bluuebunny/crossref_metadata_2025 huggingface dataset:
Orientia tsutsugamushi:
comprehensive analysis of the mobilome of a highly fragmented and repetitive genome reveals the capacity for ongoing lateral gene transfer in an obligate intracellular bacterium
Authors: Giengkam Suparat , Kullapanich Chitrasak , Wongsantichon Jantana , Adcox Haley E. , Gillespie Joseph J. , Salje Jeanne
Published: October 2023

The rickettsial human pathogen
Orientia tsutsugamushi
(Ot) is an obligate intracellular Gram-negative bacterium with one of the most highly fragmented and repetitive genomes of any organism. Around 50% of its ~2.3-Mb genome is composed of repetitive DNA that is derived from the highly proliferated Rickettsiales amplified genetic element (RAGE). RAGE is an integrative and conjugative element (ICE) that is present in a single Ot genome in up to 93 copies, most of which are partially or heavily degraded. In this report, we analyzed RAGEs in eight fully sequenced Ot genomes and manually curated and re-annotated all RAGE-associated genes, including those encoding DNA mobilization proteins, P-type (
vir
), and F-type (
tra
) type IV secretion system (T4SS) components, ankyrin repeat- and tetratricopeptide repeat-containing effectors, and other piggybacking cargo. Originally, the heavily degraded Ot RAGEs have led to speculation that they are remnants of historical ICEs that are no longer active. Our analysis, however, identified two Ot genomes harboring one or more intact RAGEs with complete
F-T4SS
genes essential for mediating ICE DNA transfer. As similar ICEs have been identified in unrelated rickettsial species, we assert that RAGEs may play an ongoing role in lateral gene transfer within the Rickettsiales. We also identified a conserved set of gene transfer agent genes in all Ot genomes. Together these findings indicate that, despite their obligate intracellular lifestyle and host range restricted to mites, rodents, and humans, Ot genomes are highly dynamic and shaped through ongoing invasions by mobile genetic elements and virus-like elements.

IMPORTANCE

Obligate intracellular bacteria, or those only capable of growth inside other living cells, have limited opportunities for horizontal gene transfer with other microbes due to their isolated replicative niche. The human pathogen Ot, an obligate intracellular bacterium causing scrub typhus, encodes an unusually high copy number of a ~40 gene mobile genetic element that typically facilitates genetic transfer across microbes. This proliferated element is heavily degraded in Ot and previously assumed to be inactive. Here, we conducted a detailed analysis of this element in eight Ot strains and discovered two strains with at least one intact copy. This implies that the element is still capable of moving across Ot populations and suggests that the genome of this bacterium may be even more dynamic than previously appreciated. Our work raises questions about intracellular microbial evolution and sounds an alarm for gene-based efforts focused on diagnosing and combatting scrub typhus.
Interactions among human papillomavirus proteins and host DNA repair factors differ during the viral life cycle and virus-induced tumorigenesis
Authors: Wendel Sebastian , Wallace Nicholas A.
Published: October 2023

This review focuses on the impact of human papillomavirus (HPV) oncogenes on DNA repair pathways with a particular focus on how these relationships change as productive HPV infections transition to malignant lesions. We made specific efforts to incorporate advances in the understanding of HPV and DNA damage repair over the last 4 years. We apologize for any articles that we missed in compiling this report.
Survival in a young child with out-of-hospital cardiac arrest: diagnostic dilemma and when to deviate from standard resuscitation guidelines
Authors: Collins Neil John , Finn Daragh , O'Mahony Olivia , Walsh Mark
Published: October 2023

A boy in early childhood presented in cardiac arrest. Care was provided out of hospital and in the emergency department as per standard paediatric resuscitation guidelines. Despite initial return of spontaneous circulation following cardiopulmonary resuscitation, two defibrillation shocks and epinephrine via intraosseous access, he had recurrent episodes of pulseless ventricular tachycardia and ventricular fibrillation. In total, 40 defibrillation shocks were administered, and he subsequently stabilised on combined treatment with intravenous esmolol, amiodarone and milrinone. He was transferred to the paediatric intensive care unit and had an automated implantable cardioverter–defibrillator inserted prior to discharge. Genetic testing has confirmed a diagnosis of catecholaminergic polymorphic ventricular tachycardia and it is hypothesised that the childhood excitement at a popular time of year, combined with caffeinated drinks, instigated his initial cardiac arrest which was propagated with iatrogenic epinephrine. He has remained stable since, with no neurological sequelae thus far from a significantly prolonged downtime.
Racialised staff–patient relationships in inpatient mental health wards: a realist secondary qualitative analysis of patient experience data
Authors: Hua Phuong , Shakoor Sania , Fenton Sarah-Jane , Freestone Mark , Weich Scott , Bhui Kamaldeep
Published: October 2023

Background

The current study is a secondary analysis of qualitative data collected as part of EURIPIDES, a study which assessed how patient experience data were used to improve the quality of care in National Health Service (NHS) mental health services.

Objective

We undertook a detailed realist secondary qualitative analysis of 10 interviews in which expressions of racialisation were unexpectedly reported. This theme and these data did not form part of the primary realist evaluation.

Methods

Interviews were originally conducted with the patients (18–65 years: 40% female, 60% male) from four different geographically located NHS England mental health trusts between July and October 2017. Secondary qualitative data analysis was conducted in two phases: (1) reflexive thematic analysis and retroduction; (2) refinement of context–mechanism–outcome configurations to explore the generative mechanisms underpinning processes of racialisation and revision of the initial programme theory.

Findings

There were two main themes: (1) absence of safe spaces to discuss racialisation which silenced and isolated patients; (2) strained communication and power imbalances shaped a process of mutual racialisation by patients and staff. Non-reporting of racialisation and discrimination elicited emotions such as feeling othered, misunderstood, disempowered and fearful.

Conclusions

The culture of silence, non-reporting and power imbalances in inpatient wards perpetuated relational racialisation and prevented authentic feedback and staff–patient rapport.

Clinical implications

Racialisation in mental health trusts reflects lack of psychological safety which weakens staff–patient rapport and has implications for authentic patient engagement in feedback and quality improvement processes. Larger-scale studies are needed to investigate racialisation in the staff–patient relationships.
High versus low positive end-expiratory pressure setting in patients receiving veno-venous extracorporeal membrane oxygenation support for severe acute respiratory distress syndrome: study protocol for the multicentre, randomised ExPress SAVER Trial
Authors: Nishikimi Mitsuaki , Ohshimo Shinichiro , Hamaguchi Jun , Fujizuka Kenji , Hagiwara Yoshihiro , Anzai Tatsuhiko , Ishii Junki , Ogata Yoshitaka , Aokage Toshiyuki , Ikeda Tokuji , Yagi Tsukasa , Suzuki Ginga , Ishikura Ken , Katsuta Ken , Konno Daisuke , Hattori Noriyuki , Nakamura Tomoyuki , Matsumura Yosuke , Kasugai Daisuke , Kikuchi Hitoshi , Iino Tatsuhiko , Kai Shinichi , Hashimoto Haruka , Yoshida Takeshi , Igarashi Yumi , Ogura Takayuki , Matsumura Kazuki , Shimizu Keiki , Nakamura Mitsunobu , Ichiba Shingo , Takahashi Kunihiko , Shime Nobuaki
Published: October 2023

Introduction

While limiting the tidal volume to 6 mL/kg during veno-venous extracorporeal membrane oxygenation (V-V ECMO) to ameliorate lung injury in patients with acute respiratory distress syndrome (ARDS) is widely accepted, the best setting for positive end-expiratory pressure (PEEP) is still controversial. This study is being conducted to investigate whether a higher PEEP setting (15 cmH2O) during V-V ECMO can decrease the duration of ECMO support needed in patients with severe ARDS, as compared with a lower PEEP setting.

Methods and analysis

The study is an investigator-initiated, multicentre, open-label, two-arm, randomised controlled trial conducted with the participation of 20 intensive care units (ICUs) at academic as well as non-academic hospitals in Japan. The subjects of the study are patients with severe ARDS who require V-V ECMO support. Eligible patients will be randomised equally to the high PEEP group or low PEEP group. Recruitment to the study will continue until a total of 210 patients with ARDS requiring V-V ECMO support have been randomised. In the high PEEP group, PEEP will be set at 15 cmH2O from the start of V-V ECMO until the trials for liberation from V-V ECMO (or until day 28 after the allocation), while in the low PEEP group, the PEEP will be set at 5 cmH2O. Other treatments will be the same in the two groups. The primary endpoint of the study is the number of ECMO-free days until day 28, defined as the length of time (in days) from successful libration from V-V ECMO to day 28. The secondary endpoints are mortality on day 28, in-hospital mortality on day 60, ventilator-free days during the first 60 days and length of ICU stay.

Ethics and dissemination

Ethics approval for the trial at all the participating hospitals was obtained on 27 September 2022, by central ethics approval (IRB at Hiroshima University Hospital, C2022-0006). The results of this study will be presented at domestic and international medical congresses, and also published in scientific journals.

Trial registration number

The Japan Registry of Clinical Trials jRCT1062220062. Registered on 28 September 2022.

Protocol version

28 March 2023, version 4.0.
Construction and validation of safe care theory for older inpatients from the perspective of socio-ecological model: a study protocol
Authors: Yan Lupei , Liu Li , Wang Fang , Hu Xiuying
Published: October 2023

Introduction

In an ageing society, older adults are the main users of healthcare services, and Chinese healthcare systems have been struggling to meet the care demand of older adults. Due to the illness, many older inpatients cannot finish daily activities independently and require healthcare from caregivers. Evaluating the care needs of older adults and exploring the factors affecting safe care at multiple levels are conducive to providing systematic care services for older inpatients. This study aims to examine which and how factors impact safe care for older inpatients and propose a safe care theory to provide directions on improving the safe care system in the hospital.

Methods and analysis

A mixed-methods study with three interrelated research streams will be designed. (1) A safe care concept model: we will conduct a scoping review to extract the facilitators and barriers influencing the safe care of older inpatients and construct a concept model based on the socio-ecological model and the Yorkshire Contributory Factors Framework. (2) A safe care theory model: we will conduct a qualitative study with thematic analysis (aimed at older inpatients, caregivers and nurses) to define the concept connotations and propose a theory model. (3) A safe care theory: we will use the scales related to the theory model to test the concepts and statements. We will revise the theory model and derive a safe care theory based on the mixed-methods study results. This study will start in October 2023 and end in October 2025.

Ethics and dissemination

This study was approved by the ethics committee (No. 20221598). All participants will be provided with consent forms prior to data collection. The study will be disseminated via peer-reviewed manuscripts and conferences.

Trial registration number

ChiCTR2300067421.
Representation of ethnic and racial minority groups in European vaccine trials: a quantitative analysis of clinical trials registries
Authors: Puttick Natasha F , Vanderslott Samantha , Tanner Rachel
Published: October 2023

Objectives

The representation of ethnic minority groups in European vaccine trials is an important and hitherto unaddressed gap in the literature. The objectives of this study were to determine the proportion of European vaccine trials that report data on the ethnic demographics of participants, to evaluate the distribution of ethnic minority groups among trial participants (where reported), and ascertain whether this is representative of the wider population of the country.

Design

We evaluated the representation of ethnic/racial minority groups in clinical research, conducting a quantitative analysis of clinical trials registry data from completed vaccine trials in Europe that commenced between 1 January 2010 and 31 December 2020.

Data sources

Data were collected from four major clinical trial databases: ClinicalTrials.gov, the European Union Clinical Trials Register (EUCTR), the International Standard Randomised Controlled Trial Number (ISRCTN) and the International Clinical Trials Registry Platform (ICTRP).

Results

A majority of clinical trials failed to either record or report the race/ethnicity of their volunteers on the clinical trials registry databases. Reported participants in UK vaccine trials were not representative of the ethnic demographics of the wider population. Unavailability of population-level ethnicity data for many European countries was a significant barrier to determining the wider applicability of these findings.

Conclusions

Under-representation of ethnic minority groups in vaccine trials may have implications for the effectiveness of routine vaccinations, threatening the principles of justice and equity that are embedded in national medical research guidelines. Unavailability of population-level ethnicity data exacerbates the prevailing lack of understanding of the extent of this issue, despite literature indicating cause for concern.
Phase II trial of nivolumab and metformin in patients with treatment-refractory microsatellite stable metastatic colorectal cancer
Authors: Akce Mehmet , Farran Batoul , Switchenko Jeffrey M , Rupji Manali , Kang Sandra , Khalil Lana , Ruggieri-Joyce Amanda , Olson Brian , Shaib Walid L , Wu Christina , Alese Olatunji B , Diab Maria , Lesinski Gregory B , El-Rayes Bassel F
Published: October 2023

Background

Preclinical studies showed metformin reduces exhaustion of tumor-infiltrating lymphocytes and potentiates programmed cell death protein-1 (PD-1) blockade. We hypothesized that metformin with nivolumab would elicit potent antitumor and immune modulatory activity in metastatic microsatellite stable (MSS) colorectal cancer (CRC). We evaluated this hypothesis in a phase II study.

Methods

Nivolumab (480 mg) was administered intravenously every 4 weeks while metformin (1000 mg) was given orally, two times per day following a 14-day metformin only lead-in phase. Patients ≥18 years of age, with previously treated, stage IV MSS CRC, and Eastern Cooperative Oncology Group 0–1, having received no prior anti-PD-1 agent were eligible. The primary endpoint was overall response rate with secondary endpoints of overall survival (OS) and progression-free survival (PFS). Correlative studies using paired pretreatment/on-treatment biopsies and peripheral blood evaluated a series of immune biomarkers in the tumor microenvironment and systemic circulation using ChipCytometry and flow cytometry.

Results

A total of 24 patients were enrolled, 6 patients were replaced per protocol, 18 patients had evaluable disease. Of the 18 evaluable patients, 11/18 (61%) were women and the median age was 58 (IQR 50–67). Two patients had stable disease, but no patients had objective response, hence the study was stopped for futility. Median OS and PFS was 5.2 months (95% CI (3.2 to 11.7)) and 2.3 months (95% CI (1.7 to 2.3)). Most common grade 3/4 toxicities: Anemia (n=2), diarrhea (n=2), and fever (n=2). Metformin alone failed to increase the infiltration of T-cell subsets in the tumor, but combined metformin and nivolumab increased percentages of tumor-infiltrating leukocytes (p=0.031). Dual treatment also increased Tim3+ levels in patient tissues and decreased naïve CD8+T cells (p=0.0475).

Conclusions

Nivolumab and metformin were well tolerated in patients with MSS CRC but had no evidence of efficacy. Correlative studies did not reveal an appreciable degree of immune modulation from metformin alone, but showed trends in tumorous T-cell infiltration as a result of dual metformin and PD-1 blockade despite progression in a majority of patients.
Temporal progression of functional independence after mechanical thrombectomy in acute vertebrobasilar artery occlusions
Authors: Xu Yingjie , Zhang Pan , Li Wei , Wang Jinjing , Xiao Lulu , Huang Xianjun , Duan Zuowei , Li Yongkun , Peng Feng , Zhang Feng , Luo Genpei , Sun Wen
Published: October 2023

Background

Neurological recovery after endovascular treatment (EVT) for large vessel occlusion stroke often has diverse timelines. Understanding the temporal progression of functional independence after EVT, especially delayed functional independence (DFI) and highly delayed functional independence (HDFI), in patients who do not improve early is essential for prognostication and rehabilitation. We aimed to analyze the prevalence and predictors of DFI and HDFI after EVT in acute vertebrobasilar artery occlusions (VBAO).

Methods

Patients with VBAO who received EVT in China were retrospectively enrolled. Early functional independence (EFI) was defined as a modified Rankin Scale (mRS) score of 0–2 at discharge. The incidence and predictors of DFI (mRS score 0–2 at 90 days in non-EFI patients) and HDFI (mRS score 0–2 at 1 year in non-DFI patients) were analyzed.

Results

2422 patients met the study criteria. EFI was observed in 20% (483) of patients. Among non-EFI patients, DFI was observed in 21% (395/1880). HDFI was observed in 13% (191/1439) of non-DFI patients. Younger age (P=0.006), lower pre-EVT National Institutes of Health Stroke Scale (NIHSS) score (P<0.001), higher posterior circulation-Alberta Stroke Program Early CT Score (PC-ASPECTS) (P=0.012), and absence of symptomatic intracranial hemorrhage (sICH) (P<0.001) were predictors of DFI. Predictors of HDFI were younger age (P<0.001) and lower pre-EVT NIHSS score (P<0.001).

Conclusion

A considerable proportion of patients have DFI and HDFI. The independent predictors of DFI were younger age, lower pre-EVT NIHSS score, higher PC-ASPECTS, and absence of sICH. Predictors of HDFI included younger age and lower pre-EVT NIHSS score.
Pompe disease misdiagnosed as polymyositis
Authors: Camelo-Filho Antonio Edvan , Martins Manoel Ricardo Alves , Souza Jorge Luiz de Brito de , Maurício Rebeca Bessa , Nóbrega Paulo Ribeiro
Published: October 2023

Late-onset Pompe disease manifests predominantly in the proximal lower limbs and may be mistaken for an inflammatory myopathy. A 46-year-old man with acromegaly had an 8-year history of progressive weakness. His myopathy was initially attributed to the acromegaly, but severe progression prompted a muscle biopsy, which suggested an inflammatory myopathy. However, his weakness progressed despite treatment for polymyositis. His muscle ultrasound scan pattern was more suggestive of Pompe disease than polymyositis, and Pompe disease was confirmed by genetic and enzymatic testing. Patients with apparent polymyositis, which persists despite treatment, require reconsideration of the diagnosis, with particular attention to treatable genetic causes.
Fusion of sparse non-co-located measurements from multiple sources for geotechnical site investigation
Authors: Guan Zheng , Wang Yu , Phoon Kok-Kwang
Published: October 2023

A profile of geotechnical properties is often needed for geotechnical design and analysis. However, site-specific data might be characterized as MUSIC-X (i.e., Multivariate, Uncertain and Unique, Sparse, Incomplete, and potentially Corrupted with “X” denoting the spatial/temporal variability), posing a significant challenge in accurately interpreting geotechnical property profiles. Different sources, or types, of data are commonly available from a specific site investigation program, and they are usually cross-correlated, and thus can provide complementary information. This leads to an important question in geotechnical site investigation: how to integrate multiple sources of sparse data for enhancing the profiling of different geotechnical properties. To address this issue, this study proposes a novel method, called fusion Bayesian compressive sampling (Fusion-BCS), for integrating sparse and non-co-located geotechnical data. In the proposed method, the auto- and cross-correlation structures of different sources of data are exploited in a data-driven manner through a joint sparse representation. Then, profiles of different geotechnical properties are jointly reconstructed from all measurements under a framework of compressive sampling/sensing. The proposed method is illustrated using simulated and real geotechnical data. The results indicate that the accuracy of the interpreted geotechnical property profiles may be significantly improved by integrating multiple sources of site investigation data.
Massive scalar field perturbations in Weyl black holes
Authors: Bécar Ramón , González P. A. , Moncada Felipe , Vásquez Yerko
Published: October 2023

In this work we consider the propagation of massive scalar fields in the background of Weyl black holes, and we study the effect of the scalar field mass in the spectrum of the quasinormal frequencies (QNFs) via the Wentzel–Kramers–Brillouin (WKB) method and the pseudo-spectral Chebyshev method. The spectrum of QNFs is described by two families of modes: the photon sphere and the de Sitter modes. Essentially, we show via the WKB method that the photon sphere modes exhibit an anomalous behaviour of the decay rate of the QNFs; that is, the longest-lived modes are the ones with higher angular numbers, and there is a critical value of the scalar field mass beyond which the anomalous behaviour is inverted. We also analyse the effect of the scalar field mass on each family of modes and on their dominance, and we give an estimated value of the scalar field mass where the interchange in the dominant family occurs.
Novel Computational Approaches to the Universe
Authors: Schumann Andrew , Król Jerzy
Published: October 2023

In the paper, processes of self-organization in nature are considered as computational processes. At the same time, it is emphasized that various computational paradigms for the study of complex patterns are possible: reaction-diffusion computing, collision-based computing, swarm computing, quantum information, fuzzy balanced sets, fractals, nonlinear systems. These approaches allow complex patterns not only to be simulated, but also programmed.
Electromagnetic energy transfer processes in effective electro-magneto dynamics of axions
Authors: Patkós A.
Published: October 2023

Oscillating and dissipative energy exchange between the electromagnetic and axion fields is investigated in an effective electro-magneto dynamical (EEMD) model theory, implying the coexistence of axions with hypothetic magnetic charges. An exact formula is presented for the energy transfer between the electromagnetic and axionic sectors. In a first example, we compute analytically the homogeneously oscillating electric and magnetic field configurations generated by the combined action of a constant static magnetic field and a periodically oscillating axion condensate. In the second example, the electromagnetic radiative energy loss of a gravitationally bound axion configuration is computed in the EEMD model. As a result, an asymptotic [Formula: see text] temporal increase of the clump size is found also in EEMD.
Exploring meandering river cutoffs
Authors: Gao Peng , Li Zhiwei
Published: October 2023

Cutoffs, which include neck and chute cutoffs, are the results of the fluvial processes that fundamentally influence evolution of meandering rivers. A neck cutoff happens when the two limbs of a highly sinuous bend touch, whereas a chute cutoff refers to the formation of a shortcut channel passing through a meander bend. In this review, we begin by distinguishing the morphological and hydrological conditions of the two cutoff types. Mechanisms driving the development of a neck cutoff are embodied in a variety of kinematical and hydrodynamic models simulating processes governing the long-term evolution of meandering rivers. These models adopt a morphological threshold for judging the occurrence of a neck cutoff,
b
=
αw
, where
α
is a constant ranging between 0 and 1,
b
is the bend neck width and
w
is the mean channel width. The potential underestimation of the evolutionary period during the late stage of bend evolution toward a neck cutoff when using this morphological threshold and the uncertainties in quantifying the migration–curvature relationship limit the abilities of existing models to predict the occurrence of neck cutoffs. We then suggest three possible directions for future research on meander neck cutoffs. Mechanisms controlling chute cutoffs are relevant to six key factors representing the meander hydrological regime, planform morphology, bed topography and floodplain characteristics. The combination of these factors gives rise to four distinguishable triggering mechanisms: headward-erosion, embayment, mid-channel bar and scroll–slough chute cutoffs, though the initiation of the chute cutoff may be caused by some combination of these. However, the hydraulic and morphological characteristics of meander bends under these triggering mechanisms are so complex that they are often site-specific, making it extremely challenging to generalize the known morphodynamic and hydrodynamic processes driving the formation of chute cutoffs in individual meander bends. We close the review by recommending three possible research directions on chute cutoffs for tackling the existing challenges in the future.
Computational Thinking and Notional Machines: The Missing Link
Authors: Munasinghe Bhagya , Bell Tim , Robins Anthony
Published: October 2023

In learning to program and understanding how a programming language controls a computer, learners develop both insights and misconceptions whilst their mental models are gradually refined. It is important that the learner is able to distinguish the different elements and roles of a computer (compiler, interpreter, memory, etc.), which novice programmers may find difficult to comprehend. Forming accurate mental models is one of the potential sources of difficulty inextricably linked to mastering computing concepts and processes, and for learning computer programming.

It is common to use some form of representation (e.g., an abstract machine or a Computational Agent (CA)) to support technical or pedagogic explanations. The Notional Machine (NM) is a pedagogical device that entails one or more computational concepts, originally described as an idealised computer operating with the constructs of a particular programming language. It can be used to support specific or general learning goals and will typically have some concrete representation that can be referred to. Computational Thinking (CT), which is defined as a way of thinking that is used for [computational] problem solving, is often presented as using a CA to carry out information processing presented by a solution.

In CT, where the typical goal is to produce an algorithm or a computer program, the CA seemingly serves a purpose very similar to an NM. Although it changes through the different stages of development (of the learner and of the curriculum), the roles of CAs and NMs can be seen as versatile tools that connect a learner’s mental model with the conceptual model of a program. In this article, we look at this relationship between CAs and NMs, and indicate how they would look at different stages of learning. We traverse the range of definitions and usages of these concepts, and articulate models that clarify how these are viewed in the literature. This includes exploring the nature of machines and agents, and how historical views of these relate to modern pedagogy for computation. We argue that the CA can be seen as an abstract, simplified variant of an NM that provides a useful perspective to the learner to support them to form robust mental models of NMs more efficiently and effectively. We propose that teaching programming should make use of the idea of a CA at different stages of learning, as a link that connects a learner’s mental model to a full NM.
A Rapid Test Method Based on Prediction with Swarm Intelligent Optimization and Monte Carlo Expansion for Lithium-Ion Battery Cycle Life
Authors: Zhu Yuhao , Gu Xin , Mao Ziheng , Zhao Wenyuan , Shang Yunlong
Published: October 2023

The cycle life test offers significant sustainment for utilization and maintenance of lithium-ion batteries. The traditional way is continuous charge-discharge testing without interruption, which often takes one year or even longer. Therefore, this paper proposes a rapid cycle life test method based on intelligent prediction to replace the continuous test, which shortens the test period and accelerates product replacement. The original capacity data is decoupled into the short-term regeneration trajectory and the long-term degradation trajectory, which are predicted by the long-short term memory model optimized by swarm intelligent algorithm. The data expansion technique based on Monte Carlo sampling is used to increase the diversity of training data to improve the prediction accuracy. The feasibility and effectiveness are proved by NASA data sets. The results show that the cycle life test time reduced by at least 90% with the error less than 3 cycles.
Cognitive Dysfunction in Patients Treated with Androgen Deprivation Therapy: A Multimodality Functional Imaging Study to Evaluate Neuroinflammation
Authors: Saleem Azeem , Shah Syed Imran Ali , Mangar Stephen A. , Coello Christopher , Wall Matthew B. , Rizzo Gaia , Jones Terry , Price Patricia M.
Published: October 2023

Background. Androgen deprivation therapy (ADT) for prostate cancer is implicated as a possible cause of cognitive impairment (CI). CI in dementia and Alzheimer’s disease is associated with neuroinflammation. In this study, we investigated a potential role of neuroinflammation in ADT-related CI. Methods. Patients with prostate cancer on ADT for ≥3 months were categorized as having ADT-emergent CI or normal cognition (NC) based on self-report at interview. Neuroinflammation was evaluated using positron emission tomography (PET) with the translocator protein (TSPO) radioligand [11C]-PBR28. [11C]-PBR28 uptake in various brain regions was quantified as standardized uptake value (SUVR, normalized to cerebellum) and related to blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) choice-reaction time task (CRT) activation maps. Results. Eleven patients underwent PET: four with reported CI (rCI), six with reported NC (rNC), and one status unrecorded. PET did not reveal any between-group differences in SUVR regionally or globally. There was no difference between groups on brain activation to the CRT. Regardless of the reported cognitive status, there was strong correlation between PET-TSPO signal and CRT activation in the hippocampus, amygdala, and medial cortex. Conclusions. We found no difference in neuroinflammation measured by PET-TSPO between patients with rCI and rNC. However, we speculate that the strong correlation between TSPO uptake and BOLD-fMRI activation in brain regions involved in memory and known to have high androgen-receptor expression mediating plasticity (hippocampus and amygdala) might reflect inflammatory effects of ADT with compensatory upregulated/increased synaptic functions. Further studies of this imaging readout are warranted to investigate ADT-related CI.
A Forward Solution Algorithm of 6RUS Parallel Mechanism Based on Dual Quaternion Method
Authors: Dong Guangyu-yu , Du Yu-hong , Li Wen-peng
Published: October 2023

The 6RUS parallel manipulator is a highly versatile and widely used robotic mechanism with six degrees of freedom. Its intricate kinematic structure and its capability to perform complex motion tasks have garnered significant research interest in recent years. The kinematic analysis of the 6RUS mechanism plays a crucial role in understanding its operational characteristics and optimizing its performance for various applications. In this paper, we present a state-of-the-art kinematic algorithm for the 6RUS parallel manipulator. Our algorithm is aimed at addressing the challenges associated with accurately determining the pose and motion of the end-effector relative to the base, considering the complexity of the mechanism’s architecture. By leveraging advanced mathematical modeling techniques and utilizing efficient computational algorithms, our proposed algorithm offers improved accuracy, efficiency, and robustness in determining the kinematic parameters of the 6RUS mechanism. The key contributions of this work include the development of a comprehensive forward and inverse kinematic model for the 6RUS parallel manipulator, incorporating the effects of joint constraints, singularities, and workspace limitations. We also present a detailed analysis of the algorithm’s performance in comparison to existing approaches, demonstrating its superiority in terms of computational efficiency and accuracy. The proposed kinematic algorithm holds significant potential for enhancing the design, control, and trajectory planning of 6RUS parallel manipulators. It provides a solid foundation for advanced applications such as robotic surgery, industrial automation, and virtual reality systems. The results presented in this paper contribute to the growing body of knowledge in parallel manipulator research and pave the way for future developments in the field.
Lenacapavir with Fostemsavir in a Multidrug-Resistant HIV-Infected Hemodialysis Patient
Authors: Bigirimana Ferdinand , Van den Wijngaert Sigi , Fosso Christelle , Stoffels Karolien , Martin Charlotte , Maillart Evelyne , Clevenbergh Philippe
Published: October 2023

We report a hemodialysis MDR HIV-infected patient switched to fostemsavir with lenacapavir plus lamivudine for more than a year. She maintained a suppressed viral replication and did not present any clinical or biological drug-related side effects. The combination of lenacapavir plus fostemsavir looks promising in terms of safety and efficacy even in patients with end-stage renal disease awaiting renal transplant. Both drugs are first in class ARVs so that there is no cross resistance with previous drugs, maintaining their efficacy against MDR HIV.
Irradiation Attenuates Systemic Lupus Erythematosus-Like Morbidity in NZBWF1 Mice: Focusing on CD180-Negative Cells
Authors: Fujita Kazuko , Kuwabara Taku , Wang Bing , Tanaka Kaoru , Ito Kei , Akishima-Fukasawa Yuri , Mikami Tetuo , Akasaka Yoshikiyo , Ishii Toshiharu
Published: October 2023

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies that can induce systemic inflammation. Ultraviolet-A and X-ray irradiation have been reported to have therapeutic effects in patients with SLE. We previously demonstrated that CD180-negative cells, these are radiosensitive, contribute to the development of SLE-like morbidity in NZBWF1 mice. In this study, the effects of irradiation on SLE-like morbidity manifestations in NZBWF1 mice and on CD180-negative cells were investigated. Whole-body irradiation, excluding the head, attenuated SLE-like morbidity in vivo, as indicated by the prevention of the renal lesion development, inhibition of anti-dsDNA antibody production, reduction of urinary protein levels, and prolongation of the lifespan. Irradiation also reduced the proportion of CD180-negative cells in the spleen. Although other immune cells or molecules may be triggered because of the whole-body irradiation treatment, previous research, and the current results suggest a strong relationship between the radiation-induced decrease in CD180-negative cells and the amelioration of SLE-like morbidities. Clinical trials assessing CD180-negative cells as a therapeutic target for SLE have been hampered by the lack of validated cell markers; nonetheless, the present findings suggest that radiotherapy may be a new therapeutic strategy for managing SLE symptoms.
Unlocking the Mysteries of Chromatin Biology through Functional Epigenomics
Authors: Ye Ziyang , Soshnev Alexey A. , Soto-Feliciano Yadira
Published: October 2023

In the ever evolving field of functional genomics, CRISPR-based screening technologies have become pivotal tools for elucidating gene function across various cell types. A recent study by Gilan and colleagues advances this technological frontier by introducing CRISPR-ChIP, a platform designed to investigate the complex dynamics of epigenetic regulation of chromatin. In proof-of-concept experiments, the authors demonstrate the potential of this tool to identify key molecular regulators of two major histone modifications associated with active transcription, H3 lysine 4 trimethylation (H3K4me3) and H3 lysine 79 dimethylation (H3K79me2). They further unveiled a previously unknown functional partitioning of the H3K79-specific methyltransferase DOT1L into an oncogenic complex with MLL-AF9 and a native complex with MLLT10, which cooperatively regulate mixed lineage leukemia fusion protein (MLL-FP) target gene expression. This novel epigenomic approach integrates high-throughput CRISPR screening with chromatin immunoprecipitation–based direct readout of chromatin modifications in situ, offering a powerful tool to investigate the epigenetic regulatory layers across a diverse spectrum of biological processes and disease states.
Intraoperative Integrated Diagnostic System for Malignant Central Nervous System Tumors
Authors: Hayashi Takahiro , Tateishi Kensuke , Matsuyama Shinichiro , Iwashita Hiromichi , Miyake Yohei , Oshima Akito , Honma Hirokuni , Sasame Jo , Takabayashi Katsuhiro , Sugino Kyoka , Hirata Emi , Udaka Naoko , Matsushita Yuko , Kato Ikuma , Hayashi Hiroaki , Nakamura Taishi , Ikegaya Naoki , Takayama Yutaro , Sonoda Masaki , Oka Chihiro , Sato Mitsuru , Isoda Masataka , Kato Miyui , Uchiyama Kaho , Tanaka Tamon , Muramatsu Toshiki , Miyake Shigeta , Suzuki Ryosuke , Takadera Mutsumi , Tatezuki Junya , Ayabe Junichi , Suenaga Jun , Matsunaga Shigeo , Miyahara Kosuke , Manaka Hiroshi , Murata Hidetoshi , Yokoyama Takaakira , Tanaka Yoshihide , Shuto Takashi , Ichimura Koichi , Kato Shingo , Yamanaka Shoji , Cahill Daniel P. , Fujii Satoshi , Shankar Ganesh M. , Yamamoto Tetsuya
Published: October 2023

Purpose:

The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors uses an integrated approach involving histopathology and molecular profiling. Because majority of adult malignant brain tumors are gliomas and primary CNS lymphomas (PCNSL), rapid differentiation of these diseases is required for therapeutic decisions. In addition, diffuse gliomas require molecular information on single-nucleotide variants (SNV), such as IDH1/2. Here, we report an intraoperative integrated diagnostic (i-ID) system to classify CNS malignant tumors, which updates legacy frozen-section (FS) diagnosis through incorporation of a qPCR-based genotyping assay.

Experimental Design:

FS evaluation, including GFAP and CD20 rapid IHC, was performed on adult malignant CNS tumors. PCNSL was diagnosed through positive CD20 and negative GFAP immunostaining. For suspected glioma, genotyping for IDH1/2, TERT SNV, and CDKN2A copy-number alteration was routinely performed, whereas H3F3A and BRAF SNV were assessed for selected cases. i-ID was determined on the basis of the 2021 WHO classification and compared with the permanent integrated diagnosis (p-ID) to assess its reliability.

Results:

After retrospectively analyzing 153 cases, 101 cases were prospectively examined using the i-ID system. Assessment of IDH1/2, TERT, H3F3AK27M, BRAFV600E, and CDKN2A alterations with i-ID and permanent genomic analysis was concordant in 100%, 100%, 100%, 100%, and 96.4%, respectively. Combination with FS and intraoperative genotyping assay improved diagnostic accuracy in gliomas. Overall, i-ID matched with p-ID in 80/82 (97.6%) patients with glioma and 18/19 (94.7%) with PCNSL.

Conclusions:

The i-ID system provides reliable integrated diagnosis of adult malignant CNS tumors.
Quantifying the Expanding Landscape of Clinical Actionability for Patients with Cancer
Authors: Suehnholz Sarah P. , Nissan Moriah H. , Zhang Hongxin , Kundra Ritika , Nandakumar Subhiksha , Lu Calvin , Carrero Stephanie , Dhaneshwar Amanda , Fernandez Nicole , Xu Benjamin W. , Arcila Maria E. , Zehir Ahmet , Syed Aijazuddin , Brannon A. Rose , Rudolph Julia E. , Paraiso Eder , Sabbatini Paul J. , Levine Ross L. , Dogan Ahmet , Gao Jianjiong , Ladanyi Marc , Drilon Alexander , Berger Michael F. , Solit David B. , Schultz Nikolaus , Chakravarty Debyani
Published: October 2023

There is a continuing debate about the proportion of cancer patients that benefit from precision oncology, attributable in part to conflicting views as to which molecular alterations are clinically actionable. To quantify the expansion of clinical actionability since 2017, we annotated 47,271 solid tumors sequenced with the MSK-IMPACT clinical assay using two temporally distinct versions of the OncoKB knowledge base deployed 5 years apart. Between 2017 and 2022, we observed an increase from 8.9% to 31.6% in the fraction of tumors harboring a standard care (level 1 or 2) predictive biomarker of therapy response and an almost halving of tumors carrying nonactionable drivers (44.2% to 22.8%). In tumors with limited or no clinical actionability, TP53 (43.2%), KRAS (19.2%), and CDKN2A (12.2%) were the most frequently altered genes.

Significance:

Although clear progress has been made in expanding the availability of precision oncology-based treatment paradigms, our results suggest a continued unmet need for innovative therapeutic strategies, particularly for cancers with currently undruggable oncogenic drivers.

See related commentary by Horak and Fröhling, p. 18.

This article is featured in Selected Articles from This Issue, p. 5
TABLE 2 from Immune-related Adverse Events after Immune Checkpoint Blockade–based Therapy Are Associated with Improved Survival in Advanced Sarcomas
Authors: Rosenbaum Evan , Seier Kenneth , Bradic Martina , Kelly Ciara , Movva Sujana , Nacev Benjamin A. , Gounder Mrinal M. , Keohan Mary L. , Avutu Viswatej , Chi Ping , Thornton Katherine A. , Chan Jason E. , Dickson Mark A. , Donoghue Mark T.A. , Tap William D. , Qin Li-Xuan , D'Angelo Sandra P.
Published: October 2023

irAEs seen across trials
Supplementary Data from Immune-related Adverse Events after Immune Checkpoint Blockade–based Therapy Are Associated with Improved Survival in Advanced Sarcomas
Authors: Rosenbaum Evan , Seier Kenneth , Bradic Martina , Kelly Ciara , Movva Sujana , Nacev Benjamin A. , Gounder Mrinal M. , Keohan Mary L. , Avutu Viswatej , Chi Ping , Thornton Katherine A. , Chan Jason E. , Dickson Mark A. , Donoghue Mark T.A. , Tap William D. , Qin Li-Xuan , D'Angelo Sandra P.
Published: October 2023

Supplemental Table 1: Histologic subtype of sarcoma sorted by frequency; Supplemental Table 2: Histologic subtype, irAE, and response status of patients included in RNA seq analysis; Supplemental Table 3: GSEA of hallmark pathways by irAE status
Data from Immune-related Adverse Events after Immune Checkpoint Blockade–based Therapy Are Associated with Improved Survival in Advanced Sarcomas
Authors: Rosenbaum Evan , Seier Kenneth , Bradic Martina , Kelly Ciara , Movva Sujana , Nacev Benjamin A. , Gounder Mrinal M. , Keohan Mary L. , Avutu Viswatej , Chi Ping , Thornton Katherine A. , Chan Jason E. , Dickson Mark A. , Donoghue Mark T.A. , Tap William D. , Qin Li-Xuan , D'Angelo Sandra P.
Published: October 2023

Abstract
The association between immune-related AEs (irAE) and outcome in patients with sarcoma is not known. We retrospectively reviewed a cohort of patients with advanced sarcoma treated with immune checkpoint blockade (ICB)-based therapy. Association of irAEs with survival was assessed using a Cox regression model that incorporated irAE occurrence as a time-dependent covariate. Tumor samples with available RNA sequencing data were stratified by presence of an irAE to identify patterns of differential gene expression. A total of 131 patients were included. Forty-two (32%) had at least one irAE of any grade and 16 (12%) had at least one grade ≥ 3 irAE. The most common irAEs were hypothyroidism (8.3%), arthralgias (5.3%), pneumonitis (4.6%), allergic reaction (3.8%), and elevated transaminases (3.8%). Median progression-free survival (PFS) and overall survival (OS) from the time of study entry were 11.4 [95% confidence interval (CI), 10.7–15.0) and 74.6 weeks (CI, 44.9–89.7), respectively. On Cox analysis adjusting for clinical covariates that were significant in the univariate setting, the HR for an irAE (HR, 0.662; CI, 0.421–1.041) approached, but did not reach statistical significance for PFS (P = 0.074). Patients had a significantly lower HR for OS (HR, 0.443; CI, 0.246–0.798; P = 0.007) compared with those without or before an irAE. Gene expression profiling on baseline tumor samples found that patients who had an irAE had higher numbers of tumor-infiltrating dendritic cells, CD8+ T cells, and regulatory T cells as well as upregulation of immune and inflammatory pathways.
Significance:
irAE after ICB therapy was associated with an improved OS; it also approached statistical significance for improved PFS. Patients who had an irAE were more likely to have an inflamed tumor microenvironment at baseline.