
Authors: Tsukada Yuichiro , Sagawa Tamotsu , Srinivasan Gopalakrishnan , Hubert Ayala , Purim Ofer , Semenisty Valeriya , Lo Nangi , Mondello Giuseppe , Cubillo Gracian Antonio , Marti Tara , Subramaniam Somasundaram , Palomares Melanie R. , Baehner Frederick , de Jong Floris A , Kerr David James , Yoshino Takayuki
Published: August 2024

TPS98

Background: Despite standard of care management with surgery ± adjuvant chemotherapy treatment (ACT), >30% of patients (pts) with resectable CRC recur. The presence of ctDNA in plasma after resection and after ACT, has been shown to be a strong prognostic factor for the risk of recurrence, suggesting that the presence of ctDNA in blood is molecular evidence of residual disease. As such, ctDNA analysis may enable post-surgical risk stratification for ACT decision-making, as well as detection of molecular recurrence during surveillance and subsequent early intervention. The CORRECT-I study aims to validate the association of post-definitive therapy and pre-recurrence follow-up ctDNA positivity with recurrence-free interval (RFI) in pts who have undergone complete surgical resection for stage II or III CRC. Methods: This study is a prospective, observational, multicenter study, which is open in Israel, Italy, Japan, Spain, and the UK. Pts must have pathologically confirmed stage II or III CRC, have undergone complete surgical resection, and have tissue available from the primary resection. Pts may not have started ACT prior to baseline blood draw post-surgery. Pts are asked to provide serial whole blood specimens for ctDNA analysis at a) post-surgical baseline, b) pre-recurrence follow-up visits (max 15 blood draws over max 5 years), and c) clinical recurrence. ctDNA will be analyzed with an NGS-based tumor-informed MRD assay that identifies somatic genomic alterations from DNA derived from the patient’s tumor tissue and detects a selected subset of tumor-specific (bespoke) ctDNA in their blood. The primary objective of this study is to validate the association of post-definitive therapy and serial pre-recurrence follow-up ctDNA positivity with RFI, using a Cox proportional hazards regression analysis. Further objectives include the assessment of sensitivity and specificity of the ctDNA assay, the association between ctDNA at individual timepoints and RFI, ctDNA dynamics and RFI, and the time from ctDNA positivity to clinical recurrence. A multivariable model, including ctDNA, clinicopathological risk features, serial serum CEA assessments, and recurrence risk as determined by the Oncotype Colon Recurrence Score will be fit with RFI as endpoint. The primary analysis will be conducted when ≥30 histologic and/or radiographic confirmed cases of clinical recurrence have been observed. As of April 2, 2024, 158 pts of 400 have been enrolled.
Spontaneous emergence of temporal structures in a continuously driven many-body system
Authors: Li Tingmei , Li Hong-Xia , Chen Yu-Hui , Zhang Xiangdong
Published: August 2024

The spontaneous emergence of temporal structures challenges the conventional understanding that systems governed by time-invariant laws remain unchanged over time. Recent experiments have observed this time translation symmetry breaking in quantum atomic systems that either exhibit strong atom-atom interactions or have low dissipation rates. While current theoretical frameworks reveal the importance of strong atom-atom interactions, they fall short in explaining this phenomenon observed in low-dissipation atomic systems. Here, we present a theoretical study on the spontaneous breaking of time translation symmetry in materials with low dissipation rates. By constructing phase diagrams for a system of four-level atoms driven by a continuous-wave optical field, we identify the essential requirements for self-sustained temporal motions. These include a driven open system, nonlinear interactions, and sufficient degrees of freedom that facilitate competing processes. Our findings contribute to a better understanding of the emergence of spontaneous time translation symmetry breaking in these materials.
Passerine birds supporting cross pollination in Erythrina stricta Roxb.
Authors: Khanduri Vinod Prasad , Kumar Kewat Sanjay , Sharma Chandra Mohan , Riyal Manoj Kumar , Kar Kalpataru , Singh Bhupendra , Sukumaran Arun
Published: August 2024

Erythina stricta is an ecologically important tree species in the rainforests of India and its nectar within the flowers contributes to birds’ diet and survival. Reports on the pollination of this species have not been published so far. We therefore explore the reproductive system of this tree species which has great significance to its ecosystem. Birds have an important role in the reproduction of trees through pollination particularly in tropical areas where reproductive success mostly depends on animal pollinator interactions. Study of visitation and nectar feeding behaviour of birds along with breeding system assessment of Erythina stricta. Birds visiting and foraging behaviour was observed during Erythrina stricta flowering season in an indian tropical rainforest. Reproductive system was assessed through controlled pollination experiments. Thirteen bird species were recorded visiting and foraging nectar from the flowers of Erythrina stricta. The maximum numbers of visits recorded were from the Red-vented Bulbul (Pycnonotus cafer, Pycnonotidae). The nectar feeding birds were, either (i) potential pollinator with long bills (e.g. Pycnonotus spp., Chloropsis aurifrons, and Dicrurus spp.) or (ii) nectar robbers with comparatively shorter bills (e.g. Zosterops palpebrosa, Stachyris ruficeps, Macronous gularis, Heterophasia glaciris). Controlled pollination experiments revealed high degree of cross pollination (xenogamy) and self-incompatibility in E. stricta. Birds were more frequent in early mornings and their foraging activity was also observed during evening hours; the frequency however, declined with respect to nectar availability. Long corolla tubes of E. stricta could restrict access to nectar collecting bees.
Ο ρόλος των νευροτροφίνων NGF και BDNF στις γυναίκες με υπερδραστήρια κύστη και η συσχέτιση των επιπέδων τους με την κλινική εικόνα και την αποτελεσματικότητα της φαρμακευτικής θεραπείας
Authors: Μπέτα Αναστασία
Published: August 2024

Εισαγωγή-Σκοπός: Το Σύνδρομο Υπερδραστήριας Κύστης (Overactive Bladder Syndrome – OAB), είναι μία κατάσταση με επίπτωση 16.9% η οποία επηρεάζει σε μεγάλο βαθμό την ποιότητα ζωής των ασθενών. Μέχρι τώρα, η διάγνωση του συνδρόμου καθώς και η εκτίμηση της αποτελεσματικότητας των θεραπευτικών μεθόδων, βασίζονται κυρίως σε υποκειμενικά δεδομένα. Σκοπός της παρούσας μελέτης ήταν η αξιολόγηση του ρόλου των νευροτροφινών NGF (Nerve Growth Factor) και BDNF (Brain Derive Neurotrophic Factor) στα ούρα, σε ασθενείς με OAB που υποβάλλονται σε θεραπεία με Μιραβεγρόνη, έναν β3-αδρενεργικό αγωνιστή, ως πιθανοί βιοδείκτες για την ενίσχυση της διάγνωσης της OAB και της εκτίμησης της αποτελεσματικότητας της θεραπείας. Υλικό – Μέθοδος: Στη μελέτη συμπεριλήφθηκαν 30 ασθενείς όπου ετέθη η διάγνωση της OAB βάσει του ορισμού από την ICS (International Continence Society) και 15 υγιείς μάρτυρες. Ο προσδιορισμός των επιπέδων των νευροτροφινών στα ούρα έγινε σε δείγματα που συλλέχθηκαν κατά την έναρξη της μελέτης (για τις ασθενείς και τις μάρτυρες) και 3 μήνες μετά τη χορήγηση Μιραβεγρόνης (στην ομάδα των ασθενών). Ο προσδιορισμός έγινε με την ανοσοενζυμική μέθοδο ELISA (Εnzyme Linked Immunosorbent Assay) και ακολούθησε περαιτέρω ομαλοποίηση των τιμών με την κρεατινίνη ούρων. Η εκτίμηση της αποτελεσματικότητας της θεραπείας έγινε με τη σύγκριση των απαντήσεων στο ερωτηματολόγιο IUSS (Indevus Urgency Severity Scale).Αποτελέσματα: Τα επίπεδα NGF/Cre και BDNF/Cre στα ούρα ήταν σημαντικά υψηλότερα στις ασθενείς με OAB σε σχέση με τις μάρτυρες (p<0,001 και p=0,03 αντίστοιχα). Επιπλέον, τα επίπεδα του NGF/Cre και του BDNF/Cre μειώθηκαν στατιστικά σημαντικά μετά τη θεραπεία με Μιραβεγρόνη στο σύνολο των ασθενών (p<0,001 και p=0,005 αντίστοιχα), όμως η μείωση στην υποομάδα των γυναικών που δεν ανταποκρίθηκαν στην θεραπεία, δεν ήταν στατιστικά σημαντική (p=0.052 για τον NGF/Cre και p=0.878 για τον BDNF/Cre). Οι ασθενείς που ανταποκρίθηκαν στη θεραπεία παρουσίασαν χαμηλότερα επίπεδα NGF/Cre 3 μήνες μετά τη θεραπεία σε σύγκριση με εκείνες που δεν ανταποκρίθηκαν (ρ=0,05). Συμπεράσματα: Οι ασθενείς με OAB παρουσιάζουν αυξημένα επίπεδα NGF και BDNF στα ούρα, με τα επίπεδα αυτά να μειώνονται μετά τη θεραπεία. Έτσι φαίνεται ότι μπορεί να παίζουν σημαντικό ρόλο στην ανάπτυξη των συμπτωμάτων της υπερδραστηριότητας της ουροδόχου κύστης και αναδύονται ως πιθανοί βιοδείκτες για την αξιολόγηση των θεραπευτικών αποτελεσμάτων. Η χρήση των μετρήσεων των NGF και BDNF στα ούρα για τη διάγνωση και την αξιολόγηση της θεραπείας της OAB θα μπορούσε να αποτελέσει ένα πιο αντικειμενικό εργαλείο από τα υπάρχοντα μέτρα που βασίζονται σε αναφορές ασθενών. Επιπλέον, η κατανόηση του ρόλου τους μπορεί να προσφέρει πληροφορίες σχετικά με την παθοφυσιολογία του συνδρόμου και να συμβάλει σε πιο στοχευμένες θεραπείες στο μέλλον.
The genome sequence of the northern pintail, Anas acuta Linnaeus, 1758
Authors: O’Brien Michelle F. , Lopez Colom Rosa ,   Natural History Museum Genome Acquisition Lab,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: August 2024

We present a genome assembly from an individual female Anas acuta (the northern pintail; Chordata; Aves; Anseriformes; Anatidae). The genome sequence spans 1,189.30 megabases. Most of the assembly is scaffolded into 39 chromosomal pseudomolecules, including the W and Z sex chromosomes. The mitochondrial genome has also been assembled and is 16.6 kilobases in length.
The genome sequence of the Small Scabious Mining Bee, Andrena marginata Fabricius, 1776
Authors: Mitchell Ryan , Monks Joseph ,   Natural History Museum Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: August 2024

We present a genome assembly from an individual female Andrena marginata (the Small Scabious Mining Bee; Arthropoda; Insecta; Hymenoptera; Andrenidae). The genome sequence spans 373.60 megabases. Most of the assembly is scaffolded into 6 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 21.16 kilobases in length.
The genome sequence of the yellow mealworm beetle, Tenebrio molitor Linnaeus, 1758
Authors: Mann Darren , Crowley Liam M. , Merino Recalde Nilo ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: August 2024

We present a genome assembly from a male yellow mealworm Tenebrio molitor larva (Arthropoda; Insecta; Coleoptera; Tenebrionidae). The genome sequence has a total length of 277.00 megabases. Most of the assembly is scaffolded into 11 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 15.78 kilobases in length.
The genome sequence of the acalyptrate fly Dryomyza anilis Fallén, 1820
Authors: Sivell Olga , Sivell Duncan , Webb Judith A. , Mitchell Ryan , Ashworth Michael ,   Natural History Museum Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: August 2024

We present a genome assembly from an individual male acalyptrate fly Dryomyza anilis (Arthropoda; Insecta; Diptera; Dryomyzidae). The genome sequence has a total length of 656.60 megabases. Most of the assembly is scaffolded into 7 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 16.48 kilobases in length.
The genome sequence of an elaterid beetle, Ctenicera cuprea (Fabricius, 1775)
Authors: Hislop Louise ,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: August 2024

We present a genome assembly from an individual male elaterid beetle, Ctenicera cuprea (Arthropoda; Insecta; Coleoptera; Elateridae). The genome sequence spans 647.70 megabases. Most of the assembly is scaffolded into 12 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 17.58 kilobases in length. Gene annotation of this assembly on Ensembl identified 15,524 protein-coding genes.
EVALUATION OF VARIETIES OF SPRING SOFT WHEAT BY GRAIN QUALITY INDICATORS IN THE CHANGING CONDITIONS OF THE MIDDLE VOLGA REGION
Authors: Taranova Tat'yana , Romenskaya Svetlana , Demina Elena , Kincharov Alexander
Published: August 2024

The research was conducted in 2019-2021 in the forest-steppe zone of Samara region. The purpose of the research is to screen samples of the world collection of spring soft wheat according to grain quality indicators in the conditions of the Middle Volga region to identify sources valuable for breeding. The soil of the site is typical low-humus medium-sized light clay chernozem. Meteorological conditions differed by years and from the long-term norm, but were generally characterized as arid. The hydrothermal humidification coefficient was 0.48 in 2019, 0.52 in 2020, 0.39 in 2021, and 0.73 for many years. The object of research is 130 samples of different ecological and geographical origin, single repetition, standard - zoned variety Tulaykovskaya Nadezhda. Grain quality indicators were evaluated according to the methodology of the State Commission for Variety Testing and the current National standards of the Russian Federation. According to the results of the research, varieties of spring soft wheat with high values of quality indicators were identified. According to physical properties – grain nature (831...864 g/l) and vitreousness (80...89 %), the following varieties were distinguished: Kinelskaya Niva, Kinelskaya Yubileynaya, Kinelskaya 2020 (Kinel), Tulaykovskaya 116, Ekada 113 (Bezenchuk), Burlak, Ulyanovskaya 105 (Ulyanovsk), Saratovskaya 73, Saratovskaya 74, Liniya 666, Albidum 28 (Saratov), Orenburgskaya 23 (Orenburg), Stepnaya Volna (Altai region). The samples exceeded the standard by 1...34 g/l and 1...10%, respectively. According to technological properties, high protein content (17.40...20.56%) and gluten (40.13...49.26 %) were noted varietals: Kinelskaya 59, Erythrospermum 5289 (Kinel), Sibirskiy Alyans, Stepnaya Niva (Altai region), Novosibirskaya 15, Novosibirskaya 31, Novosibirskaya 41, Polyushko (Novosibirsk), Omskaya 37, Omskaya 38, OmGAU 100, Sigma (Omsk), Balkysh (Tatarstan), Nikon (Ulyanovsk), Gunner (Canada), Long Fu 13 (China), Digana (Switzerland). The excess over the standard was 1.88...5.04% and 4.13...13.26%, respectively. The selected cultivars are recommended to be used in the breeding process as parent forms to create varieties with high grain quality indicators.
GRASS MIXTURES FOR THE CREATION OF HIGH-QUALITY INTENSIVE HAYMAKING IN THE SEMI-DESERT ZONE OF RUSSIA
Authors: Tyutyuma Natalia , Egorova Galina , Kudryashova Natal'ya
Published: August 2024

The purpose of the study is to improve the species composition of grass mixtures under irrigated conditions to increase their productivity, longevity and provide livestock with high-quality feed. The experiments were performed in 2019-2022 on old plowed lands located in the right-bank steppe of the north of Astrakhan region under irrigation. Irrigation method: sprinkling, 10 vegetation irrigations per season. The soil is light chestnut, medium loamy with a humus content of 0.90...1.00%. mobile phosphorus and potassium (according to Machigin) – 69 and 361.5 mg/kg, respectively. We studied 6 variants of grass mixtures: control (creeping wheatgrass, angustifolia bluegrass, awnless brome, coastal sedge, swamp grass, California cocklebur); grass mixture 1 – 25:25:25:25% (blue hybrid alfalfa, meadow clover, meadow timothy, meadow fescue; grass mixture 2 – 30:40:30% (meadow clover, multi-cut ryegrass, meadow fescue; grass mixture 3 – 50:50% ; (meadow clover and reed grass); grass mixture 4 – 25:25:25:25% (eastern goat’s rue, meadow clover, multi-cut ryegrass, meadow fescue; grass mixture 5 – 25:25:25:25% (meadow clover, meadow timothy) , multi-cut ryegrass, common beckmania); grass mixture 6 – 50:25:25% (meadow clover, festulolium, intermediate wheatgrass. The most productive were grass mixtures No. 1 and No. 2 – 147.6 and 156.3 t/ha of green mass, which higher than the control by 134.3 and 143.0 t/ha, respectively. All studied options were distinguished by high nutritional value - the content of feed units per 1 kg of dry biomass varied from 0.75 kg per 1 kg of feed for grass mixture No. 2 to 0.85. kg per 1 kg of feed for grass mixture No. 5. When feeding all grass mixtures with hay, the animals had a higher average daily weight gain (1.2...1.7 higher) in terms of nutritional value, compared to feeding with hay from natural grass. The high productivity and price of hay of legume-grass grass mixtures determine the high profitability (177%) of its production, which is 3.3 times higher than natural haymaking.
Correlation between muscle tissue and type 2 diabetes
Authors: Noga Rafal , Marcinkowska Jagoda , Miśkiewicz Marek , Ptak Jakub , Herc Adrian , Sawczuk Marcelina , Koczkodon Karolina , Teska Victoria , Perłowski Jakub , Krompiewski Mariusz
Published: August 2024

Diabetes is one of the most common diseases in the world. There are several types of it with different etiologies. The most common type of diabetes is type 2. Every year, DM2 contributes to the deaths of millions of people worldwide. Its complications pose a huge health as well as economic problem. Nowadays, pharmaceutical companies are outdoing themselves in synthesizing new drugs, using newer and newer mechanisms of action. This meets with the approval of patients – It is easier to take a pill instead of changing your lifestyle. However, it is worth considering and rethinking the pathophysiology of type 2 diabetes. How to effectively reduce the risk of pre-diabetes or developing DM2? In this research study, we will try to give an insight into how important our body's muscle tissue is in the context of diabetes and why it is important to take care of its proper amount and condition. It is hoped that paying attention to this aspect in relation to diabetes will allow for a less invasive and more effective treatment of carbohydrate disorders and contribute to benefiting from the other health effects of developing proper skeletal muscle tissue in the human body.
Comprehensive Insights into Neuropsychiatric Systemic Lupus Erythematosus
Authors: Turek Monika , Wojciechowska Klara , Piątkowska Karolina , Jaroń Aleksandra , Jastrzębska Katarzyna , Chaberska Iwona , Feruś Aleksandra , Lipska Julia
Published: August 2024

Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, often affecting women of childbearing age, with periods of exacerbations and remissions. SLE can impact multiple organs, causing a range of clinical symptoms. Neuropsychiatric systemic lupus erythematosus (NPSLE) includes symptoms like headaches, seizures, anxiety disorders, cognitive dysfunctions, psychosis, and neuropathies. Its diagnosis is challenging, and treatment is complex.
Purpose: This study aims to explain the pathophysiology of NPSLE, describe diagnostic methods, and summarize current treatment methods based on recent research.
Methods: Databases such as PubMed, Medline, and ResearchGate were used.
State of current knowledge: Early and accurate diagnosis of SLE is crucial for optimal patient management. The 2019 EULAR/ACR classification criteria have improved diagnostic precision with a weighted scoring system for diverse disease manifestations. Therapy of neuropsychiatric lupus focuses on symptom control and causal treatment, considering anti-inflammatory action or counteracting ischemic incidents. It involves immunosuppressive agents and antiplatelet or anticoagulant substances. Non-pharmacological interventions and lifestyle modifications are also important. The dynamic criteria reflect ongoing advancements in understanding SLE, emphasizing continuous research and collaboration.
Conclusions: The diagnosis of NPSLE requires excluding other causes of neuropsychiatric symptoms, such as infections, endocrine disorders, or drug reactions. Diagnostic methods vary based on symptoms, including lumbar puncture, CSF analysis, EEG, cognitive function assessment, and MRI. The treatment of NPSLE focuses on symptom control and causal treatment, with therapy individualized based on symptom severity and patient burden.
Health problems among women in sports: The Female Athlete Triad
Authors: Karkos Patrycja , Kuśmierczyk Katarzyna , Jurga Marta , Jurga Kacper , Grodziński Bartłomiej , Sztemberg Elena , Gruszczyńska Hanna , Grzelka Michalina , Głoskowska Julia , Kuleta Katarzyna
Published: August 2024

Introduction:Over the years the participation of women in sports and physical activities has significantly increased. The rise in the number of female athletes has brought to attention the health issues specific to this population. The Female Athlete Triad is a syndrome in which the affected woman presents the combination of three intertwined conditions such as (1) low energy availability, (2) menstrual dysfunction, and (3) low bone mineral density. The crucial factor in the pathophysiology is energy imbalance, which leads to impairment of the reproductive and skeletal system, eventually having a very harmful effect on the whole organism and leading to appalling short-term and long-term consequences. It affects women of all ages and from every sports discipline, but most at risk are those in adolescence involved in sports that prioritize leanness and endurance.
Purpose:The objective of this article is to review the current state of knowledge about the Female Athlete Triad, spreading awareness of this syndrome, which is still very low in society, and highlighting the importance of early identification and multidisciplinary treatment to prevent serious complications.
Materials and methods: The review was based on a comprehensive analysis of the available literature sourced from PubMed, Google Scholar, and other scientific articles, which was searched by using listed keywords and analysed for topic relevance and knowledge currency.
Gut microbiota and rheumatic diseases: new insights into pathogenesis
Authors: Pażyra Aldona , Nowakowska Katarzyna , Więsyk Piotr , Oklecińska Łucja
Published: August 2024

Background: Rheumatic diseases are a group of disorders characterised by a loss of immune tolerance, which leads to chronic inflammation, degeneration or metabolic abnormalities in various organs or tissues. Despite the lack of clarity surrounding the causes of these diseases, both environmental and genetic factors play an important role. Recent research indicates that alterations in the composition of the gut microbiota, known as gut dysbiosis, may contribute to the development of a number of rheumatic diseases, including rheumatoid arthritis, systemic lupus, ankylosing spondylitis, systemic scleroderma and Sjögren's syndrome. The gut microbiota influences the balance between pro- and anti-inflammatory immune responses, which may have important implications for the pathogenesis of these diseases. Furthermore, studies have indicated that the composition of the gut microbiota may be associated with the response to therapies used to treat rheumatic diseases, thus opening up new avenues for the development of microbiota-targeted treatments for these conditions. Aim of the study: The objective of this review is to investigate the impact of the gut microbiota on the pathogenesis of rheumatic diseases and to evaluate potential therapies targeting the manipulation of the gut microbiota. Material and methods: The present study is based on literature available in scientific databases from 2019-2024, such as PubMed, Corchane Library and Google Scholar.Results and conclusions: A growing body of evidence suggests a potential link between the gut microbiota and rheumatic diseases. Patients often exhibit a reduced ratio of Firmicutes to Bacteroidetes and abnormal numbers of Bacteroides. Molecular mimicry and a potential association with short-chain fatty acids have also been observed. Further human studies are needed to more fully understand the role of the gut microbiota and potential therapeutic interventions.
Code and Data Repository for Exact and Approximation Algorithms for Sparse Principal Component Analysis
Authors: Li Yongchun , Xie Weijun
Published: August 2024

Sparse principal component analysis (SPCA) is designed to enhance the interpretability of traditional principal component analysis by optimally selecting a subset of features that comprise the first principal component. Given the NP-hard nature of SPCA, most current approaches resort to approximate solutions, typically achieved through tractable semidefinite programs or heuristic methods. To solve SPCA to optimality, we propose two exact mixed-integer semidefinite programs (MISDPs) and an arbitrarily equivalent mixed-integer linear program. The MISDPs allow us to design an effective branch-and-cut algorithm with closed-form cuts that do not need to solve dual problems. For the proposed mixed-integer formulations, we further derive the theoretical optimality gaps of their continuous relaxations. Besides, we apply the greedy and local search algorithms to solving SPCA and derive their first-known approximation ratios. Our numerical experiments reveal that the exact methods we developed can efficiently find optimal solutions for data sets containing hundreds of features. Furthermore, our approximation algorithms demonstrate both scalability and near-optimal performance when benchmarked on larger data sets, specifically those with thousands of features.
Play in peril: charting the decline of playgrounds across 40 years
Authors: Wheway Rob
Published: August 2024

Author of a landmark directory of adventure and holiday play provision in 1980 draws on new data that documents how many schemes are still running and assesses the impact that closures have had on children
Jonathan Hall KC
Authors: Warren-Lister Megan
Published: August 2024

Megan Warren-Lister speaks to the government's terrorism legislation adviser
Transition from care
Authors: Wilson Danny
Published: August 2024

Councils need to develop a more flexible leaving care process, says Danny Wilson, head of children's residential at Bedspace
Tackling family court delays
Authors: Oldershaw Richard
Published: August 2024

Children's welfare is being harmed by ongoing backlogs in the family court process which need to be addressed urgently says Richard Oldershaw, senior legal adviser at Coram's Child Law Advice Service
Breaking barriers to employment and education
Authors: Józwiak Gabriella
Published: August 2024

Coaching scheme gives young participants the tools they need to make positive changes, overcome life's challenges and get back into work or learning
Innovative therapies for hair restoration and rejuvenation: an overview
Authors: Ramadan Francesa
Published: August 2024

Hair loss and baldness are incredibly common conditions with a significant negative impact on a person's psychosocial functioning and quality of life. Only two drug treatments are currently available for the treatment of hair loss, but side effects render their usage limited. Substantial advancements in hair restoration and rejuvenation in aesthetic medicine have been achieved, particularly in non-surgical treatment options. Francesca Ramadan supplies an overview of some of the options most commonly offered in aesthetics clinics.
Maximising AI in Manufacturing
Authors: Royles Chris
Published: August 2024

As manufacturers look at how to maximise and optimise their use of AI, could the answer lie in asking AI how to do it?
Supplemental table for "Prediction of Chlorophyll-a as an Index of Harmful Algal Blooms Using Machine Learning Models"
Authors: Busari Ibrahim , Sahoo Debabrata , Harmel Daren , Haggard Brian
E.
Published: August 2024

The study involves prediction of chlorophyll-a as HABs index using different machine learning models.
Risk Factors for Pulmonary Mycosis in Immunocompromised Patients in Surakarta, Indonesia
Authors: Nugratama Kevin Aditya , Raharjo A. Farih , Mashuri Yusuf Ari
Published: August 2024

Introduction: Recent evidence shows that there is an increase in the incidence of pulmonary mycosis globally. In clinical settings, pulmonary mycosis is commonly misdiagnosed as pulmonary tuberculosis (PTB). Identifying risk factors can ease the diagnosis of pulmonary mycosis. This study aimed to determine the risk factors for pulmonary mycosis in immunocompromised patients in Surakarta.

Methods: This was an analytic observational study with a retrospective cohort study method. This study used purposive sampling technique on 218 medical records of immunocompromised patients during January 2019–September 2022 at a referral hospital in Surakarta. The correlation of sociodemographic, health status, health behavior, history of diseases, medications, and transplantations with the incidence of pulmonary mycosis was analyzed using Chi-Square test or Fisher’s exact test as its alternative.

Results: There was a significant correlation between educational level (p=0.018), nutritional status (p=0.001), smoking habit (p=0.000), history of corticosteroid use (p=0.031), history of antibiotic use (p=0.006), history of chemotherapy (p=0.003), history of PTB (p=0.047), and history of chronic obstructive pulmonary disease (COPD) (p=0.001) with the incidence of pulmonary mycosis. Meanwhile, there was no significant correlation between occupation (p=0.057), neutrophil level (p=1.000), history of human immunodeficiency virus (HIV) infection (p=1.000), history of diabetes mellitus (DM) (p=0.070), and history of organ transplantation (p=1.000) with the incidence of pulmonary mycosis.
Conclusion: Low educational level, malnutrition, smoking habit, history of pulmonary diseases, and medications are the risk factors for pulmonary mycosis in immunocompromised patients in Surakarta. It is important to identify these risk factors when examining patients with respiratory disorder symptoms.
Photon-counting phase-stabilized dual-comb ranging
Authors: Liu Yingyu , Zhong Wei , Wang Chong , Zhao Ruocan , Chen Tingdi , Fang Jiajie , Han Fei , Xue Xianghui
Published: August 2024

Dual-comb ranging (DCR), with its superior overall performance compared to traditional ranging technologies, has recently attracted widespread interest in the research community. Nevertheless, the ranging distance or the material of the targets is limited by the detection sensitivity of optical asynchronous linear sampling. This limitation restricts the application of DCR in several highly significant scenarios. Here, we utilize the photon-counting method to dramatically break through the detection sensitivity to femtowatt. To overcome the impact of fiber-length wandering and achieve Michelson interference based absolute distance measurement, an orthogonal polarization interferometry-arm configuration and a reference-arm based photon-counting trigger protocol are proposed. This photon-counting DCR system can conduct long-period photon-counting coherently, thus, realizing the lowest detection power of phase-stabled DCR to date. The results show that with only 18 femtowatt average power detected, the time-of-flight and multi-wavelength interferometry yields a precision of 22 µm and 8 nm in 3 min, respectively. This work paves the way for the field of large-scale spacecraft formation flying, synthetic aperture space telescope position attitude control, interplanetary positioning, and hard target distance measurement.