bluuebunny/crossref_metadata_2025 huggingface dataset:
Post kala-azar dermal leishmaniasis in the Indian sub-continent: challenges and strategies for elimination
Authors: Kumar Awnish , Singh Vishal Kumar , Tiwari Rahul , Madhukar Prasoon , Rajneesh  , Kumar Shashi , Gautam Vibhav , Engwerda Christian , Sundar Shyam , Kumar Rajiv
Published: August 2023

Visceral leishmaniasis (VL) is a severe and often fatal form of leishmaniasis caused by Leishmania donovani in the Indian sub-continent. Post Kala-azar Dermal Leishmaniasis (PKDL) is a late cutaneous manifestation of VL, typically occurring after apparent cure of VL, but sometimes even without a prior history of VL in India. PKDL serves as a significant yet neglected reservoir of infection and plays a crucial role in the transmission of the disease, posing a serious threat to the VL elimination program in the Indian sub-continent. Therefore, the eradication of PKDL should be a priority within the current VL elimination program aimed at achieving a goal of less than 1 case per 10,000 in the population at the district or sub-district levels of VL endemic areas. To accomplish this, a comprehensive understanding of the pathogenesis of PKDL is essential, as well as developing strategies for disease management. This review provides an overview of the current status of diagnosis and treatment options for PKDL, highlighting our current knowledge of the immune responses underlying disease development and progression. Additionally, the review discusses the impact of PKDL on elimination programs and propose strategies to overcome this challenge and achieve the goal of elimination. By addressing the diagnostic and therapeutic gaps, optimizing surveillance and control measures, and implementing effective intervention strategies, it is possible to mitigate the burden of PKDL and facilitate the successful elimination of VL in the Indian sub-continent.
Roles of differently polarized macrophages in the initiation and progressionof pancreatic cancer
Authors: Storz Peter
Published: August 2023

During development of pancreatic cancer macrophage-mediated inflammatory processes and the formation of cancerous lesions are tightly connected. Based on insight from mouse models we provide an overview on the functions of classically-activated pro-inflammatory and alternatively-activated anti-inflammatory macrophages in the initiation and progression of pancreatic cancer. We highlight their roles in earliest events of tumor initiation such as acinar-to-ductal metaplasia (ADM), organization of the fibrotic lesion microenvironment, and growth of low-grade (LG) lesions. We then discuss their roles as tumor-associated macrophages (TAM) in progression to high-grade (HG) lesions with a cancerous invasive phenotype and an immunosuppressive microenvironment. Another focus is on how targeting these macrophage populations can affect immunosuppression, fibrosis and responses to chemotherapy, and eventually how this knowledge could be used for novel therapy approaches for patients with pancreatic ductal adenocarcinoma (PDA).
Double-negative-2 B cells are the major synovial plasma cell precursor in rheumatoid arthritis
Authors: Wing Elinor , Sutherland Catherine , Miles Katherine , Gray David , Goodyear Carl S. , Otto Thomas D. , Breusch Stefan , Cowan Graeme , Gray Mohini
Published: August 2023

B cells are key pathogenic drivers of chronic inflammation in rheumatoid arthritis (RA). There is limited understanding of the relationship between synovial B cell subsets and pathogenic antibody secreting cells (ASCs). This knowledge is crucial for the development of more targeted B-cell depleting therapies. While CD11c+ double-negative 2 (DN2) B cells have been suggested as an ASC precursor in lupus, to date there is no proven link between the two subsets in RA. We have used both single-cell gene expression and BCR sequencing to study synovial B cells from patients with established RA, in addition to flow cytometry of circulating B cells. To better understand the differentiation patterns within the diseased tissue, a combination of RNA-based trajectory inference and clonal lineage analysis of BCR relationships were used. Both forms of analysis indicated that DN2 B cells serve as a major precursors to synovial ASCs. This study advances our understanding of B cells in RA and reveals the origin of pathogenic ASCs in the RA synovium. Given the significant role of DN2 B cells as a progenitor to pathogenic B cells in RA, it is important to conduct additional research to investigate the origins of DN2 B cells in RA and explore their potential as therapeutic targets in place of the less specific pan-B cells depletion therapies currently in use.
Fresh submarine groundwater discharge offshore Wellington (New Zealand): hydroacoustic characteristics and its influence on seafloor geomorphology
Authors: Hoffmann Jasper J. L. , Mountjoy Joshu J. , Spain Erica , Gall Mark , Tait Leigh W. , Ladroit Yoann , Micallef Aaron
Published: August 2023

Fresh submarine groundwater discharge (FSGD) influences the biogeochemistry of coastal areas and can be a proxy for potential untapped resources of offshore freshened groundwater (OFG). In most areas however, the onshore-offshore connection and the recharge characteristics of offshore aquifers are poorly constrained, making a potential exploitation of this resource challenging. Offshore Wellington (New Zealand), a well-defined onshore aquifer system extends beneath the harbour, where substantial amounts of freshwater seep out from the ocean floor. The aquifer system has been studied in detail and recently the first attempts worldwide have been made here to use the offshore groundwater as a future source of drinking water. However, the locations and extent of FSGD as well as its influence on seafloor morphology are still poorly understood. Exact localisation of FSGD sites is essential to sample and quantify discharging waters but remains challenging due to a lack of robust and appropriate measurement procedures. Novel sensing strategies, such as the influence of seeping groundwater on hydroacoustic water column reflectivity could greatly improve the identification of groundwater discharge locations worldwide. Therefore, we use a multidisciplinary dataset and evaluate different methodologies to map the spatial extent of FSGD sites and determine their geomorphologic expressions on the seafloor of Wellington Harbour. In this study, single and multibeam hydroacoustics and towfish (temperature, salinity and turbidity) transects were combined with remotely operated vehicle (ROV) dives and sediment cores to better characterise FSGD sites. We observed several hundred seafloor depressions (pockmarks) that we attribute to continuous seepage of gas and groundwater from the seafloor. Different pockmark morphologies indicate different fluid flow regimes and the persistent flow allows even small pockmarks to remain unchanged over time, while the geomorphologic expressions of anchor scours on the seafloor diminish in the same region. Enhanced hydroacoustic reflections in the water column within and above the pockmarks indicate suspended sediment particles, which are likely kept in suspension by discharging groundwater and density boundaries.
Dynamics of oxygen sources and sinks in the Baltic Sea under different nutrient inputs
Authors: Naumov Lev , Meier H. E. Markus , Neumann Thomas
Published: August 2023

The Baltic Sea is one of the marine systems suffering from pronounced man-made hypoxia due to the elevated nutrient loads from land. To mitigate hypoxia expansion and to return the Baltic Sea to a good environmental state, the Baltic Sea Action Plan (BSAP), regulating the waterborne and airborne nutrient input, was adopted by all states surrounding the Baltic Sea. However, at the moment, no significant shrinking of the hypoxic area is observed. In this study, two scenario simulations of the future state of the deep parts of the central Baltic Sea (deeper than 70 meters) were carried out, utilizing a 3-dimensional numerical model. Climate change effects on meteorology, hydrology, and oceanic state were not included. We focused on O2 and H2S sources and sinks under different nutrient input scenarios. We found that under the BSAP scenario, all subbasins in the central Baltic Sea, especially the northern and western Gotland Basin, show significant improvement, namely, oxygenation and oxidation of the deposited reduced material, ceasing its advection to the upper layers and neighboring basins. We found that the nutrient loads are responsible for more than 60% and 80% of the O2 and H2S sources and sinks variability, respectively, at the interannual time scale. We showed that the Baltic Sea could return to the initial state in 1948, but under the more rigorous 0.5 BSAP scenario (nutrient input is halved compared to the BSAP). However, since we observed no hysteresis effect, the system would probably reach the initial state but over a timeframe longer than the 71-year future simulation period.
Sterile inflammation in liver transplantation
Authors: Kahan Riley , Cray Paul L. , Abraham Nader , Gao Qimeng , Hartwig Matthew G. , Pollara Justin J. , Barbas Andrew S.
Published: August 2023

Sterile inflammation is the immune response to damage-associated molecular patterns (DAMPs) released during cell death in the absence of foreign pathogens. In the setting of solid organ transplantation, ischemia-reperfusion injury results in mitochondria-mediated production of reactive oxygen and nitrogen species that are a major cause of uncontrolled cell death and release of various DAMPs from the graft tissue. When properly regulated, the immune response initiated by DAMP-sensing serves as means of damage control and is necessary for initiation of recovery pathways and re-establishment of homeostasis. In contrast, a dysregulated or overt sterile inflammatory response can inadvertently lead to further injury through recruitment of immune cells, innate immune cell activation, and sensitization of the adaptive immune system. In liver transplantation, sterile inflammation may manifest as early graft dysfunction, acute graft failure, or increased risk of immunosuppression-resistant rejection. Understanding the mechanisms of the development of sterile inflammation in the setting of liver transplantation is crucial for finding reliable biomarkers that predict graft function, and for development of therapeutic approaches to improve long-term transplant outcomes. Here, we discuss the recent advances that have been made to elucidate the early signs of sterile inflammation and extent of damage from it. We also discuss new therapeutics that may be effective in quelling the detrimental effects of sterile inflammation.
Mapping the microbial diversity associated with different geochemical regimes in the shallow-water hydrothermal vents of the Aeolian archipelago, Italy
Authors: Barosa Bernardo , Ferrillo Alessandra , Selci Matteo , Giardina Marco , Bastianoni Alessia , Correggia Monica , di Iorio Luciano , Bernardi Giulia , Cascone Martina , Capuozzo Rosaria , Intoccia Michele , Price Roy , Vetriani Costantino , Cordone Angelina , Giovannelli Donato
Published: August 2023

Shallow-water hydrothermal vents are unique marine environments ubiquitous along the coast of volcanically active regions of the planet. In contrast to their deep-sea counterparts, primary production at shallow-water vents relies on both photoautotrophy and chemoautotrophy. Such processes are supported by a range of geochemical regimes driven by different geological settings. The Aeolian archipelago, located in the southern Tyrrhenian sea, is characterized by intense hydrothermal activity and harbors some of the best sampled shallow-water vents of the Mediterranean Sea. Despite this, the correlation between microbial diversity, geochemical regimes and geological settings of the different volcanic islands of the archipelago is largely unknown. Here, we report the microbial diversity associated with six distinct shallow-water hydrothermal vents of the Aeolian Islands using a combination of 16S rRNA amplicon sequencing along with physicochemical and geochemical measurements. Samples were collected from biofilms, fluids and sediments from shallow vents on the islands of Lipari, Panarea, Salina, and Vulcano. Two new shallow vent locations are described here for the first time. Our results show the presence of diverse microbial communities consistent in their composition with the local geochemical regimes. The shallow water vents of the Aeolian Islands harbor highly diverse microbial community and should be included in future conservation efforts.
Further evidences of an emerging stingless bee-yeast symbiosis
Authors: de Paula Gabriela Toninato , Melo Weilan Gomes da Paixão , Castro Ivan de , Menezes Cristiano , Paludo Camila Raquel , Rosa Carlos Augusto , Pupo Mônica Tallarico
Published: August 2023

Symbiotic interactions between microorganisms and social insects have been described as crucial for the maintenance of these multitrophic systems, as observed for the stingless bee Scaptotrigona depilis and the yeast Zygosaccharomyces sp. SDBC30G1. The larvae of S. depilis ingest fungal filaments of Zygosaccharomyces sp. SDBC30G1 to obtain ergosterol, which is the precursor for the biosynthesis of ecdysteroids that modulate insect metamorphosis. In this work, we find a similar insect-microbe interaction in other species of stingless bees. We analyzed brood cell samples from 19 species of stingless bees collected in Brazil. The osmophilic yeast Zygosaccharomyces spp. was isolated from eight bee species, namely Scaptotrigona bipunctata, S. postica, S. tubiba, Tetragona clavipes, Melipona quadrifasciata, M. fasciculata, M. bicolor, and Partamona helleri. These yeasts form pseudohyphae and also accumulate ergosterol in lipid droplets, similar to the pattern observed for S. depilis. The phylogenetic analyses including various Zygosaccharomyces revealed that strains isolated from the brood cells formed a branch separated from the previously described Zygosaccharomyces species, suggesting that they are new species of this genus and reinforcing the symbiotic interaction with the host insects.
Klebsiella pneumoniae manipulates human macrophages to acquire iron
Authors: Grubwieser Philipp , Hilbe Richard , Gehrer Clemens Michael , Grander Manuel , Brigo Natascha , Hoffmann Alexander , Seifert Markus , Berger Sylvia , Theurl Igor , Nairz Manfred , Weiss Günter
Published: August 2023

Background

Klebsiella pneumoniae (KP) is a major cause of hospital-acquired infections, such as pneumonia. Moreover, it is classified as a pathogen of concern due to sprawling anti-microbial resistance. During infection, the gram-negative pathogen is capable of establishing an intracellular niche in macrophages by altering cellular metabolism. One factor critically affecting the host-pathogen interaction is the availability of essential nutrients, like iron, which is required for KP to proliferate but which also modulates anti-microbial immune effector pathways. We hypothesized, that KP manipulates macrophage iron homeostasis to acquire this crucial nutrient for sustained proliferation.

Methods

We applied an in-vitro infection model, in which human macrophage-like PMA-differentiated THP1 cells were infected with KP (strain ATCC 43816). During a 24-h course of infection, we quantified the number of intracellular bacteria via serial plating of cell lysates and evaluated the effects of different stimuli on intracellular bacterial numbers and iron acquisition. Furthermore, we analyzed host and pathogen specific gene and protein expression of key iron metabolism molecules.

Results

Viable bacteria are recovered from macrophage cell lysates during the course of infection, indicative of persistence of bacteria within host cells and inefficient pathogen clearing by macrophages. Strikingly, following KP infection macrophages strongly induce the expression of the main cellular iron importer transferrin-receptor-1 (TFR1). Accordingly, intracellular KP proliferation is further augmented by the addition of iron loaded transferrin. The induction of TFR1 is mediated via the STAT-6-IL-10 axis, and pharmacological inhibition of this pathway reduces macrophage iron uptake, elicits bacterial iron starvation, and decreases bacterial survival.

Conclusion

Our results suggest, that KP manipulates macrophage iron metabolism to acquire iron once confined inside the host cell and enforces intracellular bacterial persistence. This is facilitated by microbial mediated induction of TFR1 via the STAT-6-IL-10 axis. Mechanistic insights into immune metabolism will provide opportunities for the development of novel antimicrobial therapies.
Lipopolysaccharides from Ralstonia solanacearum induce a broad metabolomic response in Solanum lycopersicum
Authors: Zeiss Dylan R. , Molinaro Antonio , Steenkamp Paul A. , Silipo Alba , Piater Lizelle A. , Di Lorenzo Flaviana , Dubery Ian A.
Published: August 2023

Ralstonia solanacearum, one of the most destructive crop pathogens worldwide, causes bacterial wilt disease in a wide range of host plants. The major component of the outer membrane of Gram-negative bacteria, lipopolysaccharides (LPS), has been shown to function as elicitors of plant defense leading to the activation of signaling and defense pathways in several plant species. LPS from a R. solanacearum strain virulent on tomato (LPSR. sol.), were purified, chemically characterized, and structurally elucidated. The lipid A moiety consisted of tetra- to hexa-acylated bis-phosphorylated disaccharide backbone, also decorated by aminoarabinose residues in minor species, while the O-polysaccharide chain consisted of either linear tetrasaccharide or branched pentasaccharide repeating units containing α-L-rhamnose, N-acetyl-β-D-glucosamine, and β-L-xylose. These properties might be associated with the evasion of host surveillance, aiding the establishment of the infection. Using untargeted metabolomics, the effect of LPSR. sol. elicitation on the metabolome of Solanum lycopersicum leaves was investigated across three incubation time intervals with the application of UHPLC-MS for metabolic profiling. The results revealed the production of oxylipins, e.g., trihydroxy octadecenoic acid and trihydroxy octadecadienoic acid, as well as several hydroxycinnamic acid amide derivatives, e.g., coumaroyl tyramine and feruloyl tyramine, as phytochemicals that exhibit a positive correlation to LPSR. sol. treatment. Although the chemical properties of these metabolite classes have been studied, the functional roles of these compounds have not been fully elucidated. Overall, the results suggest that the features of the LPSR. sol. chemotype aid in limiting or attenuating the full deployment of small molecular host defenses and contribute to the understanding of the perturbation and reprogramming of host metabolism during biotic immune responses.
Glutamine metabolic reprogramming in hepatocellular carcinoma
Authors: Ye Yanyan , Yu Bodong , Wang Hua , Yi Fengming
Published: August 2023

Hepatocellular carcinoma (HCC) is a lethal disease with limited management strategies and poor prognosis. Metabolism alternations have been frequently unveiled in HCC, including glutamine metabolic reprogramming. The components of glutamine metabolism, such as glutamine synthetase, glutamate dehydrogenase, glutaminase, metabolites, and metabolite transporters, are validated to be potential biomarkers of HCC. Increased glutamine consumption is confirmed in HCC, which fuels proliferation by elevated glutamate dehydrogenase or upstream signals. Glutamine metabolism also serves as a nitrogen source for amino acid or nucleotide anabolism. In addition, more glutamine converts to glutathione as an antioxidant in HCC to protect HCC cells from oxidative stress. Moreover, glutamine metabolic reprogramming activates the mTORC signaling pathway to support tumor cell proliferation. Glutamine metabolism targeting therapy includes glutamine deprivation, related enzyme inhibitors, and transporters inhibitors. Together, glutamine metabolic reprogramming plays a pivotal role in HCC identification, proliferation, and progression.
Honokiol decreases alpha-synuclein mRNA levels and reveals novel targets for modulating alpha-synuclein expression
Authors: Fagen Sara J. , Burgess Jeremy D. , Lim Melina J. , Amerna Danilyn , Kaya Zeynep B. , Faroqi Ayman H. , Perisetla Priyanka , DeMeo Natasha N. , Stojkovska Iva , Quiriconi Drew J. , Mazzulli Joseph R. , Delenclos Marion , Boschen Suelen L. , McLean Pamela J.
Published: August 2023

Background

Intracytoplasmic inclusions comprised of aggregated alpha-synuclein (αsyn) represent a key histopathological feature of neurological disorders collectively termed “synucleinopathies,” which includes Parkinson’s disease (PD). Mutations and multiplications in the SNCA gene encoding αsyn cause familial forms of PD and a large body of evidence indicate a correlation between αsyn accumulation and disease. Decreasing αsyn expression is recognized as a valid target for PD therapeutics, with down-regulation of SNCA expression potentially attenuating downstream cascades of pathologic events. Here, we evaluated if Honokiol (HKL), a polyphenolic compound derived from magnolia tree bark with demonstrated neuroprotective properties, can modulate αsyn levels in multiple experimental models.

Methods

Human neuroglioma cells stably overexpressing αsyn, mouse primary neurons, and human iPSC-derived neurons were exposed to HKL and αsyn protein and SNCA messenger RNA levels were assessed. The effect of HKL on rotenone-induced overexpression of αsyn levels was further assessed and transcriptional profiling of mouse cortical neurons treated with HKL was performed to identify potential targets of HKL.

Results

We demonstrate that HKL can successfully reduce αsyn protein levels and SNCA expression in multiple in vitro models of PD with our data supporting a mechanism whereby HKL acts by post-transcriptional modulation of SNCA rather than modulating αsyn protein degradation. Transcriptional profiling of mouse cortical neurons treated with HKL identifies several differentially expressed genes (DEG) as potential targets to modulate SNCA expression.

Conclusion

This study supports a HKL-mediated downregulation of SNCA as a viable strategy to modify disease progression in PD and other synucleinopathies. HKL has potential as a powerful tool for investigating SNCA gene modulation and its downstream effects.
Defective hippocampal neurogenesis underlies cognitive impairment by carotid stenosis-induced cerebral hypoperfusion in mice
Authors: Fraga Enrique , Medina Violeta , Cuartero María Isabel , García-Culebras Alicia , Bravo-Ferrer Isabel , Hernández-Jiménez Macarena , Garcia-Segura Juan Manuel , Hurtado Olivia , Pradillo Jesus Miguel , Lizasoain Ignacio , Moro María Ángeles
Published: August 2023

Chronic cerebral hypoperfusion due to carotid artery stenosis is a major cause of vascular cognitive impairment and dementia (VCID). Bilateral carotid artery stenosis (BCAS) in rodents is a well-established model of VCID where most studies have focused on white matter pathology and subsequent cognitive deficit. Therefore, our aim was to study the implication of adult hippocampal neurogenesis in hypoperfusion-induced VCID in mice, and its relationship with cognitive hippocampal deficits. Mice were subjected to BCAS; 1 and 3 months later, hippocampal memory and neurogenesis/cell death were assessed, respectively, by the novel object location (NOL) and spontaneous alternation performance (SAP) tests and by immunohistology. Hypoperfusion was assessed by arterial spin labeling-magnetic resonance imaging (ASL-MRI). Hypoperfused mice displayed spatial memory deficits with decreased NOL recognition index. Along with the cognitive deficit, a reduced number of newborn neurons and their aberrant morphology indicated a remarkable impairment of the hippocampal neurogenesis. Both increased cell death in the subgranular zone (SGZ) and reduced neuroblast proliferation rate may account for newborn neurons number reduction. Our data demonstrate quantitative and qualitative impairment of adult hippocampal neurogenesis disturbances associated with cerebral hypoperfusion-cognitive deficits in mice. These findings pave the way for novel diagnostic and therapeutic targets for VCID.
Case report: 3D intracranial vessel wall MRI in Susac syndrome: potential relevance for diagnosis and therapeutic management
Authors: Lotti Antonio , Barilaro Alessandro , Mariottini Alice , Vannozzi Lorenzo , Piergentili Marco , Fainardi Enrico , Massacesi Luca
Published: August 2023

Background

Susac syndrome (SS) is a rare immune-mediated vasculitis affecting retina, inner ear and brain. Assessment of central nervous system (CNS) involvement is currently based on standard brain magnetic resonance imaging (MRI) sequences. Accuracy of three dimensional (3D)-vessel wall imaging (VWI) was compared to standard sequences and contrast-enhanced-3D T2-fluid attenuated inversion recovery (CE-FLAIR) to assess CNS disease activity in two cases of definite SS.

Methods

Brain MRI scan and retinal fluorescein angiogram (RFA) were performed at disease onset and at 1, 3, and 6 months after induction therapy start. CE-FLAIR and VWI based on 3D black-blood proton density weighted (PDW) with and without gadolinium were added to standard sequences on a 3 Tesla MRI scanner.

Results

Contrast enhanced-VWI (CE-VWI) detected an abnormal diffuse leptomeningeal enhancement (LME) in both cases at onset and during follow-up. Pathological enhancement on CE-VWI persisted at 6-month brain MRI, despite absence of new lesions and disappearance of LME on CE-FLAIR. Follow-up RFA revealed new arterial wall hyperfluorescence in both cases.

Conclusions

VWI may represent a useful tool for diagnosing and monitoring CNS disease activity in SS patients, as confirmed by concordance with RFA, leading treatment's choice and timing. Moreover, CE-VWI seemed at least as sensitive as CE-FLAIR in detecting LME, possibly being superior to the latter in posterior fossa. LME remission might be not accurate in predicting suppression of CNS inflammation in SS.
Pediatric hypnic headache: a systematic review
Authors: Ferretti Alessandro , Velardi Margherita , Fanfoni Claudia , Di Nardo Giovanni , Evangelisti Melania , Foiadelli Thomas , Orsini Alessandro , Del Pozzo Marco , Terrin Gianluca , Raucci Umberto , Striano Pasquale , Parisi Pasquale
Published: August 2023

Introduction

Hypnic headache (HH) is a primary headache, and it is considered a rare condition in children. The underlying mechanisms of HH are not yet fully understood. This systematic review aims to provide a comprehensive description of the clinical features of all published cases of pediatric HH. It will also discuss the differences in headache features between children and adults, the increased diagnostic sensitivity of the new diagnostic criteria (ICHD-3), potential pathophysiological hypotheses explaining the higher incidence in adults, differential diagnoses, and therapeutic options for children.

Methods

A systematic search was conducted to identify and analyze articles reporting cases of HH in patients under the age of 18. The search was performed in major medical databases including Cochrane Library, EBSCO, Embase, Medline, PubMed, Science Direct, Scopus, and Web of Science. The search covered the period from 1988 to April 2023. Relevant studies were screened for eligibility, and data extraction was performed using a standardized approach.

Results

Seven children with HH were included in the analysis. The mean age of onset for headache attacks was 10 ± 4.3 years (range 3–15 years). The average time from the start of headaches to diagnosis was 15.8 ± 25.0 months (range 1–60 months). Headache features in children differed from those observed in adult HH patients. Children experienced throbbing/pulsating pain, while adults reported dull/pressure-like pain. Children also had lower frequency and shorter duration of attacks compared to adults. The use of ICHD-3 criteria appeared to be more sensitive and inclusive for diagnosing HH in children compared to the previous ICHD-2 criteria. The association of headache attacks with sleep suggests that HH may be a primary disorder with a chronobiological origin. Hypothalamic dysfunction and melatonin dysregulation, which are more prevalent in older individuals, could potentially explain the higher incidence of HH in adults. Other primary headaches and secondary causes should be ruled out. Melatonin prophylactic therapy may be considered for pediatric patients.

Discussion

Further evaluation of the clinical features of HH in children is needed. The development of specific diagnostic criteria for pediatric cases could improve diagnostic rates and enhance the management of children with HH.
Decreased GABA levels of the anterior and posterior cingulate cortex are associated with executive dysfunction in mild cognitive impairment
Authors: Fu Xiaona , Qin Mengting , Liu Xiaoming , Cheng Lan , Zhang Lan , Zhang Xinli , Lei Yu , Zhou Qidong , Sun Peng , Lin Liangjie , Su Ying , Wang Jing
Published: August 2023

Background and purpose

Executive function impairment, a slight but noticeable cognitive deficit in mild cognitive impairment (MCI) patients, is influenced by gamma-aminobutyric acid (GABA) levels. Reduced cognitive function is accompanied by thinning of the cerebral cortex, which has higher GABA levels than white matter. However, the relationships among GABA levels, cortical thickness, and executive function in MCI patients have not yet been elucidated. We investigated the relationships among GABA levels, cortical thickness, and executive function in MCI patients.

Methods

In this study, a total of 36 MCI patients and 36 sex-, age-, and education-matched healthy controls (HC) were recruited. But 33 MCI patients and 35 HC were included because of head motion or poor data quality for three MCI patients and one HC. The levels of gamma-aminobutyric acid plus relative to creatine (GABA+/Cr) and glutamate-glutamine relative to creatine (Glx/Cr) in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) were measured using the Meshcher-Garwood point resolved spectroscopy (MEGA-PRESS) sequence. Metabolite ratios, cortical thickness, and executive function and their interrelationships were determined in the MCI and HC groups.

Results

Patients with MCI showed lower GABA+/Cr levels in the ACC and PCC. Combined levels of GABA+ and Glx in the ACC and GABA+ in the PCC showed good diagnostic efficacy for MCI (AUC: 0.82). But no differences in cortical thickness were found between the two groups. In the MCI group, lower GABA+/Cr level was correlated to worse performance on the digit span test backward, and the shape trail test-B. The cortical thickness was not associated with GABA+ levels and executive function in patients.

Conclusion

These results implied that decreased GABA levels in the ACC and PCC had a critical role in the early diagnosis of impaired executive function of MCI. Therefore, GABA in the ACC and PCC could be a potential diagnostic marker of the executive function decline of MCI.
SPIDEN: deep Spiking Neural Networks for efficient image denoising
Authors: Castagnetti Andrea , Pegatoquet Alain , Miramond Benoît
Published: August 2023

In recent years, Deep Convolutional Neural Networks (DCNNs) have outreached the performance of classical algorithms for image restoration tasks. However, most of these methods are not suited for computational efficiency. In this work, we investigate Spiking Neural Networks (SNNs) for the specific and uncovered case of image denoising, with the goal of reaching the performance of conventional DCNN while reducing the computational cost. This task is challenging for two reasons. First, as denoising is a regression task, the network has to predict a continuous value (i.e., the noise amplitude) for each pixel of the image, with high precision. Moreover, state of the art results have been obtained with deep networks that are notably difficult to train in the spiking domain. To overcome these issues, we propose a formal analysis of the information conversion processing carried out by the Integrate and Fire (IF) spiking neurons and we formalize the trade-off between conversion error and activation sparsity in SNNs. We then propose, for the first time, an image denoising solution based on SNNs. The SNN networks are trained directly in the spike domain using surrogate gradient learning and backpropagation through time. Experimental results show that the proposed SNN provides a level of performance close to the state of the art with CNN based solutions. Specifically, our SNN achieves 30.18 dB of signal-to-noise ratio on the Set12 dataset, which is only 0.25 dB below the performance of the equivalent DCNN. Moreover we show that this performance can be achieved with low latency, i.e., using few timesteps, and with a significant level of sparsity. Finally, we analyze the energy consumption for different network latencies and network sizes. We show that the energy consumption of SNNs increases with longer latencies, making them more energy efficient compared to CNNs only for very small inference latencies. However, we also show that by increasing the network size, SNNs can provide competitive denoising performance while reducing the energy consumption by 20%.
Unraveling the link: exploring the causal relationship between diabetes, multiple sclerosis, migraine, and Alzheimer’s disease through Mendelian randomization
Authors: Xue Hua , Zeng Li , Liu Shuangjuan
Published: August 2023

Introduction

Observational studies suggested that diabetes mellitus [type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM)], multiple sclerosis (MS), and migraine are associated with Alzheimer’s disease (AD). However, the causal link has not been fully elucidated. Thus, we aim to assess the causal link between T1DM, T2DM, MS, and migraine with the risk of AD using a two-sample Mendelian randomization (MR) study.

Methods

Genetic instruments were identified for AD, T1DM, T2DM, MS, and migraine respectively from genome-wide association study. MR analysis was conducted mainly using the inverse-variance weighted (IVW) method.

Results

The result of IVW method demonstrated that T2DM is causally associated with risk of AD (OR: 1.237, 95% CI: 1.099–1.391, P: 0.0003). According to the IVW method, there is no causal association between TIDM, MS, migraine, and the risk of AD (all p value > 0.05). Here we show, there is a causal link between T2DM and the risk of AD.

Conclusion

These findings highlight the significance of active monitoring and prevention of AD in T2DM patients. Further studies are required to actively search for the risk factors of T2DM combined with AD, explore the markers that can predict T2DM combined with AD, and intervene and treat early.
Remarkable impacts of probiotics supplementation in enhancing of the antioxidant status: results of an umbrella meta-analysis
Authors: Musazadeh Vali , Faghfouri Amir Hossein , Zarezadeh Meysam , Pakmehr Azin , Moghaddam Pooria Taghavi , Hamedi-Kalajahi Fateme , Jahandideh Arian , Ghoreishi Zohreh
Published: August 2023

Introduction

Numerous meta-analyses have demonstrated the beneficial effects of probiotics on oxidative stress biomarkers, although some studies have contradictory results. Therefore, the current research was conducted to obtain a precise and definite understanding on the impact of probiotics on oxidative stress biomarkers in adults.

Methods

We conducted a comprehensive systematic search of results on Scopus, PubMed, Embase, Web of Science, and Google Scholar dating up to March 2022. Fifteen meta-analyses were included in this umbrella meta-analysis. The random-effects model was employed to obtain the overall effect size. Subgroup analyses were carried out based on supplementation dosage and duration, mean age, and study population.

Results

Our results indicated that probiotics supplementation meaningfully decreased serum malondialdehyde (MDA) (ESWMD = −0.56, 95% CI: −0.72, −0.39; p < 0.001, and ESSMD = −0.50, 95% CI: −0.66, −0.34; p < 0.001). Moreover, the findings showed that probiotics resulted in a significant increase in total antioxidant capacity (TAC) (ESWMD = 29.18, 95% CI: 16.31, 42.04; p < 0.001, and ESSMD = 0.25, 95% CI: 0.02, 0.47; p = 0.032), total glutathione (GSH) (ESWMD: 30.65; 95% CI: 16.94, 44.35, p < 0.001), and nitric oxide (NO) (ESWMD: 1.48; 95% CI: 0.31, 2.65, p = 0.013; I2 = 51.7%, p = 0.043).

Discussion

Probiotics could be considered a strong agent in the reinforcement of antioxidant status and preventing the incidence of chronic diseases.
Sucrose-induced hyperglycemia dysregulates intestinal zinc metabolism and integrity: risk factors for chronic diseases
Authors: Mitchell Samuel Blake , Hung Yu-Han , Thorn Trista Lee , Zou Jiaqi , Baser Filiz , Gulec Sukru , Cheung Celeste , Aydemir Tolunay Beker
Published: August 2023

Objective

Zinc is an essential micronutrient that is critical for many physiological processes, including glucose metabolism, regulation of inflammation, and intestinal barrier function. Further, zinc dysregulation is associated with an increased risk of chronic inflammatory diseases such as type II diabetes, obesity, and inflammatory bowel disease. However, whether altered zinc status is a symptom or cause of disease onset remains unclear. Common symptoms of these three chronic diseases include the onset of increased intestinal permeability and zinc dyshomeostasis. The specific focus of this work is to investigate how dietary sources of intestinal permeability, such as high sucrose consumption, impact transporter-mediated zinc homeostasis and subsequent zinc-dependent physiology contributing to disease development.

Method

We used in vivo subchronic sucrose treatment, ex vivo intestinal organoid culture, and in vitro cell systems. We analyze the alterations in zinc metabolism and intestinal permeability and metabolic outcomes.

Results

We found that subchronic sucrose treatment resulted in systemic changes in steady-state zinc distribution and increased 65Zn transport (blood-to-intestine) along with greater ZIP14 expression at the basolateral membrane of the intestine. Further, sucrose treatment enhanced cell survival of intestinal epithelial cells, activation of the EGFR-AKT-STAT3 pathway, and intestinal permeability.

Conclusion

Our work suggests that subchronic high sucrose consumption alters systemic and intestinal zinc homeostasis linking diet-induced changes in zinc homeostasis to the intestinal permeability and onset of precursors for chronic disease.
The application of traditional machine learning and deep learning techniques in mammography: a review
Authors: Gao Ying’e , Lin Jingjing , Zhou Yuzhuo , Lin Rongjin
Published: August 2023

Breast cancer, the most prevalent malignant tumor among women, poses a significant threat to patients’ physical and mental well-being. Recent advances in early screening technology have facilitated the early detection of an increasing number of breast cancers, resulting in a substantial improvement in patients’ overall survival rates. The primary techniques used for early breast cancer diagnosis include mammography, breast ultrasound, breast MRI, and pathological examination. However, the clinical interpretation and analysis of the images produced by these technologies often involve significant labor costs and rely heavily on the expertise of clinicians, leading to inherent deviations. Consequently, artificial intelligence(AI) has emerged as a valuable technology in breast cancer diagnosis. Artificial intelligence includes Machine Learning(ML) and Deep Learning(DL). By simulating human behavior to learn from and process data, ML and DL aid in lesion localization reduce misdiagnosis rates, and improve accuracy. This narrative review provides a comprehensive review of the current research status of mammography using traditional ML and DL algorithms. It particularly highlights the latest advancements in DL methods for mammogram image analysis and offers insights into future development directions.
Bilateral orbital plasmacytomas as first sign of extramedullary progression post CAR-T therapy: case report and literature review
Authors: Nogués-Castell Javier , Feu-Basilio Silvia , Felguera García Óscar , Fernández de Larrea Carlos , Oliver-Caldés Aina , Balagué Ponz Olga , Fassi Jessica Matas
Published: August 2023

Background

Plasma cell leukemia (PCL) is an aggressive and rare form of plasma cell dyscrasia characterized by peripheral blood expression, poor prognosis, and high relapse rates. Extramedullary plasmacytomas are common in this entity and can affect various organs and soft tissues. Chimeric antigen receptor–T-cell (CAR-T) therapy is a novel immunotherapy for hematological malignancies with promising results. However, it is not indicated for PCL, and experience in this condition is limited. This case is a rare presentation of bilateral orbital plasmacytomas after CAR-T therapy in a patient with PCL history.

Case presentation

We present the case of a 51-year-old female patient with a history of previous primary PCL treated with CAR-T therapy achieving complete response and without evidence of systemic progression. Six months after the treatment, she developed subacute proptosis and ptosis on the left eye.

An orbital CT scan was performed and showed an orbital tumor in both eyes. A surgical biopsy with histological examination revealed plasma cells, consistent with a plasmacytoma. PET-CT and MRI confirmed the presence of tumors in both orbits. The patient was treated with dexamethasone and chemotherapy along with palliative radiation therapy to the left orbit which had a good response.

Conclusion

Orbital involvement in multiple myeloma and PCL is rare, with plasmacytomas being more common in other parts of the body. In this report, we present a case of a patient with PCL history, treated with multiple therapeutic lines including CAR-T therapy, who presented bilateral orbital plasmacytomas as the first sign of extramedullary progression after the treatment. This case should be considered by specialist to be aware that the orbits are a possible location of extramedullary progression.
An updated systemic review and meta-analysis on human papillomavirus in breast carcinogenesis
Authors: Awan Usman Ayub , Khattak Aamer Ali , Ahmed Noman , Guo Xingyi , Akhtar Sohail , Kamran Shehrish , Yongjing Zhao , Liu Jianbo , Khan Suliman
Published: August 2023

Background

Breast Cancer (BC) stands out as the widely prevalent malignancy among all the types of cancer affecting women worldwide. There is significant evidence that the pathogenicity of BC may be altered by Human Papillomavirus (HPV) infection; however, conclusive data are not yet available.

Methods

By searching five databases, including EMBASE, IBECS, PubMed, Scopus, Science Direct, Google Scholar, and Web of Science, a thorough systematic analysis was conducted on the prevalence of HPV in BC patients from 1990 to June 30, 2022. After applying extensive eligibility criteria, we selected 74 publications for further analysis based on the prevalence of HPV infections in breast tissues. All of the data were analyzed using a random-effects meta-analysis, Cochran Q test and I2 statistic were used to calculate the heterogeneity of the prevalence among these studies using subgroup analysis. Variations in the HPV prevalence estimates in different subgroups were evaluated by subgroup meta-analysis.

Results

In total, 3156 studies were initially screened, resulting in 93 full-text studies reviewed, with 74 meeting inclusion criteria. Among a total of 7156 BC biopsies, the pool prevalence of HPV was 25.6% (95% CI= 0.24-0.33, τ2 = 0.0369 with significant heterogeneity between estimates (I2 = 97% and p< 0.01). Consequently, 45 studies with available controls were further studied, and the prevalence of HPV in case-control studies was 26.2% with overall odds 5.55 (95% CI= 3.67-8.41, I2 = 38%, τ2 = 1.4878, p< 0.01). Further subgroup analysis of HPV revealed HPV-16 had a maximum prevalence of 9.6% (95% CI= 3.06-11.86, I2 = 0%, τ2 = 0.6111, p< 0.01). Among different geographical regions, Europe reported the maximum prevalence of HPV, i.e., 39.2% (95% CI=1.29-7.91, I2 = 18%, τ2 = 1.2911, p< 0.01). Overall distribution showed HPV-18 was a frequent HPV subtype reported in Australia.

Conclusion

Current study provides a global estimate of HPV prevalence in BC patients and demonstrates a significant association between this virus and BC etiology. Nevertheless, we recommend further investigation into the underlying mechanism is essential to validate this hypothesis.
The effectiveness of hyperbaric oxygen therapy for managing radiation-induced proctitis – results of a 10-year retrospective cohort study
Authors: Moreira Monteiro António , Alpuim Costa Diogo , Mareco Virgínia , Espiney Amaro Carla
Published: August 2023

Introduction

Despite modern radiotherapy (RT) techniques, radiation-induced proctitis (RIP) remains a significant complication of RT for pelvic organ malignancies. Over the last decades, an enormous therapeutic armamentarium has been considered in RIP, including hyperbaric oxygen therapy (HBOT). However, the evidence regarding the impact of HBOT on RIP is conflicting. This study aims to evaluate the effectiveness and safety of HBOT in the treatment of RIP.

Methods

Ten-year (2013-2023) retrospective analysis of all consecutive patients with RIP treated with HBOT at Centro de Medicina Subaquática e Hiperbárica (CMSH) (Armed Forces Hospital – Lisbon, Portugal). Patients were exposed to 100% oxygen at 2.5 ATA, in a multiplace first-class hyperbaric chamber, for 70-min periods, once daily, five times per week. Fisher’s exact test was performed using SPSS (version 23.0); p<0.05 was accepted as statistically significant.

Results

Of a total of 151 patients with RIP, 88 were included in the final analysis, of whom 38.6% evidenced other concurrent radiation-induced soft tissue lesions. The most reported primary pelvic tumor treated with RT was prostate cancer (77.3%), followed by cervical cancer (10.2%). Hematochezia was the most observed clinical manifestation (86.4%). After a median of 60 HBOT sessions (interquartile range [IQR]: 40-87.5), 62.5% and 31.8% of patients achieved a clinical complete and partial response, respectively, with a hematochezia resolution rate of 93.7% (complete or partial). While partial and complete responses require fewer than 70 sessions of HBOT in terms of overall RIP symptoms (p=0.069), isolated hematochezia tends to require at least 70 sessions (p=0.075). Individuals with at least two concurrent late radiation tissue injuries were associated with a complete response to HBOT (p=0.029). Only about 5.7% of patients did not respond to the treatment. Eighteen patients (20.5%) developed reversible ear barotrauma. The number of HBOT sessions was a predictor of HBOT side effects (odds ratio: 1.010; 95% confidence interval, 1.000-1.020; p=0.047).

Conclusion

The HBOT proved to be an effective and safe treatment for RIP refractory to medical and/or endoscopic treatments. This real-world evidence study adds value to published data on the management of RIP with HBOT.