bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep Learning for Continuous-Time Leader Synchronization in Graphical Games Using Sampling and Deep Neural Networks
Authors: Zhang Da , Anwar Junaid , Rizvi Syed Ali Asad , Wei Yusheng 
Published: October 2023

Abstract
We propose a novel deep learning-based approach for the problem of continuous-time leader synchronization in graphical games on large networks. The problem setup is to deploy a distributed and coordinated swarm to track the trajectory of a leader while minimizing local neighborhood tracking error and control costs for each agent. The goal of our work is to develop optimal control policies for continuous-time leader synchronization in graphical games using deep neural networks. We discretize the agents model using sampling to facilitate the modification of gradient descent methods for learning optimal control policies. The distributed swarm is deployed for a certain amount of time while keeping the control input of each agent constant during each sampling period. After collecting state and input data at each sampling time during one iteration, we update the weights of a deep neural network for each agent using collected data to minimize a loss function that characterizes the agents' local neighborhood tracking error and the control cost. A modified gradient descent method is presented to overcome existing limitations. The performance of the proposed method is compared with two reinforcement learning-based methods in terms of robustness to initial neural network weights and initial local neighborhood tracking errors and the scalability to networks with a large number of agents. Our approach has been shown to achieve superior performance compared with the other two methods.
Supercapacitors Based on Spider Nest–Shaped Nickel Foam Electrodes Operating in Seawater
Authors: Li Haiying , Hui Yuchen , Xia Zunbin , Wang Huixin 
Published: October 2023

Abstract
An environmental-friendly supercapacitor based on aqueous electrolyte was fabricated. Electrodes with conductive spider nest–shaped three-dimensional (3D) porous structures were prepared for the assembly of symmetric supercapacitors. The nickel foam was modified by multiwalled carbon nanotubes and β-cyclodextrin. The construction of the spider nest was stabilized via the chemical bond inside carbon nanotubes, π–π stack effects among carbon nanotubes, and physical adsorption between nickel foam and carbon nanotubes substrate. The role of β-cyclodextrin is a dispersant to prevent agglomeration of carbon nanotubes, thereby enhancing electroactive surface area of nickel foam and improving the specific capacitance of the electrodes. Furthermore, the electrodes exhibited excellent rate capability. The obtained symmetrical supercapacitors exhibited an excellent power density of 17,561.3 W kg−1, a good specific capacitance of 398.8 F g−1, and an energy density of 154.8 Wh kg−1 for 4000 cycles with outstanding cycling stability. In addition, the specific capacitance, energy density, and power density of the supercapacitor operating in seawater were found to be 100.2 F g−1, 17.8 Wh kg−1, and 2568 Wh kg−1, respectively, for 3000 cycles. Overall, our findings indicate that the supercapacitor could stably operate in seawater and shows potential for use as an ecofriendly power supply to marine engineering equipment.
Gene recoding by synonymous mutations creates promiscuous intragenic transcription initiation in mycobacteria
Authors: Hegelmeyer Nuri K. , Parkin Lia A. , Previti Mary L. , Andrade Joshua , Utama Raditya , Sejour Richard J. , Gardin Justin , Muller Stephanie , Ketchum Steven , Yurovsky Alisa , Futcher Bruce , Goodwin Sara , Ueberheide Beatrix , Seeliger Jessica C. 
Published: October 2023

ABSTRACT

Each genome encodes some codons more frequently than their synonyms (codon usage bias), but codons are also arranged more frequently into specific pairs (codon pair bias). Recoding viral genomes and yeast or bacterial genes with non-optimal codon pairs has been shown to decrease gene expression. Gene expression is thus importantly regulated not only by the use of particular codons but also by their proper juxtaposition. We therefore hypothesized that non-optimal codon pairing could likewise attenuate
Mycobacterium tuberculosis
(
Mtb
) genes. We explored the role of codon pair bias by recoding
Mtb
genes (
rpoB, mmpL3
, and
ndh
) and assessing their expression in the closely related and tractable model organism
M. smegmatis
. To our surprise, recoding caused the expression of multiple smaller protein isoforms from all three genes. We confirmed that these smaller proteins were not due to protein degradation but instead issued from new transcription initiation sites positioned within the open reading frame. New transcripts gave rise to intragenic translation initiation sites, which, in turn, led to the expression of smaller proteins. We next identified the nucleotide changes associated with these new sites of transcription and translation. Our results demonstrated that apparently benign, synonymous changes can drastically alter gene expression in mycobacteria. More generally, our work expands our understanding of the codon-level parameters that control translation and transcription initiation.

IMPORTANCE

Mycobacterium tuberculosis
(
Mtb
) is the causative agent of tuberculosis, one of the deadliest infectious diseases worldwide. Previous studies have established that synonymous recoding to introduce rare codon pairings can attenuate viral pathogens. We hypothesized that non-optimal codon pairing could be an effective strategy for attenuating gene expression to create a live vaccine for
Mtb
. We instead discovered that these synonymous changes enabled the transcription of functional mRNA that initiated in the middle of the open reading frame and from which many smaller protein products were expressed. To our knowledge, this is one of the first reports that synonymous recoding of a gene in any organism can create or induce intragenic transcription start sites.
Ex-chitin-g news on drug-induced fungal epitope unmasking
Authors: Wheeler Robert T. 
Published: October 2023

ABSTRACT

The microbial cell wall is an essential cellular organelle commonly targeted by antimicrobials. It is also a battleground of innate immune recognition where microbes can evade immune recognition by masking essential cell wall components. A recent study (A. S. Wagner, S. W. Lumsdaine, M. M. Mangrum, and T. B. Reynolds, mBio
https://doi.org/10.1128/mbio.00074-23
, 2023) provides insight into how echinocandin antifungals cause exposure of proinflammatory β(1,3)-glucan by driving excess chitin production in the weakened cell wall. Although many environmental and biological activities perturb cell wall integrity and regulate β(1,3)-glucan exposure, we still know little about which intracellular signaling components regulate the cell wall changes that result in disrupted cell wall architecture. Wagner et al. showed that calcineurin and the Mkc1p kinase regulate chitin deposition and β(1,3)-glucan unmasking. They further identified chitin synthesis as a key driving force in cell wall structure disruption leading to epitope exposure. Their findings highlight how fungal cell wall dynamics have important implications for antifungal immunity and future drug development.
Complete genome sequence of multi-drug-resistant
Salmonella enterica
subsp.
enterica
serovar Typhimurium strain Bnaya isolated from a dairy calf in Israel
Authors: Davidovich Chagai , Awwad Aya , Fleker Marcelo , Weisblit Limor , Cytryn Eddie , Blum Shlomo E. 
Published: October 2023

ABSTRACT

This manuscript reports the complete genome sequence of a
Salmonella enterica
subsp.
enterica
serovar Typhimurium strain (designated “Bnaya”), isolated from a dead dairy calf with severe diarrhea in Israel. The isolate exhibited multi-drug resistance, which is highly unusual in bovine
Salmonella
spp. in Israel, prompting further investigation.
Leveraging existing 16S rRNA microbial data to identify diagnostic biomarker in Chinese patients with gastric cancer: a systematic meta-analysis
Authors: Chen Jijun , Nie Siru , Qiu Xunan , Zheng Shuwen , Ni Chuxuan , Yuan Yuan , Gong Yuehua 
Published: October 2023

ABSTRACT

Gastric cancer is the second most prevalent and deadly cancer in China. Microbiota play an important role in gastric tumorigenesis. However, the available microbial marker studies for gastric cancer do not have consistent results. We searched PubMed for 16S rRNA sequencing in relevant literature on Chinese patients from 1 January 2005 to 18 July 2022, and 16 original articles were finally obtained. Alpha diversity, beta diversity, and bacterial taxa were used to explore the differences in gastric microbiota. Linear discriminant analysis of effect size and a random forest model were used to find the combination of genera with the best diagnostic efficacy.
Streptococcus
,
Pseudomonas
,
Fusobacterium
,
Selenomonas
,
Peptostreptococcus
, and
Prevotella
showed significant differences between gastric cancer and non-gastric cancer, but a single genus performed poorly in identifying patients with gastric cancer. However, a combination of genera
Streptococcus
,
Peptostreptococcus
,
Selenomonas
,
Pseudomonas
, and
Prevotella
had excellent performance in screening gastric cancer with the median area under the curve values of 0.7525 (range: 0.5859–0.9350), 0.8818 (range: 0.7397–0.9533), and 0.7435 (range: 0.7131–0.8483) in the Matched, Unmatched, and Other groups, respectively. Therefore, the results indicated that this combination of genera has good diagnostic efficacy and wide applicability for patients with gastric cancer, which may provide new clues for the non-invasive diagnosis of gastric cancer.

Importance
Gastric cancer is a significant and growing health problem in China. Studies have revealed significant differences in gastric microbiota between patients with gastric cancer and non-cancerous patients, suggesting that microbiota may play a role in tumorigenesis. In this meta-analysis, existing 16S rRNA microbial data were analyzed to find combinations consisting of five genera, which had good efficacy in distinguishing gastric cancer from non-cancerous patients in multiple types of samples. These results lend support to the use of microbial markers in detecting gastric cancer. Moreover, these biomarkers are plausible candidates for further mechanistic research into the role of the microbiota in tumorigenesis.
Abuse, neglect and neurodevelopment across the life course: what can paediatricians and child psychiatrists do about this together? The Illingworth-Rees keynote lecture 2023
Authors: Minnis Helen 
Published: October 2023

Paediatricians and child psychiatrists share complex cases, often associated with abuse, neglect and other ‘Adverse Childhood Experiences (ACEs)’. ACEs are associated in a dose-response relationship with both mental and physical health problems across the life span. We found that 9-year-old children who had been abused and neglected were much more likely to also have symptoms of heritable neurodevelopmental conditions (NDCs) such as ADHD, autism and intellectual disabilities. To our surprise, these were not caused by the abuse and neglect. Instead, both the NDCs and the abuse and neglect were being caused by additional genetic factors. We also found that children who have experienced abuse and neglect, and who also have NDCs, are at twice the risk of developing symptoms of severe mental illness in adolescence. This has caused us to develop our ‘Double Jeopardy’ hypothesis—that experiencing both abuse and neglect and NDCs in childhood might double the risk of a range of physical and mental health problems across the life span.Both paediatricians and child psychiatrists will be faced with children who have complex problems, and they will sometimes need to work together to solve these—whether or not abuse or neglect is in the mix.Dr Corinne Rees’s words were prescient: ‘The truth that psychological issues and behaviour are integral to all illness indicates the necessity for every doctor to feel competent in considering their relevance’. As paediatricians and child psychiatrists, let’s move forward together to overcome the mind-body dichotomy for the benefit of our patients.
Orthopaedic Out of Bed Project (OOBP): improving early mobilisation following femoral fracture using a therapy-led education programme
Authors: Gray Rene , Taylor Melissa , Bullock Ryan 
Published: October 2023

Delayed mobilisation following hip fracture surgery is detrimental to patients and health systems. Prolonged hospital stay additionally results in decreased function and increased mortality. Our hospital was underperforming against the national metric for mobilisation by the day after surgery and physiotherapists were the primary healthcare professionals expected to do this. The therapy team therefore undertook a service improvement to increase the number of patients mobilised by the day after their femoral fracture surgery. This was through a ward-based education programme aimed at increasing confidence and competence of the trauma ward healthcare assistants (HCAs) to complete this task when appropriate instead of physiotherapists.The model for improvement was used, with two Plan-Do-See-Act cycles completed between 2020 and 2022. On completion of the therapy-led intervention, the percentage of patients mobilised by the day after surgery was shown to have increased from a mean average of 60% in 2019 to 79% in 2022. The number of patients mobilised by HCAs prior to physiotherapy assessment increased from 2% prior to and 30% following the intervention.The programme improved HCA confidence and competence using a rehabilitation ethos to mobilise patients following hip fracture surgery. It also showed a clinically significant improvement in the percentage of patients with hip fracture mobilising by the day after surgery and a large increase in the number of patients mobilised by our trauma ward HCAs prior to an initial physiotherapy assessment. This work has demonstrated implications for orthopaedic trauma services and the patients who receive them. It reduces the single point of failure of relying on a physiotherapist to mobilise a patient through increasing multidisciplinary confidence and capability on the ward to perform the task. In turn, this increases physiotherapy capacity to provide acute rehabilitation, which is another important part of femoral fracture recovery.
Quality improvement initiative: implementing routine vertebral fracture assessments into an Australian Fracture Liaison Service
Authors: Greene Leanne , Shah Deval , Laver Kate , Holton Kirrily , Manuel Kisani , Bajger Bogda 
Published: October 2023

Osteoporosis is a global health concern and a major contributor to worldwide mortality rates. Vertebral fractures due to osteoporosis are common and often undetected. Since vertebral fractures are often missed, evidence and guidelines suggest that vertebral fracture assessment (VFA) may optimise current approaches to bone density tests. We aimed to integrate VFA into an Australian Fracture Liaison Service (FLS) and measure the impact it had on osteoporosis treatment initiation.A retrospective case note review was undertaken to determine the number of clinic patients receiving VFA before the change in practice. Proctor’s seven domains of implementation strategy were used to facilitate quality improvement outcomes.The percentage of eligible patients receiving a routine VFA at the FLS imaging centre increased from 0% to 90%. The remaining 10% of patients did not receive a scan due to the patient not being able to assume the correct position, skilled staff being unavailable to perform the scan, or the patient declining. Post implementation, almost half (41%) of patients who underwent a VFA displayed abnormalities and 16 (4%) of these recorded a normal bone measure density score but abnormal VFA. Despite the successful adoption of the new screening protocol, there was no statistically significant increase in treatment initiation rates for patients with normal bone mass density scores.The FLS successfully integrated routine VFA into the osteoporosis care pathway. However, the introduction of VFA did not significantly increase treatment initiation. It may be more effective to offer VFAs to a proportion of patients based on a tailored approach rather than offering them routinely to all patients who access the FLS.
Gluon radiation from a classical point particle: recoil effects
Authors: Kolbé Isobel , Lushozi Mawande 
Published: October 2023

AbstractThe gluon radiation spectrum of a classical particle struck by a sheet of colored glass, is a key ingredient in understanding the distribution of energy and baryon density in the fragmentation region, particularly in the initial stages of heavy ion collisions. However, the currently known classical spectrum has a troublesome high-momentum tail (Kajantie et al. in Phys. Rev. D 100(5):054011, 2019; Phys Rev D 101(5):054012, 2020). By comparing tree-level bremsstrahlung of a spin-less quark to the above-mentioned known result, we propose an interpolating formula that takes into account the recoil of the struck particle, and therefore produces the correct perturbative behaviour at high momentum of the radiated gluon.
Intratumoral Delivery of Chimeric Antigen Receptor T Cells Targeting CD133 Effectively Treats Brain Metastases
Authors: Kieliszek Agata M. , Mobilio Daniel , Upreti Deepak , Bloemberg Darin , Escudero Laura , Kwiecien Jacek M. , Alizada Zahra , Zhai Kui , Ang Patrick , Chafe Shawn C. , Vora Parvez , Venugopal Chitra , Singh Sheila K. 
Published: October 2023

Abstract

Purpose:
Brain metastases (BM) are mainly treated palliatively with an expected survival of less than 12 months after diagnosis. In many solid tumors, the human neural stem cell marker glycoprotein CD133 is a marker of a tumor-initiating cell population that contributes to therapy resistance, relapse, and metastasis.

Experimental Design:
Here, we use a variant of our previously described CD133 binder to generate second-generation CD133-specific chimeric antigen receptor T cells (CAR-T) to demonstrate its specificity and efficacy against multiple patient-derived BM cell lines with variable CD133 antigen expression.

Results:
Using both lung- and colon-BM patient-derived xenograft models, we show that a CD133-targeting CAR-T cell therapy can evoke significant tumor reduction and survival advantage after a single dose, with complete remission observed in the colon-BM model.

Conclusions:
In summary, these data suggest that CD133 plays a critical role in fueling the growth of BM, and immunotherapeutic targeting of this cell population is a feasible strategy to control the outgrowth of BM tumors that are otherwise limited to palliative care.
See related commentary by Sloan et al., p. 477
Potential of Fecal Microbiota Transplantation to Prevent Acute GVHD: Analysis from a Phase II Trial
Authors: Rashidi Armin , Ebadi Maryam , Rehman Tauseef Ur , Elhusseini Heba , Kazadi David , Halaweish Hossam , Khan Mohammad H. , Hoeschen Andrea , Cao Qing , Luo Xianghua , Kabage Amanda J. , Lopez Sharon , Holtan Shernan G. , Weisdorf Daniel J. , Khoruts Alexander , Staley Christopher 
Published: October 2023

Abstract

Purpose:
Intestinal microbiota disruptions early after allogeneic hematopoietic cell transplantation have been associated with increased risk for acute GVHD (aGVHD). In our recent randomized phase II trial of oral, encapsulated, third-party fecal microbiota transplantation (FMT) versus placebo, FMT at the time of neutrophil recovery was safe and ameliorated dysbiosis. Here, we evaluated in post hoc analysis whether donor microbiota engraftment after FMT may protect against aGVHD.

Experimental Design:
We analyzed pre- and post-FMT stool samples and estimated donor microbiota engraftment (a preplanned secondary endpoint) by determining the fraction of post-FMT microbiota formed by unique donor taxa (donor microbiota fraction; dMf).

Results:
dMf was higher in patients who later developed grade I or no aGVHD (median 33.9%; range, 1.6%–74.3%) than those who developed grade II–IV aGVHD (median 25.3%; range, 2.2%–34.8%; P = 0.006). The cumulative incidence of grade II–IV aGVHD by day 180 was lower in the group with greater-than-median dMf than the group with less-than-median dMf [14.3% (95% confidence interval, CI, 2.1–37.5) vs. 76.9% (95% CI, 39.7–92.8), P = 0.008]. The only determinant of dMf in cross-validated least absolute shrinkage and selection operator (LASSO)-regularized regression was the patient's pre-FMT microbiota diversity (Pearson correlation coefficient −0.82, P = 1.6 × 10−9), indicating more potent microbiota modulation by FMT in patients with more severe dysbiosis. Microbiota network analysis revealed major rewiring including changes in the most central nodes, without emergence of keystone species, as a potential mechanism of FMT effect.

Conclusions:
FMT may have protective effects against aGVHD, especially in patients with more severe microbiota disruptions.
Development of a Novel CLDN18.2-directed Monoclonal Antibody and Antibody–Drug Conjugate for Treatment of CLDN18.2-Positive Cancers
Authors: O'Brien Neil A. , McDermott Martina S.J. , Zhang Jun , Gong Ke Wei , Lu Ming , Hoffstrom Benjamin , Luo Tong , Ayala Raul , Chau Kevin , Liang Min , Madrid Athena M. , Donahue Timothy R. , Glaspy John A. , Presta Leonard , Slamon Dennis J. 
Published: October 2023

Abstract
Gastric and pancreatic cancers are malignancies of high unmet clinical need. Expression of CLDN18.2 in these cancers, coupled with it's absence from most normal tissues, provides a potential therapeutic window against this target. We present preclinical development and characterization of a novel therapeutic mAb and antibody–drug conjugate (ADC) targeting CLDN18.2. A humanized CLDN18.2 specific mAb, CLDN18.2-307-mAb, was generated through immunization in mice followed by full humanization of the mouse mAb sequences. Antibody clones were screened by flow cytometry for selective binding to membrane bound CLDN18.2. A CLDN18.2-directed ADC (CLDN18.2–307-ADC) was also generated by conjugating MMAE to CLDN18.2 mAb using a cleavable linker. Tissue expression of CLDN18.2 was determined by IHC assay using a CLDN18.2-specific mAb. CLDN18.2-307-mAb binds with high affinity to CLDN18.2-positive (CLDN18.2+) cells and induces antibody-dependent cell-mediated cytotoxicity (ADCC). Treatment with this CLDN18.2-mAb blocked the growth of CLDN18.2+ gastric and pancreas cancer cell line xenograft (CDX) models. Upon binding to the extracellular domain of this target, the CLDN18.2-ADC/CLDN18.2 protein was internalized and subsequently localized to the lysosomal compartment inducing complete and sustained tumor regressions in CLDN18.2+ CDXs and patient-derived pancreatic cancer xenografts (PDX). A screen of human cancer tissues, by IHC, found 58% of gastric, 60% of gastroesophageal junction, and 20% of pancreatic adenocarcinomas to be positive for membrane expression of CLDN18.2. These data support clinical development of the CLDN18.2-307-mAb and CLDN18.2-307-ADC for treatment of CLDN18.2+ cancers. Both are now being investigated in phase I clinical studies.