bluuebunny/crossref_metadata_2025 huggingface dataset:
Using RNA sequencing to unravel molecular changes underlying the defense response in chickpea induced by Phytophthora medicaginis
Authors: Amalraj Amritha , Baumann Ute , Hayes Julie E. , Sutton Tim
Published: July 2024

Phytophthora root rot (PRR), caused by Phytophthora medicaginis, is a major soil‐borne disease of chickpea in Australia. Breeding for PRR resistance is an effective approach to avoid significant yield loss. Genetic resistance has been identified in cultivated chickpea (Cicer arietinum) and in the wild relative C. echinospermum, with previous studies identifying independent genetic loci associated with each of these sources. However, the molecular mechanisms associated with PRR resistance are not known. RNA sequencing analysis employed in this study identified changes in gene expression in roots of three chickpea genotypes grown hydroponically, early post‐infection with P. medicaginis zoospores. Analyses of differentially expressed genes (DEG) identified the activation of a higher number of non‐specific R‐genes in a PRR‐susceptible variety than in the resistant genotypes, suggesting a whole plant resistance response occurring in chickpea against the pathogen. Contrasting molecular changes in signaling profiles, proteolysis and transcription factor pathways were observed in the cultivated and wild Cicer‐derived resistant genotypes. DEG patterns supported a hypothesis that increased root elongation and reduced adventitious root formation limit the pathogen entry points in the genotype containing the wild Cicer source of PRR resistance. Candidate resistance genes, including an aquaporin and a maltose transporter in the wild Cicer source and GDSL esterases/lipases in the cultivated source of resistance, were oppositely regulated. Increased knowledge of these genes and pathways will improve our understanding of molecular mechanisms controlling PRR resistance in chickpea, and support the development of elite chickpea varieties through molecular breeding approaches.
Diagnostic measures for monitoring and follow‐up in periodontology and implant dentistry
Authors: Ramseier Christoph A.
Published: July 2024

This review discusses the role of diagnostic measures in the lifelong management of periodontal disease and peri‐implant complications. After active treatment, these conditions require regular monitoring of the supporting structures of teeth and dental implants to assess bone and soft tissue health over time. Several clinical measures have been developed for the routine assessment of periodontal and peri‐implant tissues, including periodontal and peri‐implant probing, bleeding on probing, intraoral radiography, biomarker analysis, and microbiological testing. This review highlights the evolution of diagnostic practices, integrating traditional methods with emerging technologies such as resonance frequency analysis and ultrasound imaging to provide a holistic view of peri‐implant health assessment. In addition to objective measurements, patient risk factors are considered. The goals of periodontal and peri‐implant maintenance are to control disease activity and stabilize tissues through supportive care, which includes diagnostic measures at follow‐up visits. This enables clinicians to monitor treatment outcomes, assess health status, and detect recurrence or progression early through routine evaluation, allowing additional interventions, including adjustment of supportive therapy intervals, to further improve and maintain periodontal and peri‐implant stability over time.
Suppression of excitatory synaptic transmission in the centrolateral amygdala via presynaptic histamine H3 heteroreceptors
Authors: Zhang Bei‐Bei , Ling Xin‐Yu , Shen Qing‐Yi , Zhang Yang‐Xun , Li Qian‐Xiao , Xie Shu‐Tao , Li Hong‐Zhao , Zhang Qi‐Peng , Yung Wing‐Ho , Wang Jian‐Jun , Ke Ya , Zhang Xiao‐Yang , Zhu Jing‐Ning
Published: July 2024

The central histaminergic system has a pivotal role in emotional regulation and psychiatric disorders, including anxiety, depression and schizophrenia. However, the effect of histamine on neuronal activity of the centrolateral amygdala (CeL), an essential node for fear and anxiety processing, remains unknown. Here, using immunostaining and whole‐cell patch clamp recording combined with optogenetic manipulation of histaminergic terminals in CeL slices prepared from histidine decarboxylase (HDC)‐Cre rats, we show that histamine selectively suppresses excitatory synaptic transmissions, including glutamatergic transmission from the basolateral amygdala, on both PKC‐δ‐ and SOM‐positive CeL neurons. The histamine‐induced effect is mediated by H3 receptors expressed on VGLUT1‐/VGLUT2‐positive presynaptic terminals in CeL. Furthermore, optoactivation of histaminergic afferent terminals from the hypothalamic tuberomammillary nucleus (TMN) also significantly suppresses glutamatergic transmissions in CeL via H3 receptors. Histamine neither modulates inhibitory synaptic transmission by presynaptic H3 receptors nor directly excites CeL neurons by postsynaptic H1, H2 or H4 receptors. These results suggest that histaminergic afferent inputs and presynaptic H3 heteroreceptors may hold a critical position in balancing excitatory and inhibitory synaptic transmissions in CeL by selective modulation of glutamatergic drive, which may not only account for the pathophysiology of psychiatric disorders but also provide potential psychotherapeutic targets.

image

Key points

Histamine selectively suppresses the excitatory, rather than inhibitory, synaptic transmissions on both PKC‐δ‐ and SOM‐positive neurons in the centrolateral amygdala (CeL).

H3 receptors expressed on VGLUT1‐ or VGLUT2‐positive afferent terminals mediate the suppression of histamine on glutamatergic synaptic transmission in CeL.

Optogenetic activation of hypothalamic tuberomammillary nucleus (TMN)–CeL histaminergic projections inhibits glutamatergic transmission in CeL via H3 receptors.
Measurement of Laminar Burning Speed of Methane/Hydrogen/Air Mixtures at High Pressures and Temperatures
Authors: Lu Zhenyu , Zhang Yusheng , Metghalchi Hameed
Published: July 2024

Green hydrogen which could be produced from renewable sources by solar water splitting or photovoltaic electrolysis will play an important role in achieving net-zero in the near future. One possible approach will be to mix hydrogen with natural gas for power generation in gas turbine systems. It is necessary to know the physical properties of burning speed of the mixture of natural gas and hydrogen. Since natural gas is mainly made up of methane, the burning speed of mixtures of methane and hydrogen has been measured and reported in this paper. Adding hydrogen gas during the combustion of methane enhances flame stability, expands the lean flammability range, decreases pollutant emissions, and boosts the burning speed. Burning speed measurement is performed in a cylindrical and spherical chamber. The pressure rise due to combustion was measured by a pressure transducer on the top of cylindrical and spherical chambers. The Z-shaped Schlieren system, equipped with a high-speed complementary metal oxide semiconductor (CMOS) camera, obtains pictures of flame propagation. Laminar burning speed is measured exclusively for flames that have a smooth and spherical shape. In addition, burning speed is only measured for large flame radii with low stretch rates. Burning speed is calculated by a thermodynamic model with the pressure rise data as an input. Measurements cover a wide range of operating conditions. The hydrogen mole fraction is 0%, 20%, and 40%, with temperatures of 298–400 K, pressures between 0.5 and 5.5 atmospheres and equivalence ratios of 0.8, 1, and 1.2.
A Curved Surface Integral Method for Reliability Analysis of Multiple Failure Modes System With Nonoverlapping Failure Domains
Authors: Chen Zhenzhong , Mu Haoxun , Li Xiaoke
Published: July 2024

In the study of reliability of systems with multiple failure modes, approximations can be obtained by calculating the probability of failure for each state function. The first-order reliability method and the second-order reliability method are effective, but they may introduce significant errors when dealing with certain nonlinear situations. Simulation methods such as line sampling method and response surface method can solve implicit function problems, but the large amount of calculation results in low efficiency. The curved surface integral method (CSI) has good accuracy in dealing with nonlinear problems. Therefore, a system reliability analysis method (CSIMMS) is proposed on the basis of CSI for solving multiple failure modes system reliability problems with nonoverlapping failure domains. The order of magnitude of the failure probability is evaluated based on the reliability index and the degree of nonlinearity, ignoring the influence of low order of magnitude failure modes, and reducing the calculation of the system failure probability. Finally, CSIMMS and other methods are compared with three numerical examples, and the results show the stability and accuracy of the proposed method.
Engineered mini-G proteins block the internalization of cognate GPCRs and disrupt downstream intracellular signaling
Authors: Manchanda Yusman , ElEid Liliane , Oqua Affiong I. , Ramchunder Zenouska , Choi Jiyoon , Shchepinova Maria M. , Rutter Guy A. , Inoue Asuka , Tate Edward W. , Jones Ben , Tomas Alejandra
Published: July 2024

Mini-G proteins are engineered, thermostable variants of Gα subunits designed to stabilize G protein–coupled receptors (GPCRs) in their active conformations. Because of their small size and ease of use, they are popular tools for assessing GPCR behaviors in cells, both as reporters of receptor coupling to Gα subtypes and for cellular assays to quantify compartmentalized signaling at various subcellular locations. Here, we report that overexpression of mini-G proteins with their cognate GPCRs disrupted GPCR endocytic trafficking and associated intracellular signaling. In cells expressing the Gα
s
-coupled GPCR glucagon-like peptide 1 receptor (GLP-1R), coexpression of mini-G
s
, a mini-G protein derived from Gα
s
, blocked β-arrestin 2 recruitment and receptor internalization and disrupted endosomal GLP-1R signaling. These effects did not involve changes in receptor phosphorylation or lipid nanodomain segregation. Moreover, we found that mini-G proteins derived from Gα
i
and Gα
q
also inhibited the internalization of GPCRs that couple to them. Finally, we developed an alternative intracellular signaling assay for GLP-1R using a nanobody specific for active Gα
s
:GPCR complexes (Nb37) that did not affect GLP-1R internalization. Our results have important implications for designing methods to assess intracellular GPCR signaling.
Microbiological survey and genomic analysis of
Cronobacter sakazakii
strains isolated from US households and retail foods
Authors: Samadpour Mansour , Benoit Lora , Myoda Sam , Hans Bada , Nadala Cesar , Kim Seong Hong , Themeli Eni , Cantera Ruth , Nguyen Truyen , Richter Hans
Published: July 2024

Cronobacter
species are opportunistic pathogens that are capable of causing morbidity and mortality, particularly in infants. Although the transmission dynamics involved in
Cronobacter
infections remain largely unknown, contaminated powdered infant formula (PIF) has been linked to 30% of
Cronobacter sakazakii
cases involving invasive illness in infants. As several lines of evidence have implicated the domestic environment in PIF contamination, we undertook a microbiological survey of homes (
N
= 263) across the US.
Cronobacter
spp. and
C. sakazakii
were isolated from 36.1% and 24.7% of US homes, respectively, with higher recovery rates observed for floor and kitchen surfaces. Multi-locus sequence typing indicated that the dominant strain was
C. sakazakii
ST4, the sequence type most commonly associated with neonatal meningitis. For comparison purposes, retail foods (
N
= 4,009) were also surveyed, with the highest contamination frequencies (10.1%–26.3%) seen for nut products, seeds, and grains/baked goods/flours. The sequence type profile of isolates recovered from homes mirrored that of isolates recovered from retail foods, with increased representation of ST1, ST4, ST13, ST17, and ST40. Analysis of 386 whole genomic sequences revealed significant diversity. Redundancies were only observed for isolates recovered from within the same domicile, and there were no identical matches with sequences archived at the NCBI pathogen database. Genes coding for putative virulence and antibiotic resistance factors did not segregate with clinically significant sequence types. Collectively, these findings support the possibility that contamination events occurring within the home should not be overlooked as a contributor to community-onset
Cronobacter
infections.

IMPORTANCE

Cronobacter sakazakii
is an opportunistic pathogen that can cause significant morbidity and mortality in neonates. Its transmission dynamics are poorly understood, though powered infant formula (PIF) is thought to be the major transmission vehicle. How the PIF becomes contaminated remains unknown. Our survey shows that roughly 1/4 of US homes are contaminated with
Cronobacter sakazakii
, particularly in the kitchen setting. Our analyses suggest that the domestic environment may contribute to contamination of PIF and provides insights into mitigating the risk of transmission.
Mucor germinans,
a novel dimorphic species resembling
Paracoccidioides
in a clinical sample: questions on ecological strategy
Authors: Li Na , Bowling Jennifer , de Hoog Sybren , Aneke Chioma I. , Youn Jung-Ho , Shahegh Sherin , Cuellar-Rodriguez Jennifer , Kanakry Christopher G. , Rodriguez Pena Maria , Ahmed Sarah A. , Al-Hatmi Abdullah M. S. , Tolooe Ali , Walther Grit , Kwon-Chung Kyung J. , Kang Yingqian , Lee Hyang Burm , Seyedmousavi Amir
Published: July 2024

Dimorphism is known among the etiologic agents of endemic mycoses as well as in filamentous
Mucorales
. Under appropriate thermal conditions, mononuclear yeast forms alternate with multi-nucleate hyphae. Here, we describe a dimorphic mucoralean fungus obtained from the sputum of a patient with Burkitt lymphoma and ongoing graft-versus-host reactions. The fungus is described as
Mucor germinans
sp. nov. Laboratory studies were performed to simulate temperature-dependent dimorphism, with two environmental strains
Mucor circinelloides
and
Mucor kunryangriensis
as controls. Both strains could be induced to form multinucleate arthrospores and subsequent yeast-like cells
in vitro
. Multilateral yeast cells emerge in all three
Mucor species
at elevated temperatures. This morphological transformation appears to occur at body temperature since the yeast-like cells were observed in the lungs of our immunocompromised patient. The microscopic appearance of the yeast-like cells in the clinical samples is easily confused with that of
Paracoccidioides
. The ecological role of yeast forms in
Mucorales
is discussed.

IMPORTANCE

Mucormycosis is a devastating disease with high morbidity and mortality in susceptible patients. Accurate diagnosis is required for timely clinical management since antifungal susceptibility differs between species. Irregular hyphal elements are usually taken as the hallmark of mucormycosis, but here, we show that some species may also produce yeast-like cells, potentially being mistaken for
Candida
or
Paracoccidioides
. We demonstrate that the dimorphic transition is common in
Mucor
species and can be driven by many factors. The multi-nucleate yeast-like cells provide an effective parameter to distinguish mucoralean infections from similar yeast-like species in clinical samples.
Unraveling the role of γδ T cells in the pathogenesis of an oncogenic avian herpesvirus
Authors: Sabsabi Mohammad A. , Kheimar Ahmed , You Yu , von La Roche Dominik , Härtle Sonja , Göbel Thomas W. , von Heyl Theresa , Schusser Benjamin , Kaufer Benedikt B.
Published: July 2024

Marek’s disease virus (MDV) is an oncogenic alphaherpesvirus that causes deadly lymphomas in chickens. In chickens, up to 50% of all peripheral T cells are gamma delta (γδ) T cells. Until now, their role in MDV pathogenesis and tumor formation remains poorly understood. To investigate the role of γδ T cells in MDV pathogenesis, we infected recently generated γδ T cell knockout chickens with very virulent MDV. Strikingly, disease and tumor incidence were highly increased in the absence of γδ T cells, indicating that γδ T cells play an important role in the immune response against MDV. In the absence of γδ T cells, virus replication was drastically increased in the thymus and spleen, which are potential sites of T cell transformation. Taken together, our data provide the first evidence that γδ T cells play an important role in the pathogenesis and tumor formation of this highly oncogenic herpesvirus.

IMPORTANCE

Gamma delta (γδ) T cells are the most abundant T cells in chickens, but their role in fighting pathogens remains poorly understood. Marek’s disease virus (MDV) is an important veterinary pathogen, that causes one of the most frequent cancers in animals and is used as a model for virus-induced tumor formation. Our study revealed that γδ T cells play a crucial role in combating MDV, as disease and tumor incidence drastically increased in the absence of these cells. γδ T cells restricted virus replication in the key lymphoid organs, thereby decreasing the likelihood of causing tumors and disease. This study provides novel insights into the role of γδ T cells in the pathogenesis of this highly oncogenic virus.
An efficient
in vivo
-inducible CRISPR interference system for group A
Streptococcus
genetic analysis and pathogenesis studies
Authors: Bjånes Elisabet , Stream Alexandra , Janssen Axel B. , Gibson Paddy S. , Bravo Afonso M. , Dahesh Samira , Baker Jonathon L. , Varble Andrew , Nizet Victor , Veening Jan-Willem
Published: July 2024

While genome-wide transposon mutagenesis screens have identified numerous essential genes in the significant human pathogen
Streptococcus pyogenes
(group A
Streptococcus
or GAS), many of their functions remain elusive. This knowledge gap is attributed in part to the limited molecular toolbox for controlling GAS gene expression and the bacterium’s poor genetic transformability. CRISPR interference (CRISPRi), using catalytically inactive GAS Cas9 (dCas9), is a powerful approach to specifically repress gene expression in both bacteria and eukaryotes, but ironically, it has never been harnessed for controlled gene expression in GAS. In this study, we present a highly transformable and fully virulent serotype M1T1 GAS strain and introduce a doxycycline-inducible CRISPRi system for efficient repression of bacterial gene expression. We demonstrate highly efficient, oligo-based single guide RNA cloning directly to GAS, enabling the construction of a gene knockdown strain in just 2 days, in contrast to the several weeks typically required. The system is shown to be titratable and functional both
in vitro
and
in vivo
using a murine model of GAS infection. Furthermore, we provide direct
in vivo
evidence that the expression of the conserved cell division gene
ftsZ
is essential for GAS virulence, highlighting its promise as a target for emerging FtsZ inhibitors. Finally, we introduce SpyBrowse (
https://veeninglab.com/SpyBrowse
), a comprehensive and user-friendly online resource for visually inspecting and exploring GAS genetic features. The tools and methodologies described in this work are poised to facilitate fundamental research in GAS, contribute to vaccine development, and aid in the discovery of antibiotic targets.

IMPORTANCE

While group A
Streptococcus
(GAS) remains a predominant cause of bacterial infections worldwide, there are limited genetic tools available to study its basic cell biology. Here, we bridge this gap by creating a highly transformable, fully virulent M1T1 GAS strain. In addition, we established a tight and titratable doxycycline-inducible system and developed CRISPR interference (CRISPRi) for controlled gene expression in GAS. We show that CRISPRi is functional
in vivo
in a mouse infection model. Additionally, we present SpyBrowse, an intuitive and accessible genome browser (
https://veeninglab.com/SpyBrowse
). Overall, this work overcomes significant technical challenges of working with GAS and, together with SpyBrowse, represents a valuable resource for researchers in the GAS field.
Cytomegalovirus-induced peroxynitrite promotes virus entry and contributes to pathogenesis in a murine model of infection
Authors: Amratia Pragati S. , Kerr-Jones Lauren E. , Chapman Lucy , Marsden Morgan , Clement Mathew , Stanton Richard J. , Humphreys Ian R.
Published: July 2024

There are no licensed vaccines for human cytomegalovirus (HCMV), and current antiviral drugs that target viral proteins are toxic and prone to resistance. Targeting host pathways essential for virus replication provides an alternate strategy that may reduce opportunities for drug resistance to occur. Oxidative stress is triggered by numerous viruses including HCMV. Peroxynitrite is a reactive nitrogen species that is formed during oxidative stress. Herein, we identified that HCMV rapidly induces the generation of intracellular peroxynitrite upon infection in a manner partially dependent upon xanthine oxidase generation. Peroxynitrite promoted HCMV infection in both cell-free and cell-associated infection systems in multiple cell types. Inhibiting peroxynitrite within the first 24 hours of infection prevented HCMV replication and peroxynitrite promoted cell entry and pp65 translocation into the host cell nuclei. Furthermore, using the murine cytomegalovirus model, we demonstrated that antagonizing peroxynitrite significantly reduces cytomegalovirus replication and pathogenesis
in vivo
. Overall, our study highlights a proviral role for peroxynitrite in CMV infection and implies that RNS and/or the mechanisms that induce their production could be targeted as a novel strategy to inhibit HCMV infection.

IMPORTANCE

Human cytomegalovirus (HCMV) causes significant disease in individuals with impaired or immature immune systems, such as transplant patients and after congenital infection. Antiviral drugs that target the virus directly are toxic and are susceptible to antiviral drug resistance due to virus mutations. An alternate strategy is to target processes within host cells that are required by the virus for replication. Herein, we show that HCMV infection triggers a highly reactive molecule, peroxynitrite, during the initial stages of infection. Peroxynitrite was required for the initial entry of the virus into the cell and promotes virus replication in multiple cell types, suggesting a broad pro-viral function. Importantly, targeting peroxynitrite dramatically inhibited cytomegalovirus replication in cells in the laboratory and in mice, suggesting that therapeutic targeting of this molecule and/or the cellular functions it regulates could represent a novel strategy to inhibit HCMV infection.
On the Nonlinear Two- and Three-Dimensional Klein–Gordon Equations Allowing Localized Solutions with Beatings of Coupled Oscillators
Authors: Salimov R. K. , Salimov T. R. , Ekomasov E. G.
Published: July 2024

Equations for two and three scalar fields, which allow localized solutions with beatings of coupled oscillators, have been presented. The amplitude of oscillations of a localized perturbation for one field decreases periodically gradually to a minimum and the amplitudes of the other scalar fields increase to a maximum; then, the reverse process occurs. In this case, all fields except for one are initially either in the state of a background solution with a small amplitude or equal to zero. Such solutions can be interesting due to analogy with neutrino oscillations. Equations of motion, where the perturbation of one of the components is obligatorily accompanied by the perturbation of the second and third components even in zeroth background state, have also been presented. It has been shown that these equations satisfy the energy conservation law.
Near fatal case of Lucio leprosy with Lucio phenomenon with pleomorphic features and its successful management from a non-endemic area
Authors: Daniel Samuel Jeyaraj , Rajan Manipriya , Ruba Merin Vasantha , Aravamuthan Ramesh
Published: July 2024

Lucio leprosy is a diffuse non-nodular form of lepromatous leprosy. Lucio phenomenon is a type of reactional state which occurs in untreated cases due to the bacillary invasion of endothelial cells. We hereby describe a histopathologically confirmed case of Lucio leprosy with Lucio phenomenon. The patient presented with pleomorphic clinical features and started taking antileprosy treatment and systemic steroids. After few days of admission, she developed deep ulcers exposing the fascia. She also developed cardiogenic shock secondary to septicaemia. She was managed with inotropes and broad-spectrum antibiotics. The patient was given appropriate wound care and the ulcers healed within a period of 3 months and antileprosy drugs were continued. Our patient is a de novo case of Lucio leprosy with Lucio phenomenon and pleomorphic clinical features who developed near fatal septic shock. She was managed successfully. Despite the extensive disease manifestation, all the wounds healed completely.
Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome
Authors: Sathiyaseelan Sri Lakshmi , Krishna Kavita , Agarwal Deepti , Oswal Jitendra Shankarlal
Published: July 2024

Camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) is a rare autosomal recessive disease caused by mutation in proteoglycan 4 (PRG4) gene on chromosome 1q25-q31. We faced a dilemma and delay in diagnosis in two sisters. The elder sister had pericardial effusion with constrictive pericarditis, underwent pericardiectomy and received empirical treatment for suspected tuberculosis. After 2 years, she developed bilateral knee swelling with restriction of movement. At the same time, her younger sister also presented with bilateral knee swelling which aroused the suspicion of genetic disease. The whole-genome sequencing revealed homozygous PRG4 mutation suggestive of CACP syndrome.
Ectopic pregnancy in uterosacral ligament following in vitro fertilisation (IVF) in a patient with Allen-Masters syndrome
Authors: Solomon Adam , Mastroliasa Salvatore , Andre Nicolas , Schwarzman Polina
Published: July 2024

We describe the case of a woman with mild endometriosis and Allen-Masters syndrome after in vitro fertilisation (IVF), presenting at 7 weeks 2 days gestation with abdominal pain. A transvaginal ultrasound revealed a gestational sac with a non-viable fetus near the right ovary. Laparoscopy was performed due to escalating abdominal pain which revealed a ruptured ectopic pregnancy at the right uterosacral ligament (USL) and blood in the pouch of Douglas. A peritoneal incision along the USL facilitated drainage and removal of the ectopic pregnancy. A pathological investigation described the presence of endometrial tissue directly adjacent to products of conception, which suggested a retroperitoneal implantation that may have been facilitated by the presence of an endometriotic lesion. This case underscores the distinctive clinical trajectory of unconventional ectopic pregnancies, provides novel insights into the pathophysiological mechanism of ectopic implantation and underscores the crucial role of comprehensive patient assessment during IVF and subsequent pregnancy in ensuring effective management.
Rare mandibular condition presenting as trismus: an exploration of IgG4-related disease
Authors: Chawla Jitendra , Rajagopal Poongodi , Yerragudi Navaneeth , Anuvindha JS
Published: July 2024

A woman in her 30s presented with a 12-month history of reduced mouth opening and swelling on the right side of her mandible. The swelling was non-tender and firm on palpation. The swelling began to increase in size after the extraction of her carious wisdom tooth. Histopathological and serological examinations confirmed the diagnosis of IgG4-related disease, manifested as a mass in the mandible. The patient was prescribed oral corticosteroids at a tapering dosage over 8 weeks. After 3 months, there was an improvement in the patient’s mouth opening and a reduction in the size of the swelling. The patient remains in follow-up care. Including IgG4-related disease in the list of potential diagnoses for oral soft tissue masses is crucial, given their positive response to medical treatment, highlighting the significance of an accurate diagnosis to prevent unnecessary surgery, with oral lesions potentially serving as early indicators before multiorgan complications arise.
Second-generation checkpoint inhibitors and Treg depletion synergize with a mouse cancer vaccine in accordance with tumor microenvironment characterization
Authors: Becker William , Olkhanud Purevdorj B , Seishima Noriko , Moreno Paloma A , Goldfarbmuren Katherine C , Maeng Hoyoung M , Berzofsky Jay A
Published: July 2024

Background

Despite advances in checkpoint inhibitor (CPI) therapy for cancer treatment, many cancers remain resistant. Tumors deemed “cold” based on lack of T cell infiltration show reduced potential for CPI therapy. Cancer vaccines may overcome the inadequacy of existing T cells by inducing the needed antitumor T cell response to synergize with CPIs and overcome resistance.

Methods

CT26 and TC1 tumor cells were injected subcutaneously into mice. Mice were treated with combinations of CPIs alone or a cancer vaccine specific to the tumor antigen E7 present in TC1 cells. CPIs for the TC1 model were selected because of immunophenotyping TC1 tumors. Antitumor and protumor immunity, tumor size and survival, sequence and timing of vaccine and CPI administration, and efficacy of treatment in young and aged mice were probed.

Results

While “hot” CT26 tumors are treatable with combinations of second-generation CPIs alone or with anti-TGFβ, “cold” TC1 tumor reduction requires the synergy of a tumor-antigen-specific vaccine in combination with two CPIs, anti-TIGIT and anti-PD-L1, predicted by tumor microenvironment (TME) characterization. The synergistic triple combination delays tumor growth better than any pairwise combination and improves survival in a CD8+T cell-dependent manner. Depletion of CD4+T cells improved the treatment response, and depleting regulatory T cells (Treg) revealed Tregs to be inhibiting the response as also predicted from TME analysis. We found the sequence of CPI and vaccine administration dictates the success of the treatment, and the triple combination administered concurrently induces the highest E7-specific T cell response. Contrary to young mice, in aged mice, the cancer vaccine alone is ineffective, requiring the CPIs to delay tumor growth.

Conclusions

These findings show how pre-existing or vaccine-mediated de novo T cell responses can both be amplified by and facilitate synergistic CPIs and Treg depletion that together lead to greater survival, and how analysis of the TME can help rationally design combination therapies and precision medicine to enhance clinical response to CPI and cancer vaccine therapy.
A methodological approach to rock art survey and recording via drone. The application to the Rock Art of the Mediterranean Basin of the Iberian Peninsula assemblage
Authors: Hernández Francisco Javier Molina , González Virginia Barciela , López Juan F. Ruiz , Briz Ximo Martorell
Published: July 2024

The significant advancement in drone technology has led to increased usage across different scientific domains. In the field of archaeology, drones became increasingly popular a decade ago, primarily for photogrammetric documentation or aerial photography. Since then, researchers have experimented with new applications, notably utilizing LiDAR imagery to enhance archaeological surveying. In this context, one of the latest applications involves surveying open-air rock art shelters in inaccessible locations to search for prehistoric rock art imagery. The current study involves refining the methodology used for this purpose in the territory of UNESCO’s World Heritage List property Rock Art of the Mediterranean Basin of the Iberian Peninsula, utilizing a DJI Mavic 3 drone, which represents a significant improvement over previous models. On the other hand, it highlights the potential for its utilization in conservation studies and managing human activity in their environments, considering the threats to which these sites are currently exposed.
Citizen science for social physics: digital tools and participation
Authors: Perelló Josep , Larroya Ferran , Bonhoure Isabelle , Peter Franziska
Published: July 2024

Social physics is an active and diverse field in which many scientists with formal training in physics study a broad class of complex social phenomena. Social physics investigates societal problems but most often does not count on the active and conscious participation of the citizens. We here want to support the idea that citizen science, and more particularly citizen social science, can contribute to the broad field of social physics. The current manuscript is not a review paper of citizen science projects from the context of social physics as there are still too few experiences in this context. We, in contrast, present a selection of our own experiences during the last decade to extract key learnings and further reflect on citizen science practices for social physics. We first describe several human mobility experiments in urban contexts with the participation of concerned young students, old women, or other different groups of neighbors. We second share how we have studied community mental healthcare provision in collaboration with a civil society organization and with the intense involvement of persons with lived experience in mental health. In both cases, we narrow down the discussion to digital tools being used and the involved participatory dynamics. In this way, we share key learnings to enhance a synergistic relationship between social physics and citizen science and with the aim of increasing the societal impact of the research on complex social phenomena.
Numerical intercomparison of PHITS and Geant4 Monte Carlo codes for fast neutron inelastic scattering applications
Authors: Meleshenkovskii I. , Van den Brandt K. , Ogawa T. , Datema C. , Mauerhofer E.
Published: July 2024

Fast neutron inelastic scattering is a promising non-destructive assay technique for various analytical applications. As an active neutron interrogation technique, its performance is a function of various different factors and parameters that require optimization. Monte Carlo simulation codes are indispensable for such tasks. However, the internal simulation routines implemented in such codes can rely on different physical models that can yield discrepancies in the simulation results. In this work we conduct an intercomparison of PHITS and Geant4 codes performance in application to fast neutron inelastic scattering simulations. The goal of this paper is twofold. First, we explain the differences in code configuration with respect to gamma and neutron transport, as well as internal simulation routines. Second, we conduct a performance assessment of the two codes using two different measurement configurations. One configuration consisted of a source of gamma rays in a broad energy range (100–9000 keV) and a CeBr3 detector. The other configuration consisted of a monoenergetic 2.5 MeV fast neutron source, Fe, Nd, Dy, B targets and a CeBr3 detector. Selected simulation configurations were chosen with a goal to compare the performance differences in neutron energy distribution, produced prompt gamma rays and energy deposition in CeBr3 detector between the two codes. Results of our study reveal a good coherence of both codes performance in the application of fast neutron inelastic scattering simulations. The simulation geometries and observed differences are described in detail.
A Computation of the Ninth Dedekind Number Using FPGA Supercomputing
Authors: Van Hirtum Lennart , De Causmaecker Patrick , Goemaere Jens , Kenter Tobias , Riebler Heinrich , Lass Michael , Plessl Christian
Published: July 2024

This manuscript makes the claim of having computed the

\(9\)

th Dedekind number, D(9). This was done by accelerating the core operation of the process with an efficient FPGA design that outperforms an optimized 64-core CPU reference by 95

\(\times\)

. The FPGA execution was parallelized on the Noctua 2 supercomputer at Paderborn University. The resulting value for D(9) is 286386577668298411128469151667598498812366. This value can be verified in two steps. We have made the data file containing the 490 M results available, each of which can be verified separately on CPU, and the whole file sums to our proposed value. The paper explains the mathematical approach in the first part, before putting the focus on a deep dive into the FPGA accelerator implementation followed by a performance analysis. The FPGA implementation was done in Register-Transfer Level using a dual-clock architecture and shows how we achieved an impressive FMax of 450 MHz on the targeted Stratix 10 GX 2,800 FPGAs. The total compute time used was 47,000 FPGA hours.
Multielectron Dynamics in the Condensed Phase: Quantum Structure-Function Relationships
Authors: Eaves Joel D.
Published: July 2024

Quantum information promises dramatic advances in computing last seen in the digital revolution, but quantum hardware is fragile, noisy, and resource intensive. Chemistry has a role in developing new materials for quantum information that are robust to noise, scalable, and operable in ambient conditions. While molecular structure is the foundation for understanding mechanism and reactivity, molecular structure/quantum function relationships remain mostly undiscovered. Using singlet fission as a specific example of a multielectron process capable of producing long-lived spin-entangled electronic states at high temperatures, I describe how to exploit molecular structure and symmetry to gain quantum function and how some principles learned from singlet fission apply more broadly to quantum science.
Micrometer Scale X-ray CT-Informed Optimization of Heterogeneous Pore Distribution in Double Layered Thick LiNCM 811 Cathode
Authors: Pan Bonian , Lee Young-Geun , Wu Xinsheng , Whitacre Jay
Published: July 2024

The pore structure of lithium-ion battery electrodes heavily influences ion transport and thus their deliverable capacity, especially at higher rates. Ideally, a gradient pore distribution favoring higher porosity near the separator side can enable faster ion transport at higher cycling rates. We present here a two-layer heterogenous cathode design using traditional NCM 811 material featuring a three-dimensional design space of this cathode design. An efficient characterization technique that combines fast micrometer-scale X-ray computed tomography and pore network modeling was developed, providing critical information regarding the ion transport pathways inside the cathode. Based on the X-ray CT data and performance characteristics obtained, we created a comprehensive profile of cathode rate performance as a function of their pore distribution with easily identifiable advantaged configurations for different cycling scenarios.
Electrochemical H2O2 Production Modelling for an Electrochemical Bandage
Authors: Ozdemir Dilara , Picioreanu Cristian , Patel Robin , Beyenal Haluk
Published: July 2024

Hydrogen peroxide (H2O2) is an environmentally friendly oxidizing agent used to treat wound infections. We have developed an electrochemical bandage (e-bandage), which generates H2O2 in situ and shown that it exhibites in vitro and in vivo efficacy. The electrochemical bandage comprises carbon fabric working and counter electrodes, as well as an Ag/AgCl quasi-reference electrode, separated by cotton fabric and the electrolyte is delivered by Xanthan gum with phosphate buffer saline. While the chemistry and electrochemistry of the e-bandage have been experimentally characterized, the system level description could aid in better designing these devices. Here, a model called electrochemical hydrogen peroxide production (EHPP) was used to evaluate factors influencing electrochemical generation of H2O2, including electrode potential, diffusion and reaction rates, temperature, and various geometries. EHPP model parameters estimated based on experimental results indicate that: (i) with diffusion limitations caused by changes in physical conditions (e.g., drying of hydrogel), the rate of H2O2 generation decreases, (ii) higher working electrode overpotentials increase H2O2 generation and higher counter electrode overpotentials do not affect H2O2 generation, (iii) increasing the distance between electrodes by adding more hydrogel reduces H2O2 generation, (iv) net H2O2 generation decreases ∼12% with temperature, and (v) H2O2 production is most effective in the initial 48 h of operation.
Correlation of syndecan gene amplification with metastatic potential and clinical outcomes in carcinomas
Authors: Kim Sewoon , Yang Hyeonju , Cho Subin , Jang Yunjung , Han Inn-Oc , Oh Eok-Soo
Published: July 2024

Cell surface receptors play crucial roles in cellular responses to extracellular ligands, helping to modulate the functions of a cell based on information coming from outside the cell. Syndecan refers to a family of cell adhesion receptors that regulate both extracellular and cytosolic events. Alteration of syndecan expression disrupts regulatory mechanisms in a cell type-specific fashion, often leading to serious diseases, notably cancer. Given the multifaceted functions and distinct tissue distributions of syndecan, it will be important to unravel the gene-level intricacies of syndecan expression and thereby further understand its involvement in various carcinogenic processes. Although accumulating evidence indicates that the protein expression patterns of syndecan family members are significantly altered in cancer cells, the underlying gene-level mechanisms remain largely unknown. This review endeavors to explore syndecan gene expression levels across different cancer types by scrutinizing extensive cancer genome datasets using tools such as cBioPortal. Our analysis unveils that somatic mutations in SDC genes are rare occurrences, whereas copy number alterations are frequently observed across diverse cancers, particularly in SDC2 and SDC4. Notably, amplifications of SDC2 and SDC4 correlate with heightened metastatic potential and dismal prognosis. This underscores the recurrent nature of SDC2 and SDC4 amplifications during carcinogenesis and sheds light on their role in promoting cancer activity through augmented protein expression. The identification of these amplifications not only enriches our understanding of carcinogenic mechanisms but also hints at the potential therapeutic avenue of targeting SDC2 and SDC4 to curb cancer cell proliferation and metastasis.
A Bi‐Objective Stochastic Model of Locating‐Allocating‐Routing Relief and Rescue in Disaster Response Conditions: An Accelerated Benders Decomposition
Authors: Baygan Behrooz , Mehrabian Ahmad , Yousefi Nejad Attari Mahdi , Doostideilami Mohammad Jafar
Published: July 2024

Problem Statement. Proper and timely relief in the postdisaster phase is very important to minimize victims and casualties. It is necessary to assess the needs of the affected points and provide relief in the shortest possible time without wasting time. For this purpose, it is necessary and vital to determine the location of care centers, temporary accommodation centers, and routing to distribution vital and medical items. The Proposed Approach. In this paper, using a scenario‐based stochastic planning mathematical model, postdisaster relief is discussed. Also, attention has been paid to the distribution of vital items by using routing. Contributions. By using the epsilon constraint method, a strong efficient solution has been achieved for model’s objectives, and also a sensitivity analysis has been performed on some of the model’s parameters. Also, an accelerated stochastic benders decomposition algorithm is suggested to solve the problem modeled in this paper. To speed up the convergence of the solution algorithm, valid inequalities are introduced to get better quality lower bounds. Results. The results of the research show that the simultaneous consideration of the relief evacuation and distribution process improves the relief logistics process.
Table S2 from Single-Cell and Spatial Transcriptome Profiling Identifies the Transcription Factor BHLHE40 as a Driver of EMT in Metastatic Colorectal Cancer
Authors: Yang Sheng , Zhang Dongsheng , Sun Qingyang , Nie Hongxu , Zhang Yue , Wang Xiaowei , Huang Yuanjian , Sun Yueming
Published: July 2024

Supplementary Table S2: Relevant clinical information of 80 colorectal cancer patients in IHC was displayed.
Figure S6 from Single-Cell and Spatial Transcriptome Profiling Identifies the Transcription Factor BHLHE40 as a Driver of EMT in Metastatic Colorectal Cancer
Authors: Yang Sheng , Zhang Dongsheng , Sun Qingyang , Nie Hongxu , Zhang Yue , Wang Xiaowei , Huang Yuanjian , Sun Yueming
Published: July 2024

Figure S6. Survival analysis of the protein expression of BHLHE40 in the TMA. (A, B) The KM plots showing the OS and DFS of the BHLHE40 high and the BHLHE40 low groups in the TMA of 80 colorectal cancer patient samples.
Supplementary Figure 7 from GPR1 and CMKLR1 Control Lipid Metabolism to Support the Development of Clear Cell Renal Cell Carcinoma
Authors: Wang Dazhi , Mahmud Iqbal , Thakur Vijay S. , Tan Sze Kiat , Isom Daniel G. , Lombard David B. , Gonzalgo Mark L. , Kryvenko Oleksandr N. , Lorenzi Philip L. , Tcheuyap Vanina T. , Brugarolas James , Welford Scott M.
Published: July 2024

Supplementary Figure 7
Supplementary Figure 10 from GPR1 and CMKLR1 Control Lipid Metabolism to Support the Development of Clear Cell Renal Cell Carcinoma
Authors: Wang Dazhi , Mahmud Iqbal , Thakur Vijay S. , Tan Sze Kiat , Isom Daniel G. , Lombard David B. , Gonzalgo Mark L. , Kryvenko Oleksandr N. , Lorenzi Philip L. , Tcheuyap Vanina T. , Brugarolas James , Welford Scott M.
Published: July 2024

Supplementary Figure 10
Supplementary Fig S7 from A Tetravalent Bispecific Antibody Selectively Inhibits Diverse FGFR3 Oncogenic Variants
Authors: Yang Yan , Suhasini Avvaru N. , Jiang Zaoli , Liu Nina , Rosconi Michael , Zhang Bojie , Li Yinyin , Dudgeon Drew , Seong Changhyun , Kim Steven , Rafique Ashique , Huang Tammy , Bhosle Sangram , Krueger Pamela , Ullman Erica , Olson William , Lin John C. , Shen Yang , Daly Christopher
Published: July 2024

Supplementary Fig S7
Supplementary Tables 1–3 from Omental Preadipocytes Stimulate Matrix Remodeling and IGF Signaling to Support Ovarian Cancer Metastasis
Authors: Waters Jennifer A. , Robinson Mikella , Lujano-Olazaba Omar , Lucht Cassidy , Gilbert Samuel F. , House Carrie D.
Published: July 2024

Antibody information, Taqman probe information, and Gene expression data