bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risks, innovation, and adaptability in the UK’s incrementalism versus the European Union’s comprehensive artificial intelligence regulation
Authors: Gikay Asress Adimi 
Published: June 2024

Abstract
The regulation of artificial intelligence (AI) should strike a balance between addressing the risks of the technology and its benefits through enabling useful innovation whilst remaining adaptable to evolving risks. The European Union’s (EU) overarching risk-based regulation subjects AI systems across industries to a set of regulatory standards depending on where they fall in the risk bucket, whilst the UK’s sectoral approach advocates for an incremental regulation. By demonstrating the EU AI Act’s inability to adapt to evolving risks and regulate the technology proportionately, this article argues that the UK should avoid the EU AI Act’s compartmentalized high-risk classification system. The UK should refine its incremental regulation by adopting a generic principle for risk classification that allows for contextual risk assessment whilst adapting to evolving risks. The article contends that if refined appropriately, the UK’s incremental approach that relies on coordinate sectionalism encourages innovation without undermining the UK technology sector’s competitiveness in the global market of compliant AI, while also mitigating the potential risks presented by the technology.
New approaches to the control of chronic inflammatory diseases with a focus on the endolysosomal system of immune cells
Authors: Toyama-Sorimachi Noriko 
Published: June 2024

Abstract
Chronic inflammation is implicated in many types of diseases, including cardiovascular, neurodegenerative, metabolic, and immune disorders. The search for therapeutic targets to control chronic inflammation often involves narrowing down the various molecules associated with pathology that have been discovered by various omics analyses. Herein, a different approach to identify therapeutic targets against chronic inflammation is proposed and one such target is discussed as an example. In chronically inflamed tissues, a large number of cells receive diverse proinflammatory signals, the intracellular signals are intricately integrated, and complicated intercellular interactions are orchestrated. This review focuses on effectively blocking this chaotic inflammatory signaling network via the endolysosomal system, which acts as a cellular signaling hub. In endolysosomes, the inflammatory signals mediated by pathogen sensors, such as Toll-like receptors, and the signals from nutrient and metabolic pathways are integrally regulated. Disruption of endolysosome signaling results in a strong anti-inflammatory effect by disrupting various signaling pathways, including pathogen sensor-mediated signals, in multiple immune cells. The endolysosome-resident amino acid transporter, solute carrier family 15 member 4 (SLC15A4), which plays an important role in the regulation of endolysosome-mediated signals, is a promising therapeutic target for several inflammatory diseases, including autoimmune diseases. The mechanisms by which SLC15A4 regulates inflammatory responses may provide a proof of concept for the efficacy of therapeutic strategies targeting immune cell endolysosomes.
Effectiveness of Autologous Skin Cell Suspension in Large Total Body Surface Area Burns: Analysis of Clinical Outcomes and Patient Charges
Authors: Elkady Djoni , Larson Brandon M , Sharma Steffi , McNinch Neil L , Beaucock Beverly , Richard B Lou , Khandelwal Anjay 
Published: June 2024

Abstract
Autologous skin cell suspension (ASCS) is an adjunct to conventional split-thickness skin grafts (STSG) for acute burns, enhancing healing and reducing donor site requirements. This study validates ASCS’s predictive benefits in hospital stay reduction and cost savings by analyzing outcomes and real-world charges post-ASCS implementation at a single institution. A retrospective study (2018-2022) included burn patients with ≥10% TBSA. The study population comprised 2 groups: burns treated either with a combination of ASCS ± STSG or with STSG alone. Outcomes included LOS, surgeries, infection, complications, days on antibiotics, and adjusted charge per TBSA. The ASCS ± STSG group demonstrated significantly shorter LOS (Mdn: 16.0 days, IQR: 10-26) than the STSG group (Mdn: 20.0 days, IQR: 14-36; P = .017), and fewer surgeries (Mdn: 1.0, IQR: 1-2) versus the STSG group (Mdn: 1.0, IQR: 1-4; P = .020). Postoperative complications were significantly lower in ASCS ± STSG (11% vs. 36%; P &lt; .001). The STSG group had a longer distribution of antibiotic days (IQR: 0-7.0, min–max: 0-76) than the ASCS ± STSG group (IQR: 0-0, min–max: 0-37; P = .014). Wound infection incidence did not differ (P = .843). ASCS ± STSG showed a lower distribution of adjusted charge per TBSA (IQR: $10 788.5-$28 332.6) compared to the STSG group (IQR: $12 336.8-$29 507.3; P = .602) with a lower mean adjusted charge per TBSA ($20 995.0 vs. $24 882.3), although this was not statistically significant. ASCS ± STSG utilization demonstrated significant reductions in LOS, surgeries, postoperative complications, antibiotics, and potential cost savings. These findings underscore the practicality of integrating ASCS in burn management, offering substantial benefits to patients and healthcare institutions.
Biosensors for the detection of chorismate and cis,cis-muconic acid in Corynebacterium glutamicum
Authors: Velasquez-Guzman Jeanette C , Huttanus Herbert M , Morales Demosthenes P , Werner Tara S , Carroll Austin L , Guss Adam M , Yeager Chris M , Dale Taraka , Jha Ramesh K 
Published: June 2024

Abstract

Corynebacterium glutamicum ATCC 13032 is a promising microbial chassis for industrial production of valuable compounds, including aromatic amino acids derived from the shikimate pathway. In this work, we developed two whole-cell, transcription factor based fluorescent biosensors to track cis,cis-muconic acid (ccMA) and chorismate in C. glutamicum. Chorismate is a key intermediate in the shikimate pathway from which value-added chemicals can be produced, and a shunt from the shikimate pathway can divert carbon to ccMA, a high value chemical. We transferred a ccMA-inducible transcription factor, CatM, from Acinetobacter baylyi ADP1 into C. glutamicum and screened a promoter library to isolate variants with high sensitivity and dynamic range to ccMA by providing benzoate, which is converted to ccMA intracellularly. The biosensor also detected exogenously supplied ccMA, suggesting the presence of a putative ccMA transporter in C. glutamicum, though the external ccMA concentration threshold to elicit a response was 100-fold higher than the concentration of benzoate required to do so through intracellular ccMA production. We then developed a chorismate biosensor, in which a chorismate inducible promoter regulated by natively expressed QsuR was optimized to exhibit a dose-dependent response to exogenously supplemented quinate (a chorismate precursor). A chorismate–pyruvate lyase encoding gene, ubiC, was introduced into C. glutamicum to lower the intracellular chorismate pool, which resulted in loss of dose dependence to quinate. Further, a knockout strain that blocked the conversion of quinate to chorismate also resulted in absence of dose dependence to quinate, validating that the chorismate biosensor is specific to intracellular chorismate pool. The ccMA and chorismate biosensors were dually inserted into C. glutamicum to simultaneously detect intracellularly produced chorismate and ccMA. Biosensors, such as those developed in this study, can be applied in C. glutamicum for multiplex sensing to expedite pathway design and optimization through metabolic engineering in this promising chassis organism.

One-Sentence Summary
High-throughput screening of promoter libraries in Corynebacterium glutamicum to establish transcription factor based biosensors for key metabolic intermediates in shikimate and β-ketoadipate pathways.
Association between response to enfortumab vedotin and peripheral neuropathy in urothelial carcinoma patients: a multicenter retrospective study
Authors: Hayakawa Nozomi , Kikuchi Eiji , Kaneko Go , Yamashita Ryo , Ikarashi Daiki , Endo Yuki , Usui Kimitsugu , Obara Wataru , Oyama Masafumi , Kondo Yukihiro 
Published: June 2024

Abstract

Background
Enfortumab vedotin (EV) was approved for patients with metastatic urothelial carcinoma (mUC) who progressed after anticancer therapy on September 2021 in Japan. The association between the occurrence of EV-related side effects and clinical outcome remains to be elucidated.

Methods
We identified 97 mUC patients treated with EV therapy at our five institutions from the date of approval to March 2023. The median follow-up period was 7.0 months. We retrospectively analyzed the efficacy and safety of EV.

Results
The median age of the patients was 71 years old, 39% had PS of 1 or more, and 56.7% had primary tumor in upper urinary tract. Overall response rate (ORR) to EV therapy, median progression-free survival (PFS), and overall survival (OS) were 43.3%, 7.52 months, and 12.78 months, respectively. Any grade of treatment-related skin disorder, dysgeusia, peripheral neuropathy, gastrointestinal disorder, and hyperglycemia occurred in 61 (62.9%), 36 (37.1%), 34 (35.1%), 29 (29.9%), and 18 (18.6%) patients, respectively. The patients with EV-associated peripheral neuropathy had significantly higher ORR (58.8% vs. 34.9%, P = .032) and longer median PFS (8.05 vs. 6.31 months, P = .017) and OS (not reached vs. 11.57 months, P = .008, respectively) than those without. The occurrence of peripheral neuropathy after EV treatment and the presence of peritoneal dissemination were factors independently associated with PFS (hazard ratio = 0.46, P = .008 and hazard raito = 3.83, P = .004, respectively) and OS (hazard ratio = 0.30, P = .005 and hazard raito = 4.53, P = .002, respectively).

Conclusions
The occurrence of EV-related peripheral neuropathy might be associated with the efficacy of EV therapy in mUC patients.
Association of the modified Glasgow prognostic score and prognostic nutritional index with duration of oral anamorelin administration in patients with cancer cachexia: a retrospective cohort study
Authors: Fujita Kazuma , Akamine Yumiko , Igarashi Haruka , Fukushi Yayoi , Sasaki Katsuya , Fukuda Koji , Kikuchi Masafumi , Shibata Hiroyuki 
Published: June 2024

Abstract

Background
The modified Glasgow Prognostic Score (mGPS) and Prognostic Nutritional Index (PNI) are indicators of nutritional status in cancer patients; however, the effects of baseline mGPS and PNI on the duration of administration of the ghrelin receptor agonist anamorelin, which is used to treat cachexia in patients with cancer, are unclear. This study aimed to clarify the association of mGPS and PNI with the duration of oral anamorelin administration for patients who did not have beneficial effects from anamorelin.

Methods
The attending physician determined the duration of oral anamorelin administration based on discontinuation due to cancer progression, poor efficacy, adverse events, or death.

Results
The 12-week continuation rate of oral anamorelin was 30.4%. Univariate analysis revealed that an Eastern Cooperative Oncology Group performance status (ECOG-PS) of ≥2 (P &lt; .001), concurrent chemotherapy (P = .002), albumin level (P = .005), C-reactive protein level (P = .013), and a mGPS of 2 (P = .014) were statistically significant predictors of the 12-week continuation rate of oral anamorelin. In the multivariate analysis, a mGPS of 2 remained a significant risk factor, and the ECOG-PS and concurrent chemotherapy had no effect on the association between the mGPS and 12-week continuation rate of oral anamorelin.

Conclusion
Patients with a mGPS of 2, compared with mGPS of 0 or 1, are less likely to maintain oral anamorelin therapy, regardless of the ECOG-PS or concurrent chemotherapy. Therefore, it is necessary to consider initiating anamorelin administration at mGPS 0 or 1.
Breast cancer with biomarker reversal during the course of treatment: a case report
Authors: Yoshino Ryusei , Nakatsubo Masaki , Ujiie Nanami , Kitada Masahiro 
Published: June 2024

Abstract
During breast cancer recurrence, drug therapy is planned based on the biological characteristics of the primary tumor. However, the mechanisms underlying these changes have not yet been clarified. A 59-year-old woman underwent breast cancer surgery 23 years previously and received postoperative hormone therapy for 2 years. She had abdominal distention and ascites effusion and was diagnosed with carcinomatous peritonitis due to luminal-type breast cancer after ascites puncture. She received up to the fourth line of treatment. Subsequently, pleural effusion was observed and human epidermal growth factor receptor 2 type breast cancer was diagnosed because of pleurodesis. This case suggests that the cell block diagnostic method based on thoracic and ascites fluid cytology is useful not only for confirming the primary tumor but also for diagnosing the biological characteristics of breast cancer. In the treatment of breast cancer recurrence, it is important to plan the treatment, including aggressive re-biopsy of metastases.
Neutron star accretion events in AGN discs: mutimessenger implications
Authors: Zhang Shu-Rui , Yuan Ye-Fei , Wang Jian-Min , Ho Luis C 
Published: June 2024

ABSTRACT
This paper investigates the accretion of neutron stars (NSs) in active galactic nucleus (AGN) accretion discs. We classify potential accretion modes of NSs in AGN discs, proposing a hierarchical model of NS accretion: accretion flow from the Bondi sphere to accretion columns. The accretion of NSs in AGN discs differs from that of BHs, especially within the scale of the NS’s magnetosphere due to its hard surface and magnetic field. As the accretion flow approaches the magnetosphere, the magnetic fields guide the accretion flow to form accretion columns, primarily dominated by neutrinos. While neutrinos generated from single NS accretion may not have observable effects, considering the all-sky background, they contribute to the neutrino background in the sub-MeV energy range comparable to that of supernova explosions. NS accretion may also lead to the generation of mass quadrupole moments, consequently generating gravitational waves (GWs). The GWs, which exhibit characteristic effects like periodic modulations and echoes, could be observed by third-generation GW detectors. The emission of neutrinos and GWs carries away energy and angular momentum brought by accretion, reducing the feedback effect on the AGN disc. This results in an exceptionally high NS accretion rate, leading to a collapse time-scale shorter than the migration-merge time-scale, making it less likely that binary NS mergers originate from AGN discs.
Damping wing-like features in the stacked Ly α forest: Potential neutral hydrogen islands at z &lt; 6
Authors: Zhu Yongda , Becker George D , Bosman Sarah E I , Cain Christopher , Keating Laura C , Nasir Fahad , D’Odorico Valentina , Bañados Eduardo , Bian Fuyan , Bischetti Manuela , Bolton James S , Chen Huanqing , D’Aloisio Anson , Davies Frederick B , Davies Rebecca L , Eilers Anna-Christina , Fan Xiaohui , Gaikwad Prakash , Greig Bradley , Haehnelt Martin G , Kulkarni Girish , Lai Samuel , Puchwein Ewald , Qin Yuxiang , Ryan-Weber Emma V , Satyavolu Sindhu , Spina Benedetta , Walter Fabian , Wang Feige , Wolfson Molly , Yang Jinyi 
Published: June 2024

ABSTRACT
Recent quasar absorption line observations suggest that reionization may end as late as $z \approx 5.3$. As a means to search for large neutral hydrogen islands at $z\ \lt\ 6$, we revisit long dark gaps in the Ly $\beta$ forest in Very Large Telescope/X-Shooter and Keck/Echellette Spectrograph and Imager quasar spectra. We stack the Ly $\alpha$ forest corresponding to both edges of these Ly $\beta$ dark gaps and identify a damping wing-like extended absorption profile. The average redshift of the stacked forest is $z=5.8$. By comparing these observations with reionization simulations, we infer that such a damping wing-like feature can be naturally explained if these gaps are at least partially created by neutral islands. Conversely, simulated dark gaps lacking neutral hydrogen struggle to replicate the observed damping wing features. Furthermore, this damping wing-like profile implies that the volume-averaged neutral hydrogen fraction must be $\langle x_{\rm H\,{\small {I}}} \rangle \ge 6.1 \pm 3.9~{{\ \rm per\ cent}}$ at $z = 5.8$. Our results offer robust evidence that reionization extends below $z=6$.
Assessing the impact of transcriptomics data analysis pipelines on downstream functional enrichment results
Authors: Paton Victor , Ramirez Flores Ricardo Omar , Gabor Attila , Badia-i-Mompel Pau , Tanevski Jovan , Garrido-Rodriguez Martin , Saez-Rodriguez Julio 
Published: June 2024

Abstract
Transcriptomics is widely used to assess the state of biological systems. There are many tools for the different steps, such as normalization, differential expression, and enrichment. While numerous studies have examined the impact of method choices on differential expression results, little attention has been paid to their effects on further downstream functional analysis, which typically provides the basis for interpretation and follow-up experiments. To address this, we introduce FLOP, a comprehensive nextflow-based workflow combining methods to perform end-to-end analyses of transcriptomics data. We illustrate FLOP on datasets ranging from end-stage heart failure patients to cancer cell lines. We discovered effects not noticeable at the gene-level, and observed that not filtering the data had the highest impact on the correlation between pipelines in the gene set space. Moreover, we performed three benchmarks to evaluate the 12 pipelines included in FLOP, and confirmed that filtering is essential in scenarios of expected moderate-to-low biological signal. Overall, our results underscore the impact of carefully evaluating the consequences of the choice of preprocessing methods on downstream enrichment analyses. We envision FLOP as a valuable tool to measure the robustness of functional analyses, ultimately leading to more reliable and conclusive biological findings.
PRPF40A induces inclusion of exons in GC-rich regions important for human myeloid cell differentiation
Authors: Tan Cheryl Weiqi , Sim Donald Yuhui , Zhen Yashu , Tian Haobo , Koh Jace , Roca Xavier 
Published: June 2024

Abstract
We characterized the regulatory mechanisms and role in human myeloid cell survival and differentiation of PRPF40A, a splicing factor lacking a canonical RNA Binding Domain. Upon PRPF40A knockdown, HL-60 cells displayed increased cell death, decreased proliferation and slight differentiation phenotype with upregulation of immune activation genes. Suggestive of both redundant and specific functions, cell death but not proliferation was rescued by overexpression of its paralog PRPF40B. Transcriptomic analysis revealed the predominant role of PRPF40A as an activator of cassette exon inclusion of functionally relevant splicing events. Mechanistically, the exons exclusively upregulated by PRPF40A are flanked by short and GC-rich introns which tend to localize to nuclear speckles in the nucleus center. These PRPF40A regulatory features are shared with other splicing regulators such as SRRM2, SON, PCBP1/2, and to a lesser extent TRA2B and SRSF2, as a part of a functional network that regulates splicing partly via co-localization in the nucleus.
The IDH paradox: Meta-analysis of alkylating chemotherapy in IDH-wild type and -mutant lower grade gliomas
Authors: Kinslow Connor J , Roy Soumyajit , Iwamoto Fabio M , Brown Paul D , DeStephano David M , Canoll Peter D , Qureshi Summer S , Gallito Matthew , Sisti Michael B , Bruce Jeffrey N , Horowitz David P , Kachnic Lisa A , Neugut Alfred I , Yu James B , Mehta Minesh P , Cheng Simon K , Wang Tony J C 
Published: June 2024

Abstract

Background
IDH-wild type (-wt) status is a prerequisite for the diagnosis of glioblastoma (GBM); however, IDH-wt gliomas with low-grade or anaplastic morphology have historically been excluded from GBM trials and may represent a distinct prognostic entity. While alkylating agent chemotherapy improves overall survival (OS) and progression-free survival (PFS) for IDH-wt GBM and also IDH-mutant gliomas, irrespective of grade, the benefit for IDH-wt diffuse histologic lower-grade gliomas is unclear.

Methods
We performed a meta-analysis of randomized clinical trials for World Health Organization (WHO) grades 2–3 gliomas (2009 to present) to determine the effect of alkylating chemotherapy on IDH-wt and -mutant gliomas using a random-effects model with inverse-variance pooling.

Results
We identified 6 trials with 1204 patients (430 IDH-wt, 774 IDH-mutant) that evaluated alkylating chemoradiotherapy versus radiotherapy alone, allowing us to perform an analysis focused on the value of adding alkylating chemotherapy to radiotherapy. For patients with IDH-wt tumors, alkylating chemotherapy added to radiotherapy was associated with improved PFS (HR:0.77 [95% CI: 0.62–0.97], P = .03) but not OS (HR:0.87 [95% CI: 0.64–1.18], P = .17). For patients with IDH-mutant tumors, alkylating chemotherapy added to radiotherapy improved both OS (HR:0.52 [95% CI: 0.42–0.64], P &lt; .001) and PFS (HR = 0.47 [95% CI: 0.39–0.57], P &lt; .001) compared to radiotherapy alone. The magnitude of benefit was similar for IDH-mutant gliomas with or without 1p19q-codeletion.

Conclusions
Alkylating chemotherapy reduces mortality by 48% and progression by 53% for patients with IDH-mutant gliomas. Optimal management of IDH-wt diffuse histologic lower-grade gliomas remains to be determined, as there is little evidence supporting an OS benefit from alkylating chemotherapy.
Revisiting Representations of Quark Mixing Matrix
Authors: Kaur Gurjit , Bagai Aakriti , Ahuja Gulsheen , Gupta Manmohan 
Published: June 2024

Abstract
Using unitarity, unlike the approaches available in the literature, we construct 9 independent representations of the Cabibbo–Kobayashi–Maskawa) CKM matrix starting with each of the 9 elements of the matrix. The relationship of these independently constructed representations with those already available in the literature is compared and discussed. Further, the implications of these representations are explored for some of the CKM parameters such as $\delta$, J and $\epsilon _k$. Interestingly, we find that the PDG representation which is equivalent to our first representation seems to be most appropriate to incorporate the hierarchy of the elements of the CKM matrix as well as to describe the related phenomenology.