bluuebunny/crossref_metadata_2025 huggingface dataset:
Revealing the crucial roles of myxoma cells and CD206+ macrophages in cardiac myxoma progression based on single-cell sequencing.
Authors: Jiang Zedong , Kang Qianlong , Tong Huan , Li Guangqi , Ma Xuelei
Published: June 2024

e23549

Background: Cardiac myxoma is a commonly encountered tumor within the heart that has the potential to be life-threatening. However, the cellular composition and molecular characteristics of this condition are still not well understood. Methods: We performed single-cell sequencing on cardiac myxoma tissues obtained from 5 patients, focusing on the identification and characterization of cellular subtypes, cell trajectory analysis, and intercellular communication analysis. We performed a comparative analysis of the changes in cell types and states between cardiac myxoma and normal heart tissues. Furthermore, we retrospectively collected pathological sections from 49 cardiac myxoma cases and employed the multi-color immunohistochemistry (mIHC) technology to analyze the relationship between cellular infiltration and the severity of disease. Results: In total, 75,641 cells in cardiac myxoma tissues formed 9 distinct cell populations. Myxoma cells exhibited a significant resemblance to fibroblasts, yet they were distinguished by an increased expression of phosphodiesterases and genes associated with cell proliferation, differentiation, adhesion, and migration. Myxoma cells displayed cellular heterogeneity and demonstrated two distinct evolutionary pathways. One involves the transition from stem cell-like cells to stromal cells and the other involves enhancement of blood coagulation function. Immune cells surrounding the myxoma displayed suppressive features, with the presence of CD8+ T cells expressing TOX and GZMK, as well as a decrease in the secretion of cytotoxic molecules, indicating an impaired effector function. Macrophages were found to express growth factors such as EREG and PDGFC which played a role in promoting myxoma growth. Conversely, myxoma cells were also observed to secrete ANGPTL4 and ANXA1 which in turn induced the transformation of CD206+ macrophages. Extensive mIHC experiments indicated that a higher proportion of CD206+macrophages and myxoma cells infiltrating the myxoma tissues, along with their enhanced spatial interaction, were found to significantly contribute to the increased occurrence of embolism in cardiac myxoma patients. Conclusions: In summary, this study presents a comprehensive single-cell atlas of cardiac myxoma, highlighting the heterogeneity of myxoma cells and their collaborative impact on immune cells. These findings shed light on the complex pathobiology of cardiac myxoma and present potential targets for intervention.
Association of mutational status with metastatic pattern, race, ethnicity, and overall survival (OS) in leiomyosarcoma (LMS).
Authors: Pearce Hayes , Yu-Cherng Chang , Rose Brandon Edward , Jonczak Emily E. , Grossman Julie , D'Amato Gina Z. , Huang Marilyn , Trent Jonathan C. , Alessandrino Francesco
Published: June 2024

e23553

Background: LMS, one of the most common soft tissue sarcomas, can arise from the uterus, retroperitoneum, vessels, or extremities. It is unclear if the metastatic pattern and potentially the mutational status differs among the different types of LMS. We investigated the association between sites of metastases, mutations, race, ethnicity, and OS in different LMS types. Methods: This single-center retrospective study evaluated patients with biopsy-proven LMS that underwent genomic testing between January 2009 and May 2023. Association between genomic profile, sites of metastases, types of LMS (extremity, retroperitoneal, uterine, vascular), self-reported race and ethnicity was performed using Fisher’s exact test. Survival curves for self-reported race and ethnicity, mutations, sites of metastases, and types of LMS were estimated using the Kaplan-Meier method and compared with a log-rank test. Cox proportional hazard regression models were used to examine the association between OS with types of LMS, self-reported race and ethnicity, mutational status, and sites of metastases. Results: The study included 110 subjects (F/M:81/29; median age 57 years, 99/110 with metastatic disease). 27/110 (25%) subjects self-reported as Hispanic, and 27/110 (25%) as Black. The most common type of LMS was uterine (50/110, 45%), followed by retroperitoneal (27/110, 25%), extremities (23/110, 21%) and vascular (10/110, 9%). The most common mutation was TP53 (74/110, 67%), followed by RB1 (24/110, 22%). ER/PR expression was present in 25/110 subjects (23%). The lungs were the most common site of metastasis (79/99, 80%), followed by the liver (37/99, 37%), and pelvis (29/99, 29%). Peritoneal and pelvic metastases were more common in uterine LMS (p = 0.0001 and 0.002, respectively). Liver metastases were more common in retroperitoneal LMS (p = 0.03). TP53 mutation was more common in vascular LMS (p = 0.03), whereas intermediate/high tumor burden was more common in LMS arising from the extremities (p = 0.004). BRCA1/2 mutations were more common in subjects with liver (p = 0.02) and intramuscular metastases (p = 0.04). Pleural metastases (11/99, 11%) were associated with lower OS (Risk Ratio: 2.7; 95% CI: 1.13, 6.32; p = 0.02). ATRX mutation (17/110, 15%) was more common in Hispanic subjects (p = 0.005), in which it was associated with lower OS (p = 0.0007). Conclusions: The mutational status and metastatic pattern of LMS varies based on the LMS types, and potentially provides prognostic data. In our sample, OS was reduced in Hispanic subjects with ATRX mutation, and the presence of pleural metastases was also independently associated with shorter OS.
Assessing response and adherence to neoadjuvant treatment in soft tissue sarcomas of the extremities.
Authors: Alamilla-Garcia Gabriela , Williams Haydée , Garcia-Ortega Dorian Yarih
Published: June 2024

e23559

Background: The standard treatment for large, intermediate, and high-grade extremity soft tissue sarcoma (ESTS) involves surgery and radiotherapy. The addition of chemotherapy has improved oncological outcomes, such as reduced recurrence and prolonged survival. However, the relationship between neoadjuvant treatment and tumor response in ESTS is not well understood. Pathological evaluation of viable tumor cells after treatment is an indicator of tumor response, yet the proportion of viable tumor cells remains high, particularly in high-risk sarcomas. Combining radiotherapy with chemotherapy may enhance the response of tumor cells. Objective: This study aims to evaluate the effects of neoadjuvant chemotherapy (NCT) and chemoradiotherapy (CRT) on patients with high-risk ESTS and to determine its impact on the pathological response. Methods: We enrolled adult patients with high-risk ESTS (SARCULATOR OS < 60%) at a single center in Latin America. The study was designed to analyze the pathological response in patients with high-risk sarcomas who underwent neoadjuvant CRT and resection and to correlate these responses with various variables. The treatment response was evaluated using the EORTC–STBSG criteria. Results: Thirty-four patients were recruited, with a median age of 44 years (IQR 23-74). Fifty-two percent had T3 tumors (mean size 18 cm), and 79.4% were diagnosed at stage III. The predominant histological subtypes were synovial sarcoma (35.3%) and dedifferentiated liposarcoma (29.4%). The most used NCT regimen was doxorubicin/ifosfamide (84.4%), with 62.5% receiving a dosage intensity of Q4W, affected by overcapacity, and 25% received Q3W. Concurrent CRT was administered to 64.7% of patients, with a median delay to onset of 36 days due to overcapacity (43.5%). Only 79.4% completed three preoperative cycles of treatment. As for the response, 41.2% had an EORTC-E response, and 17.6% had an EORTC-D response. Grade 3 neutropenia and anemia occurred in 17.2% and 8.8% of patients, respectively. Disease progression during NCT was observed in six patients. No significant difference was found in the pathological response between the Q4W and Q3W dosage intensities (p = 0.62). Conclusions: The impact of NCT on pathological responses was not significantly high, which may be due to the predominant histological type in our series. The main cause of treatment delay at our center was due to overcapacity; however, this did not influence the pathological response relative to dose intensity. Additional follow-up assessments are required to determine the influence on relapse-free and overall survival based on the response after preoperative CRT.
Update on GALLANT: A phase 2 study using metronomic gemcitabine, doxorubicin, and docetaxel plus nivolumab in previously treated sarcoma (NCT04535713).
Authors: Omelchenko Nadezhda , Chawla Sant P. , Agarwal Anmol Dia , Jeffrey Samantha , Sena Cota Luisa , Chua Victoria , Moradkhani Ania , Quon Doris V. , Wong Steven , Gordon Erlinda Maria
Published: June 2024

e23569

Background: Metronomic dosing of gemcitabine, doxorubicin and docetaxel causes less severe side effects than standard chemotherapy for advanced sarcoma. Hypothesis: The addition of nivolumab to this regimen will have synergistic effects and improve treatment outcomes. Objectives: Primary objective: To assess progression-free survival (PFS); Secondary objectives: (1) To evaluate best overall response during treatment period confirmed in a 6-week follow-up, (2) PFS rate at 6 and 9 months, (3) Overall survival (OS) rate at 6, 12 months, and (4) Incidence of treatment-related adverse events (TRAEs). Methods: Inclusion criteria: Previously treated male and female subjects, > 18 years of age, pathologically confirmed diagnosis of locally advanced, unresectable, or metastatic sarcoma, measurable disease by RECIST v1.1, and acceptable hematologic and organ functions. Exclusion Criteria: History of autoimmune disorder. Treatment schedule: Metronomic doses of gemcitabine (600 mg/m2 max:1000 mg), doxorubicin (18 mg/m2; max: 32 mg), docetaxel (25 mg/m2; max:42 mg) on Day 1 and Day 8, and nivolumab (240 mg) on Day 1 only. Repeat treatment cycles may be given every three weeks if the toxicity grade is <1. Results: Efficacy (n = 70). This population completed at least one treatment cycle and had a follow-up CT or MRI scan at week 6. Best Overall Response = 14 PR, 47 SD, 9 PD. ORR = 20%; DCR (CR+PR+SD) was 87%. Median PFS was 8.2 (95% CI: 5.85-10.55) months; 6- month PFS rate of 59%. Median OS was 17.6 (95% CI: 13.53-21.67) months, with 6-month OS of 84%. Safety (n = 75): Grade 3/4 TRAEs include thrombocytopenia (n = 26), white blood cell count decreased (n = 17), neutropenia (n = 16), fatigue (n = 15), anemia (n = 13), nausea (n = 9), anorexia (n = 5), diarrhea (n = 2), emesis (n = 1), febrile neutropenia (n = 1), sepsis (n = 1), rectal bleeding (n = 1), transaminitis (n = 1), dizziness (n = 1), shortness of breath (n = 1). There were no unexpected adverse events reported. Conclusions: Taken together, the data suggests that nivolumab plus metronomic doses of gemcitabine, doxorubicin and docetaxel (1) may have synergistic activity, and (2) by indirect comparison, may be as effective as standard first line therapy for advanced sarcoma with manageable toxicity. Clinical trial information: NCT04535713 .
Epidemiology of undifferentiated sarcomas: A rare entity.
Authors: Ali Hassan , Prabhakaran Sivaguha Yadunath , Saleem Hafiz Muhammad Ajmal , Thirumaran Rajesh , Desai Krishna
Published: June 2024

e23571

Background: Undifferentiated Sarcomas (USar), previously known as malignant fibrous histiocytomas, are a group of rare and diverse malignant tumors of mesenchymal origin with a prevalence of 0.08-1 per 100,000. These are aggressive tumors with often high-grade morphology. The diagnosis is made by exclusion of other sarcoma entities upon bone marrow biopsy (criteria listed below). Undifferentiated sarcomas are of four major types, i.e. Pleomorphic, Epithelioid, spindle and round cells. The exact etiology of these sarcomas remains obscure, although many signaling pathways with various genetic alterations may be implicated in their development. The goal of this epidemiologic study is to assist in better understanding of this lesser known aggressive malignancy. Methods: The data was collected from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2022 Sub (2000-2020). We extracted undifferentiated sarcoma cases diagnosed between 0-90 years of age, using the ICD Code 8805/3. The analysis was stratified age, gender, race, & primary site labeled. The analysis was further completed by comparing survival using the Log-rank test (GraphPad Prism). Results: A total of 1680 cases of USar were identified, which were diagnosed between 2000 and 2020. Median age of diagnosis was 59.5 years. 50.54% were males and 49.46% were females. Of these cases, ~64.05% were Caucasians, ~15.18% Hispanics, ~10.48% Asians or Pacific Islanders, ~9.35% Black, and < 1% were Alaskan natives/American Indian and Non-Hispanics of unknown race. Further survival curves were compared based on gender, race and organ system. The average months of survival (MoS) based on gender showed no statistical significance (p value 0.6077). MoS calculated for Whites (28), Blacks (16), Asian & Pacific islanders (1), Alaskan natives & American-Indians (15), & Hispanics (21) (p value < 0.0001). MoS based on involved organ system were compared for: head/face/neck (18), GI tract (10), respiratory tract (4), heart/mediastinum/pleura (9), skin & soft tissue (51), bone (32), breast (30), GU (19), CNS (26), gynecological tract (12) and male reproductive system (29) (p < 0.0001). Conclusions: Undifferentiated Sarcoma accounts for less than 1% of all adult tumors. Only 1680 cases were found in the past twenty years, rendering it one of the rarest seen malignancies. Of the reported data, USar was most commonly observed in Caucasians. Comparing the survival curves also showed that there was no difference in survival based on gender. The highest MoS was seen in undifferentiated sarcomas of skin and soft tissues while respiratory tract tumors had the lowest average survival time. More research and analysis is warranted to understand this lesser known malignancy given its extremely low incidence.
Phase II Efficacy and Safety of 80 mg Osimertinib in Patients With Leptomeningeal Metastases Associated With Epidermal Growth Factor Receptor Mutation–Positive Non–Small Cell Lung Cancer (BLOSSOM)
Authors: Park Sehhoon , Baldry Richard , Jung Hyun Ae , Sun Jong-Mu , Lee Se-Hoon , Ahn Jin Seok , Kim Yu Jung , Lee Youngjoo , Kim Dong-Wan , Kim Sang-We , Lee Ki Hyeong , Lee Won Jae , Choi Jung Won , Chong Kyuha , Lee Jung-Il , Gwon So-Hyeon , Son Nak-Hoon , Ahn Myung-Ju
Published: June 2024

PURPOSE

Leptomeningeal metastases (LMs) exhibit a high incidence in patients with epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer (NSCLC) post-treatment with first- or second-generation EGFR tyrosine kinase inhibitors (TKIs). This investigation evaluates the efficacy, safety, and pharmacokinetics of 80 mg once daily osimertinib in patients with LMs resistant to prior first- or second-generation EGFR TKIs.

MATERIALS AND METHODS

In this phase II multicenter, open-label, single-arm study, 80 mg osimertinib was administered to patients with EGFR-mutated NSCLC who had developed LMs subsequent to treatment with prior EGFR TKIs. The primary end point was overall survival (OS), assessed alongside objective response rate by the blinded independent central review (BICR) and a pharmacokinetic analysis of plasma and cerebrospinal fluid (CSF) on the first day of cycles 3 and 6.

RESULTS

A total of 73 patients diagnosed with LM were treated with osimertinib, including 64 patients evaluable for the LM efficacy set—T790M negative (n = 62) and T790M positive (n = 2). The median OS in the full-analysis set was 15.6 months (95% CI, 11.5 to 20.2). The objective response rate for LM was 51.6%, including a 15.6% complete response, and the disease control rate was 81.3% by BICR in the LM efficacy evaluable set. The median LM progression-free survival by BICR was 11.2 months (95% CI, 7.7 to 15.3), the duration of response was 12.6 months (95% CI, 7.6 to 17.7), and OS was 15.0 months (95% CI, 11.3 to 18.7). Pharmacokinetic analysis showed that the CSF to free plasma osimertinib ratio was 22%. Most safety profiles were grade 1 and 2.

CONCLUSION

The study demonstrates significant intracranial efficacy and survival benefits of 80 mg once daily osimertinib in NSCLC patients with LMs. The data support considering daily 80 mg of osimertinib as a treatment option for EGFR-mutated NSCLC patients with LMs, irrespective of T790M mutation status.
TBX3 is essential for establishment of the posterior boundary of anterior genes and upregulation of posterior genes together with HAND2 during the onset of limb bud development
Authors: Soussi Geoffrey , Girdziusaite Ausra , Jhanwar Shalu , Palacio Victorio , Notaro Marco , Sheth Rushikesh , Zeller Rolf , Zuniga Aimée
Published: June 2024

During limb bud formation, axis polarities are established as evidenced by the spatially restricted expression of key regulator genes. In particular, the mutually antagonistic interaction between the GLI3 repressor and HAND2 results in distinct and non-overlapping anterior-distal Gli3 and posterior Hand2 expression domains. This is a hallmark of the establishment of antero-posterior limb axis polarity, together with spatially restricted expression of homeodomain and other transcriptional regulators. Here, we show that TBX3 is required for establishment of the posterior expression boundary of anterior genes in mouse limb buds. ChIP-seq and differential gene expression analysis of wild-type and mutant limb buds identifies TBX3-specific and shared TBX3-HAND2 target genes. High sensitivity fluorescent whole-mount in situ hybridisation shows that the posterior expression boundaries of anterior genes are positioned by TBX3-mediated repression, which excludes anterior genes such as Gli3, Alx4, Hand1 and Irx3/5 from the posterior limb bud mesenchyme. This exclusion delineates the posterior mesenchymal territory competent to establish the Shh-expressing limb bud organiser. In turn, HAND2 is required for Shh activation and cooperates with TBX3 to upregulate shared posterior identity target genes in early limb buds.
The Greek and the Cypriot financial crises
Authors: Ανθρακίδης Θεμιστοκλής
Published: June 2024

Ο σκοπός αυτής της διατριβής είναι να αναλύσει και να συγκρίνει τις πρόσφατες χρηματοπιστωτικές κρίσεις στην Ελλάδα και την Κύπρο από μια προσέγγιση συγκριτικής πολιτικής οικονομίας και να ανιχνεύσει το πολιτικό και οικονομικό περιβάλλον που προηγήθηκε και ακολούθησε αυτά τα επεισόδια κρίσης. Η μελέτη εμβαθύνει στις οικονομικές θεωρίες, τα πολιτικά συστήματα, τις ιδεολογικές δομές και τα θεσμικά πλαίσια που διαμόρφωσαν τις κρίσεις. Η συγκριτική πολιτική οικονομία παρέχει μια ολιστική προσέγγιση στην ανάλυση των οικονομικών και κοινωνικών δυναμικών, εξετάζοντας πολιτικές, κοινωνικές, νομικές και θεσμικές συνιστώσες και προσφέροντας μια ευρύτερη προοπτική από την συμβατική οικονομική ανάλυση. Αυτή η διατριβή αποσκοπεί να αποκαλύψει τα υποκείμενα αίτια και τις συνέπειες των κρίσεων στην Ελλάδα και την Κύπρο, καθώς και τις αντίστοιχες πολιτικές απαντήσεις σε αυτές. Αυτό θα επιτευχθεί με την εφαρμογή των νεοκλασικών και μετακεϋνσιανών οικονομικών θεωριών στις συνιστώσες της πολιτικής οικονομίας, τις οποίες ορίζει η διατριβή. Οι κρίσεις αυτές αποκάλυψαν αδυναμίες στις δημοσιονομικές πρακτικές, την ανταγωνιστικότητα, τις πολιτικές ανεπάρκειες και τους τραπεζικούς τομείς, παρουσιάζοντας ευρύτερες συστημικές προκλήσεις. Η διασύνδεση μεταξύ των ελληνικών και κυπριακών οικονομιών, ιδίως στα τραπεζικά τους συστήματα, προκάλεσε την κρίση στην Κύπρο μετά την αναδιάρθρωση του ελληνικού χρέους. Και οι δύο χώρες υιοθέτησαν μέτρα λιτότητας και λύσεις προσανατολισμένες στην απελευθέρωση της αγοράς που επιβλήθηκαν από την Τρόικα, αντικατοπτρίζοντας νεοκλασικές αρχές ευθυγραμμισμένες με την ατζέντα της Washington Consensus. Ωστόσο, εμφανίστηκαν διακριτές πορείες στην εφαρμογή πολιτικών, οι οποίες θα εξεταστούν διεξοδικά σε αυτή τη μελέτη. Συνολικά, αυτή η διατριβή υπογραμμίζει την ανάγκη για μια ολιστική, θεμελιωμένη προοπτική πολιτικής οικονομίας, στην εξήγηση και διαχείριση των χρηματοπιστωτικών κρίσεων, συνεισφέροντας σημαντικά στον διαλαμβανόμενο ακαδημαϊκό διάλογο. Η σχολαστική εξέταση των Προγραμμάτων Οικονομικής Προσαρμογής παρέχει πολύτιμες γνώσεις και ουσιαστικές συγκρίσεις μεταξύ Ελλάδας και Κύπρου και μεταξύ νεοκλασικών και μετακεϋνσιανών οικονομικών θεωριών, αποτελώντας μια ολοκληρωμένη ανάλυση για μελετητές και πολιτικούς που επιδιώκουν να κατανοήσουν τις μοναδικές προκλήσεις και πολιτικές απαντήσεις που προέκυψαν κατά τη διάρκεια των δύο κρίσεων.
Między tradycją a nowoczesnością: Jubileusz 60-lecia Stowarzyszenia Absolwentów Uniwersytetu Jagiellońskiego (1964–2024)
Authors: Stinia Maria
Published: June 2024

the Jagiellonian University Alumni Association, established in 1964, was founded and developed thanks to graduates who had the vision to maintain ties with their Alma Mater and continually contribute to it. Among the founders were represen-tatives of all fields of study. the Association was also open to graduates of the de-partments that were abolished or separated from the University by the communist authorities in the 1950s, and thanks to them, the idea of the pre-war Jagiellonian University was preserved. the main statutory tasks of maintaining ties with the Uni-versity, undertaking various forms of social activities for its benefit, popularizing its traditions and achievements as well as helping to organize scientific and self-educa-tion efforts of its members have been consistently carried out to this day. In the first period after the establishing, the organization focused on creating structures (including a dozen regional branches) and setting the tone of its activity. the initiatives taken were of a popular-scientific, cultural, educational, tourist, and sightseeing nature. the modes of activity followed good intelligentsia models of reg-ular contact with theater, poetry, prose, and music. the imposition of martial law in 1981 halted the work of the Association, sev-ered contacts and limited its functioning, which resulted in a significant decline in the number of members. As soon as it became possible, efforts were made to re-store normal operations. At present, the Association’s activity is based on extensive self-education of its members, active participation in the life of the University and undertaking urban space actions.
Troubled Pasts in Europe
Authors: Zupancic Rok , Kocan Faris , Andresen Kenneth , Bojarska Katarzyna , Dacosta Ricardo , Farrell Seamus , Fiedler Anke , Hoxha Abit , Ioannidis Nikandros , Kirk Niamh , Martín Cortes Irene , Milioni Dimitra L. , Panos Dionysis , Paradés Martín Marta , Rawski Tomasz , Triga Vasiliki , Vucko Tjasa
Published: June 2024

The overall aim of this monograph is to present the findings of a recently completed H2020 project, RePAST (1 April 2018–November 2021), which investigated how European societies deal with their troubled pasts today. In particular, the monograph aims at exploring what kind of actions could be taken and which strategies endorsed – both at the levels of policy making and civil society in the selected European states and the EU level – in order to facilitate the process of overcoming difficult historic legacies in several European states. The monograph is based on multidisciplinary and cross-country comparative research of how collective memory of contested pasts informs current conflicts and, based on that, what could be done by different states to de-intensify the present burden of historic conflicts in four different areas – history, media, politics, and arts and culture. Seven countries, where the troubled past resurfaces, are investigated; five EU member states, which joined the EU in different periods (Cyprus, Ireland, Spain, Germany and Poland), and two states in the EU neighbourhood (Kosovo, Bosnia and Herzegovina), where the EU is directly involved in the post-conflict stabilization efforts (including those related to overcoming troubled pasts).
Measurement of the linewidth of a home-built vacuum ultraviolet comb by frequency comb spectroscopy on NO2
Authors: Zhu MuFeng , Xiao ZhengRong , Zhang HengZhi , Hua LinQiang , Liu YangNi , Zuo Zhong , Xu SongPo , Liu XiaoJun
Published: June 2024

Optical frequency comb in the vacuum ultraviolet (VUV)/extreme ultraviolet (XUV) region has attracted a great deal of attention, as it provides coherent VUV/XUV radiation source with a rather narrow bandwidth, facilitating precise spectroscopic measurements in the short wavelength regime. In this study, we report on the linewidth measurement of a home-built VUV comb centered at 148 nm using direct frequency comb spectroscopy with NO2. The measurement reveals that the upper bound of our comb linewidth is less than 28 MHz. Fitting the whole trace with different repetition rates shows that the center frequency of the excitation is 2 021.25 ± 0.24 THz (∼148.32 nm). Thus, we assigned this excitation to the transition from the 6a1 orbital (ν1′=0, ν2′=0) to the 3pσ
u
orbital (ν1′=3, ν2′=8) in NO2. Our work demonstrates that VUV combs are potentially powerful tools for precision spectroscopic measurements in the short wavelength regime.
Tailoring the spectro-temporal mode of photon pairs generated from interspatial-mode four-wave mixing
Authors: Zhu Shengjie , Cui Liang , Li Xiaoying
Published: June 2024

We investigate the spectro-temporal mode property of the photon pairs generated via interspatial-mode spontaneous four-wave mixing (FWM) in a few-mode fiber (FMF) that supports two linearly polarized spatial modes in the 1550 nm telecom band. The two pulsed pumps for the process are in distinct spatial modes, while the created signal and idler photon pairs are also occupying different spatial modes. By exploiting the unique inter-mode phase matching condition in the FMF, we can tailor the spectro-temporal mode structure of the photon pairs by changing the pulse duration (spectral bandwidth) of the two pumps. Especially, photon pairs with a nearly round-shaped factorable joint spectrum are experimentally realized. The techniques are valuable for generating and manipulating quantum states in multi-mode waveguides and exploiting the spatial degree of freedom in quantum information processing.
Low phase noise self-injection-locked diode laser with a high-Q fiber resonator: model and experiment: publisher’s note
Authors: Ousaid Safia Mohand , Bourcier Germain , Fernandez Arnaud , Llopis Olivier , Lumeau Julien , Moreau Antonin , Bunel Thomas , Conforti Matteo , Mussot Arnaud , Crozatier Vincent , Balac Stéphane
Published: June 2024

This publisher’s note contains a correction to Opt. Lett. 49, 1933 (2024)10.1364/OL.514778.
Chromosome-level genome assemblies of 2 hemichordates provide new insights into deuterostome origin and chromosome evolution
Authors: Lin Che-Yi , Marlétaz Ferdinand , Pérez-Posada Alberto , Martínez-García Pedro Manuel , Schloissnig Siegfried , Peluso Paul , Conception Greg T. , Bump Paul , Chen Yi-Chih , Chou Cindy , Lin Ching-Yi , Fan Tzu-Pei , Tsai Chang-Tai , Gómez Skarmeta José Luis , Tena Juan J. , Lowe Christopher J. , Rank David R. , Rokhsar Daniel S. , Yu Jr-Kai , Su Yi-Hsien
Published: June 2024

Deuterostomes are a monophyletic group of animals that includes Hemichordata, Echinodermata (together called Ambulacraria), and Chordata. The diversity of deuterostome body plans has made it challenging to reconstruct their ancestral condition and to decipher the genetic changes that drove the diversification of deuterostome lineages. Here, we generate chromosome-level genome assemblies of 2 hemichordate species, Ptychodera flava and Schizocardium californicum, and use comparative genomic approaches to infer the chromosomal architecture of the deuterostome common ancestor and delineate lineage-specific chromosomal modifications. We show that hemichordate chromosomes (1N = 23) exhibit remarkable chromosome-scale macrosynteny when compared to other deuterostomes and can be derived from 24 deuterostome ancestral linkage groups (ALGs). These deuterostome ALGs in turn match previously inferred bilaterian ALGs, consistent with a relatively short transition from the last common bilaterian ancestor to the origin of deuterostomes. Based on this deuterostome ALG complement, we deduced chromosomal rearrangement events that occurred in different lineages. For example, a fusion-with-mixing event produced an Ambulacraria-specific ALG that subsequently split into 2 chromosomes in extant hemichordates, while this homologous ALG further fused with another chromosome in sea urchins. Orthologous genes distributed in these rearranged chromosomes are enriched for functions in various developmental processes. We found that the deeply conserved Hox clusters are located in highly rearranged chromosomes and that maintenance of the clusters are likely due to lower densities of transposable elements within the clusters. We also provide evidence that the deuterostome-specific pharyngeal gene cluster was established via the combination of 3 pre-assembled microsyntenic blocks. We suggest that since chromosomal rearrangement events and formation of new gene clusters may change the regulatory controls of developmental genes, these events may have contributed to the evolution of diverse body plans among deuterostomes.
Synergistic information supports modality integration and flexible learning in neural networks solving multiple tasks
Authors: Proca Alexandra M. , Rosas Fernando E. , Luppi Andrea I. , Bor Daniel , Crosby Matthew , Mediano Pedro A. M.
Published: June 2024

Striking progress has been made in understanding cognition by analyzing how the brain is engaged in different modes of information processing. For instance, so-calledsynergisticinformation (information encoded by a set of neurons but not by any subset) plays a key role in areas of the human brain linked with complex cognition. However, two questions remain unanswered: (a) how and why a cognitive system can become highly synergistic; and (b) how informational states map onto artificial neural networks in various learning modes. Here we employ an information-decomposition framework to investigate neural networks performing cognitive tasks. Our results show that synergy increases as networks learn multiple diverse tasks, and that in tasks requiring integration of multiple sources, performance critically relies on synergistic neurons. Overall, our results suggest that synergy is used to combine information from multiple modalities—and more generally for flexible and efficient learning. These findings reveal new ways of investigating how and why learning systems employ specific information-processing strategies, and support the principle that the capacity for general-purpose learning critically relies on the system’s information dynamics.
Data-driven learning of structure augments quantitative prediction of biological responses
Authors: Ha Yuanchi , Ma Helena R. , Wu Feilun , Weiss Andrea , Duncker Katherine , Xu Helen Z. , Lu Jia , Golovsky Max , Reker Daniel , You Lingchong
Published: June 2024

Multi-factor screenings are commonly used in diverse applications in medicine and bioengineering, including optimizing combination drug treatments and microbiome engineering. Despite the advances in high-throughput technologies, large-scale experiments typically remain prohibitively expensive. Here we introduce a machine learning platform, structure-augmented regression (SAR), that exploits the intrinsic structure of each biological system to learn a high-accuracy model with minimal data requirement. Under different environmental perturbations, each biological system exhibits a unique, structured phenotypic response. This structure can be learned based on limited data and once learned, can constrain subsequent quantitative predictions. We demonstrate that SAR requires significantly fewer data comparing to other existing machine-learning methods to achieve a high prediction accuracy, first on simulated data, then on experimental data of various systems and input dimensions. We then show how a learned structure can guide effective design of new experiments. Our approach has implications for predictive control of biological systems and an integration of machine learning prediction and experimental design.
Automatic mapping of high-risk urban areas for Aedes aegypti infestation based on building facade image analysis
Authors: Laranjeira Camila , Pereira Matheus , Oliveira Raul , Barbosa Gerson , Fernandes Camila , Bermudi Patricia , Resende Ester , Fernandes Eduardo , Nogueira Keiller , Andrade Valmir , Quintanilha José Alberto , dos Santos Jefersson A. , Chiaravalloti-Neto Francisco
Published: June 2024

Background

Dengue, Zika, and chikungunya, whose viruses are transmitted mainly by Aedes aegypti, significantly impact human health worldwide. Despite the recent development of promising vaccines against the dengue virus, controlling these arbovirus diseases still depends on mosquito surveillance and control. Nonetheless, several studies have shown that these measures are not sufficiently effective or ineffective. Identifying higher-risk areas in a municipality and directing control efforts towards them could improve it. One tool for this is the premise condition index (PCI); however, its measure requires visiting all buildings. We propose a novel approach capable of predicting the PCI based on facade street-level images, which we call PCINet.

Methodology

Our study was conducted in Campinas, a one million-inhabitant city in São Paulo, Brazil. We surveyed 200 blocks, visited their buildings, and measured the three traditional PCI components (building and backyard conditions and shading), the facade conditions (taking pictures of them), and other characteristics. We trained a deep neural network with the pictures taken, creating a computational model that can predict buildings’ conditions based on the view of their facades. We evaluated PCINet in a scenario emulating a real large-scale situation, where the model could be deployed to automatically monitor four regions of Campinas to identify risk areas.

Principal findings

PCINet produced reasonable results in differentiating the facade condition into three levels, and it is a scalable strategy to triage large areas. The entire process can be automated through data collection from facade data sources and inferences through PCINet. The facade conditions correlated highly with the building and backyard conditions and reasonably well with shading and backyard conditions. The use of street-level images and PCINet could help to optimize Ae. aegypti surveillance and control, reducing the number of in-person visits necessary to identify buildings, blocks, and neighborhoods at higher risk from mosquito and arbovirus diseases.
Entomological surveys and insecticide susceptibility profile of Aedes aegypti during the dengue outbreak in Sao Tome and Principe in 2022
Authors: Kamgang Basile , Acântara João , Tedjou Armel , Keumeni Christophe , Yougang Aurelie , Ancia Anne , Bigirimana Françoise , Clarke Sian E. , Gil Vilfrido Santana , Wondji Charles
Published: June 2024

Background

The first dengue outbreak in Sao Tome and Principe was reported in 2022. Entomological investigations were undertaken to establish the typology of Aedes larval habitats, the distribution of Ae. aegypti and Ae. albopictus, the related entomological risk and the susceptibility profile of Ae. aegypti to insecticides, to provide evidence to inform the outbreak response.

Methodology/Principal findings

Entomological surveys were performed in all seven health districts of Sao Tome and Principe during the dry and rainy seasons in 2022. WHO tube and synergist assays using piperonyl butoxide (PBO) and diethyl maleate (DEM) were carried out, together with genotyping of F1534C/V1016I/V410L mutations in Ae. aegypti. Aedes aegypti and Ae. albopictus were found in all seven health districts of the country with high abundance of Ae. aegypti in the most urbanised district, Agua Grande. Both Aedes species bred mainly in used tyres, discarded tanks and water storage containers. In both survey periods, the Breteau (BI > 50), house (HI > 35%) and container (CI > 20%) indices were higher than the thresholds established by WHO to indicate high potential risk of dengue transmission. The Ae. aegypti sampled were susceptible to all insecticides tested except dichlorodiphenyltrichloroethane (DDT) (9.2% mortality, resistant), bendiocarb (61.4% mortality, resistant) and alpha-cypermethrin (97% mortality, probable resistant). A full recovery was observed in Ae. aegypti resistant to bendiocarb after pre-exposure to synergist PBO. Only one Ae. aegypti specimen was found carrying F1534C mutation.

Conclusions/Significance

These findings revealed a high potential risk for dengue transmission throughout the year, with the bulk of larval breeding occurring in used tyres, water storage and discarded containers. Most of the insecticides tested remain effective to control Aedes vectors in Sao Tome, except DDT and bendiocarb. These data underline the importance of raising community awareness and implementing routine dengue vector control strategies to prevent further outbreaks in Sao Tome and Principe, and elsewhere in the subregion.
Modeling trajectories of physical aggression from infancy to pre-school age, their early predictors, and school-age outcomes
Authors: Nærde Ane , Janson Harald , Stoolmiller Mike
Published: June 2024

This study identified latent trajectories of physical aggression (TPA) from infancy to preschool age and evaluated (a) effects of early parent, parenting and child predictors on TPA as well as on social, behavioral, and academic functioning in Grade 2, and (b) TPA effects net of early predictor effects on Grade 2 functioning. We used data from the Behavior Outlook Norwegian Developmental Study (BONDS), which included 1,159 children (559 girls). Parents reported on risk and protective factors, and on physical aggression from 1 to 5 years of age; teachers reported on Grade 2 outcomes. We employed latent class growth curve analyses and identified nine TPA. In fully adjusted models simultaneously testing all associations among predictors, trajectories, and outcomes, maternal and paternal harsh parenting, child gender, and sibling presence predicted TPA, which significantly predicted externalizing and academic competence in Grade 2. Child gender had a pervasive influence on all outcomes as well as on TPA. To our knowledge, this is the first trajectory study to determine which predictors are most proximal, more distal, or just confounded, with their relative direct effect sizes, and to link early paternal as well as maternal harsh parenting practices with children’s TPA. Our findings underscore the need to include fathers in developmental research and early prevention and intervention efforts.
Mine water inrush source discrimination model based on KPCA-ISSA-KELM
Authors: Wang Wei , Cui Xinchao , Qi Yun , Xue Kailong , Liang Ran , Sun Zhipeng , Tao Hongjing
Published: June 2024

In order to ensure the safety of coal mine production, a mine water source identification model is proposed to improve the accuracy of mine water inrush source identification and effectively prevent water inrush accidents based on kernel principal component analysis (KPCA) and improved sparrow search algorithm (ISSA) optimized kernel extreme learning machine (KELM). Taking Zhaogezhuang mine as the research object, firstly, Na+, Ca2+, Mg2+, Cl-, SO2- 4 and HCO- 3 were selected as evaluation indexes, and their correlation was analyzed by SPSS27 software, with reducing the dimension of the original data by KPCA. Secondly, the Sine Chaotic Mapping, dynamic adaptive weights, and Cauchy Variation and Reverse Learning were introduced to improve the Sparrow Search Algorithm (SSA) to strengthen global search ability and stability. Meanwhile, the ISSA was used to optimize the kernel parameters and regularization coefficients in the KELM to establish a mine water inrush source discrimination model based on the KPCA-ISSA-KELM. Then, the mine water source data are input into the model for discrimination in compared with discrimination results of KPCA-SSA-KELM, KPCA-KELM, ISSA-KELM, SSA-KELM and KELM models. The results of the study show as follows: The discrimination results of the KPCA-ISSA-KELM model are in agreement with the actual results. Compared with the other models, the accuracy of the KPCA-ISSA-KELM model is improved by 8.33%, 12.5%, 4.17%, 21.83%, and 25%, respectively. Finally, when these models were applied to discriminate water sources in a coal mine in Shanxi, and the misjudgment rates of each model were 28.57%, 19.05%, 14.29%, 23.81%, 9.52% and 4.76%, respectively. From this, the KPCA-ISSA-KLEM model is the most accurate about discrimination and significantly better than other models in other evaluation indicators, verifying the universality and stability of the model. It can be effectively applied to the discrimination of inrush water sources in mines, providing important guarantees for mine safety production.
Rationale, conceptual issues, and resultant protocol for a mixed methods Person Trade Off (PTO) and qualitative study to estimate and understand the relative value of gains in health for children and young people compared to adults
Authors: Peasgood Tessa , Bailey Cate , Chen Gang , De Silva Ashwini , De Silva Perera Udeni , Norman Richard , Shah Koonal , Viney Rosalie , Devlin Nancy
Published: June 2024

Background

Economic evaluation of healthcare typically assumes that an identical health gain to different patients has the same social value. There is some evidence that the public may give greater value to gains for children and young people, although this evidence is not always consistent. We present a mixed methods study protocol where we aim to explore public preferences regarding health gains to children and young people relative to adults, in an Australian setting.

Methods

This study is a Person Trade Off (PTO) choice experiment that incorporates qualitative components. Within the PTO questions, respondents will be asked to choose between treating different groups of patients that may differ in terms of patient characteristics and group size. PTO questions will be included in an online survey to explore respondent views on the relative value of health gains to different age groups in terms of extending life and improving different aspects of quality of life. The survey will also contain attitudinal questions to help understand the impact of question style upon reported preferences. Additionally, the study will test the impact of forcing respondents to express a preference between two groups compared with allowing them to report that the two groups are equivalent. One-to-one ‘think aloud’, semi-structured interviews will be conducted to explore a sub-sample of respondents’ motivations and views in more detail. Focus groups will be conducted with members of the public to discuss the study findings and explore their views on the role of public preferences in health care prioritisation based on patient age.

Discussion

Our planned study will provide valuable information to healthcare decision makers in Australia who may need to decide whether to pay more for health gains for children and young people compared with adults. Additionally, the methodological test of forcing respondent choice or allowing them to express equivalence will contribute towards developing best practice methods in PTO studies. The rationale for and advantages of the study approach and potential limitations are discussed in the protocol.
Atomistic description of the OCTN1 recognition mechanism via in silico methods
Authors: Ben Mariem Omar , Palazzolo Luca , Torre Beatrice , Wei Yao , Bianchi Davide , Guerrini Uliano , Laurenzi Tommaso , Saporiti Simona , De Fabiani Emma , Pochini Lorena , Indiveri Cesare , Eberini Ivano
Published: June 2024

The Organic Cation Transporter Novel 1 (OCTN1), also known as SLC22A4, is widely expressed in various human tissues, and involved in numerous physiological and pathological processes remains. It facilitates the transport of organic cations, zwitterions, with selectivity for positively charged solutes. Ergothioneine, an antioxidant compound, and acetylcholine (Ach) are among its substrates. Given the lack of experimentally solved structures of this protein, this study aimed at generating a reliable 3D model of OCTN1 to shed light on its substrate-binding preferences and the role of sodium in substrate recognition and transport. A chimeric model was built by grafting the large extracellular loop 1 (EL1) from an AlphaFold-generated model onto a homology model. Molecular dynamics simulations revealed domain-specific mobility, with EL1 exhibiting the highest impact on overall stability. Molecular docking simulations identified cytarabine and verapamil as highest affinity ligands, consistent with their known inhibitory effects on OCTN1. Furthermore, MM/GBSA analysis allowed the categorization of substrates into weak, good, and strong binders, with molecular weight strongly correlating with binding affinity to the recognition site. Key recognition residues, including Tyr211, Glu381, and Arg469, were identified through interaction analysis. Ach demonstrated a low interaction energy, supporting the hypothesis of its one-directional transport towards to outside of the membrane. Regarding the role of sodium, our model suggested the involvement of Glu381 in sodium binding. Molecular dynamics simulations of systems at increasing levels of Na+ concentrations revealed increased sodium occupancy around Glu381, supporting experimental data associating Na+ concentration to molecule transport. In conclusion, this study provides valuable insights into the 3D structure of OCTN1, its substrate-binding preferences, and the role of sodium in the recognition. These findings contribute to the understanding of OCTN1 involvement in various physiological and pathological processes and may have implications for drug development and disease management.
Joint-specific regulation of homeobox D10 expression in rheumatoid arthritis fibroblast-like synoviocytes
Authors: Lee Hyeonjeong , Machado Camilla R. L. , Hammaker Deepa , Choi Eunice , Prideaux Edward B. , Wang Wei , Boyle David L. , Firestein Gary S.
Published: June 2024

Rheumatoid arthritis (RA) is a systemic immune-mediated disease characterized by joint inflammation and destruction. The disease typically affects small joints in the hands and feet, later progressing to involve larger joints such as the knees, shoulders, and hips. While the reasons for these joint-specific differences are unclear, distinct epigenetic patterns associated with joint location have been reported. In this study, we evaluated the unique epigenetic landscapes of fibroblast-like synoviocytes (FLS) from hip and knee synovium in RA patients, focusing on the expression and regulation of Homeobox (HOX) transcription factors. These highly conserved genes play a critical role in embryonic development and are known to maintain distinct expression patterns in various adult tissues. We found that several HOX genes, especially HOXD10, were differentially expressed in knee FLS compared with hip FLS. Epigenetic differences in chromatin accessibility and histone marks were observed in HOXD10 promoter between knee and hip FLS. Histone modification, particularly histone acetylation, was identified as an important regulator of HOXD10 expression. To understand the mechanism of differential HOXD10 expression, we inhibited histone deacetylases (HDACs) with small molecules and siRNA. We found that HDAC1 blockade or deficiency normalized the joint-specific HOXD10 expression patterns. These observations suggest that epigenetic differences, specifically histone acetylation related to increased HDAC1 expression, play a crucial role in joint-specific HOXD10 expression. Understanding these mechanisms could provide insights into the regional aspects of RA and potentially lead to therapeutic strategies targeting specific patterns of joint involvement during the course of disease.