bluuebunny/crossref_metadata_2025 huggingface dataset:
The Antiparasitic Potential of Senna alata Leaves Extracts and Fractions Against Marine Parasitic Leech Zeylanicobdella arugamensis
Authors: Jimmy Amanda Oya , Balu Alagar Venmathi Maran , Shapawi Rossita , Mazlan Nurzafirah , Shah Muhammad Dawood
Published: August 2024

Aquaculture has been a rapidly growing industry in Malaysia, contributing to the country's gross domestic product and enhancing food security and employment opportunities. Among the marine species cultivated in Malaysia are sea bass, snapper, and grouper. Unfortunately, the marine parasitic leech Zeylanicobdella arugamensis is posing a major threat to a wide variety of cultured marine fish species, including grouper. Various veterinary drugs are used to control parasitic leeches, which are toxic to fish and humans. So, the development of natural treatments from plants is vital. In response to this, Senna alata, also known as the Ringworm bush, was selected. This study aims to evaluate the antiparasitic activity of S. alata methanol extracts, its fractions and water extract against Z. arugamensis. The adult and mature leeches were divided into control and treatment groups. The methanol extract, its fractions (including hexane, chloroform, ethyl acetate, and butanol), and water extracts of S. alata were obtained. Various concentrations (100, 50, 25 and 12.5 mg/ml) of the extracts and fractions were prepared in 5% DMSO and concurrent notation of physico-chemical parameters. Upon exposure, the behaviour and mortality time of the parasitic leeches were recorded. The exposure to the extracts and fractions induced behavioural changes in the parasitic leeches, characterised by aggressive and abnormal swimming patterns coupled with an inability to attach their suction to the surface. Ultimately, complete mortality of parasitic leeches was obtained across extracts and fractions. Overall, the aqueous extract proved to be the most effective, as it displayed the shortest mortality time recorded among the extracts and fractions (2.38±0.15 to 33.08±3.52 minutes). Consequently, the study highlights the antiparasitic potential of the extracts and fractions of S. alata against parasitic leech Z. arugamensis infestation.
Cytotoxicity and Apoptotic DNA Fragmentation Evaluation of Ethanolic Extract of Phyllanthus niruri L. in Vero and Primary Feline Testicular Cells
Authors: Roslan Rasydan Hadi , Choong Siew Shean , Mohamed Maizan , Abu Bakar Md Zuki , Gilbert Brenda Sabrina , Noralidin Amalina , Izamin Izzati , Mohd Sani Nani Izreen , C. W. Zalati C. W. Salma , Badrul Hisham Nur Eizzati
Published: August 2024

Phyllanthus niruri or Dukung Anak is native to Southeast Asia, particularly in Malaysia and has been used as traditional preparations and as health supplements. However, previous studies have found that P. niruri can impair the male reproductive functions. With booming population of stray animals within the community, a new controlling method that is more affordable and safer must be developed. This study was aimed to explore the safety of P. niruri as a male herbal contraceptive to be used in veterinary medicine as one of the non-surgical sterilisation methods. For the preliminary part of this ongoing research, we have investigated the cytotoxicity activity of P. niruri ethanolic extract on Vero and primary feline testicular cells (FTC) and DNA apoptotic activity in FTC. Phyllanthus niruri extract was prepared using cold maceration method in 50% ethanol. The FTC were prepared from feline testes obtained from post-routine castration from local private veterinary clinics, while Vero cells were obtained from the archived cells of Virology Laboratory, Faculty of Veterinary Medicine Universiti Malaysia Kelantan (FPV UMK). The MTT assay was performed to evaluate the cytotoxicity of these plant extracts on FTC and Vero cells. Apoptosis was assessed using DNA laddering assay on extracted DNA of the treated FTC cells and observed the DNA patterns in gel electrophoresis. The 50% cytotoxic concentration (CC50) of the ethanolic extract of P. niruri was a dose dependent. The DNA laddering assay revealed that the plant extract does not induce apoptosis in FTC. Therefore, the study outcomes indicated that the ethanolic extract of P. niruri is potentially safe for animal use. However, in vivo studies are required to confirm these findings.
Aeroelastic Influence of Blade-Shaft Coupling in a 1 1/2-Stage Axial Compressor
Authors: Maroldt Niklas , Seume Joerg R.
Published: August 2024

The design process of turbomachinery is often constraint by aeroelastic phenomena. The design choices are limited by possible structural failure, which can be caused by high vibration amplitudes. In particular, damping has an important impact on these phenomena. In the absence of friction, damping is mainly created by aerodynamics. In this paper, additional damping created by the shaft will be investigated. This becomes relevant when blade vibrations with nodal diameters (ND) 1 and -1 couple structurally with shaft vibrations. To investigate the blade-shaft coupling, a simulation process is setup based on a full structural dynamic model of the blisk-shaft assembly and a harmonic balance computational fluid dynamics model to account for the aeroelastic effects. In addition, mistuning identification is performed based on an experimental modal analysis at standstill. All results are incorporated into a structural reduced order model that calculates the vibrational behavior of the blading. These results are compared to damping determined during operation using an acoustic excitation system and measured forced frequency responses. The numerical results agree well with the experimental results, i.e., within the measurement uncertainty. Furthermore, the blade-shaft coupling results in significant changes of the eigenfrequencies and damping. As a consequence, damping increases by up to twelve times due to the coupling. This reduces amplitudes by a factor of nine for the mistuned blade responses. Consequently, higher structural safety factors can be achieved by taking the blade-shaft coupling into account so that the remaining potentials in the aerodynamic design could be better exploited.
Relationship Between Wavy Liquid Film Dynamics and Droplet Formation From Trailing Edge
Authors: Kamada Yoshiaki , Murakami Keito , Wang Zhenying , Inoue Chihiro , Senoo Shigeki
Published: August 2024

Erosion of steam turbine blades due to coarse droplet impingement is a serious problem. The physical relationship is still elusive between the dynamics of wavy liquid film on a wall and the droplet dispersion from the trailing edge. In this study, we experimentally and theoretically investigate the liquid film subjected to the turbulent airflow and following fragmentation process under well-controlled flow conditions, where the airflow velocity is up to 100 m/s, and initial liquid film velocity is 0.06 and 0.10 m/s, and trailing edge thicknesses are 0.5, 1.0, and 2.0 mm. By applying the developed planar laser-induced fluorescence (PLIF)-based method with no use of artificial threshold of brightness, we quantify the film thickness and interfacial friction factor. As the airflow velocity increases, the liquid film instability promotes and the interfacial friction factor increases, much exceeding the Blasius correlation. When the liquid film reaches the trailing edge, several liquid columns extend by the Rayleigh–Taylor instability. We identify that the interfacial friction factor to accelerate the ligament corresponds to the Blasius correlation, distinct from the one on the wavy liquid film upstream. Incorporating the identified two interfacial friction factors, we successfully formulate the diameter of ligament as the characteristic lengthscale of the spreading droplet downstream. Derived formulation for the droplet statistics is well validated by the experimental results of mean and maximum diameters and size distribution.
Protecting the liver with PKD1
Authors: Wong Wei
Published: August 2024

Proliferation of somatic clones deficient in
PKD1
prevents fatty liver disease without resulting in tumors.
Acinetobacter baumannii
transformants expressing oxacillinases and metallo-β-lactamases that confer resistance to meropenem: new tools for anti-
Acinetobacter
drug development and AMR preparedness
Authors: Dubey Vineet , Farrington Nicola , Harper Nicholas , Johnson Adam , Horner Iona , Stevenson Adam , Parkes Annie , Hoare Lewis , Das Shampa , Hope William
Published: August 2024

Antimicrobial resistance (AMR) in
Acinetobacter baumannii
is an unmet medical need. Multiple drug-resistant/extremely drug-resistant strains of
A. baumannii
do not display growth well in
in vivo
models, and consequently, their response to antibacterial therapy is inconsistent. We addressed this issue by engineering carbapenem resistance motifs into the highly virulent genetic background of
A. baumannii
AB5075. This strain has a chromosomally encoded
oxa-23
that was deleted (
Δoxa-23
), then plasmids expressing
oxa-23
,
oxa-24/40
,
oxa-58
,
imp-1
,
vim-2
, and
ndm-1
were introduced to create the mutant strains. Each transformant was used as a challenge strain in a neutropenic murine thigh infection model and assessed for the extent of growth and response to meropenem 200 mg/kg subcutaneously every 6 h (q6h). Pharmacodynamic analyses were performed by transforming drug exposure from dose (mg/kg) to the fraction of the dosing interval; free meropenem concentrations were >minimum inhibitory concentration (MIC) (
f
T > MIC). AB5075 and the AB5075
Δoxa-23
mutant had a MICs of 32 and 4 mg/L, respectively. The transformants harboring oxacillinases
oxa-24/40
and
oxa-58
had an MIC of 64 mg/L. The metallo-β-lactamases
imp-1
,
vim-2
, and
ndm-1
had MICs of 128, 64, and 64 mg/L, respectively. All vehicle-treated transformants displayed
in vivo
growth in the range of 0.75–1.4 log. The response to meropenem was consistent with the varying
f
T > MIC of the transformants and was readily described by an inhibitory sigmoid
E
max
relationship. Stasis was achieved with a
f
T > MIC of 0.36. These
A. baumannii
transformants are invaluable new tools for the assessment of anti-
Acinetobacter
compounds and provide a new pathway for AMR preparedness.
New evidence supports the prophage origin of RcGTA
Authors: Xu Yongle , Liu Binbin , Jiao Nianzhi , Liu Jihua , Chen Feng
Published: August 2024

Gene transfer agents (GTAs) are phage-like entities that package and transfer random host genome fragments between prokaryotes. RcGTA, produced by
Rhodobacter capsulatus
, is hypothesized to originate from a prophage ancestor. Most of the evidence supporting this hypothesis came from the finding of RcGTA-like genes in phages. More than 75% of the RcGTA genes have a phage homolog. However, only a few RcGTA homologs have been identified in a (pro)phage genome, leaving the hypothesis that GTAs evolved from prophages through gene loss with only weak evidence. We herein report the discovery of an inducible prophage (vB_MseS-P1) from a
Mesorhizobium sediminum
strain that contains the largest number (12) of RcGTA homologs found in a phage genome to date. We also identified three putative prophages and two prophage remnants harboring 12–14 RcGTA homologs in a
Methylobacterium nodulans
strain. The protein remote homology detection also revealed more RcGTA homologs from other phages than we previously thought. Moreover, the head–tail gene architecture of these newly discovered prophage-related elements closely resembles that of RcGTA. Furthermore, vB_MseS-P1 virions have structural proteins similar to RcGTA particles. Close phylogenetic relationships between certain prophage genes and RcGTA-like genes in Alphaproteobacteria further support the shared ancestry between RcGTA and prophages. Our findings provide new relatively direct evidence of the origin of RcGTA from a prophage progenitor.

IMPORTANCE

GTAs are important genetic elements in certain groups of bacteria and contribute to the genetic diversification, evolution, and ecological adaptation of bacteria. RcGTA, a common type of GTA, is known to package and transfer random fragments of the bacterial genome to recipient cells. However, the origin of RcGTA is still elusive. It has been hypothesized that RcGTA evolved from a prophage ancestor through gene loss. However, the few RcGTA homologs identified in a (pro)phage genome leave the hypothesis lacking direct evidence. This study uncovers the presence of a large number of RcGTA homologs in an inducible prophage and several putative prophages. The similar head–tail gene architecture and structural protein compositions of these newly discovered prophage-related elements and RcGTA further demonstrate an unprecedentedly observed close evolutionary relationship between prophages and RcGTA. Together, our findings provide more direct evidence supporting the origin of RcGTA from prophage.
Complete genome sequences of
Clostridium perfringens
CP201 isolated from an asymptomatic rhesus monkey (
Macaca mulatta
)
Authors: Kim Sung Guk , Wang Sharon X. , Park Miseon , Min Seonggi , Foley Steven L.
Published: August 2024

Clostridium perfringens
is a leading cause of human gastroenteritis. The genome sequence of
C. perfringens
CP201 from an asymptomatic rhesus monkey,
Macaca mulatta
, consists of one chromosome (3,241,413 bp; 30.22% G + C) and one plasmid (92,983 bp; 28.43% G + C), encoding 2,935 genes, 94 tRNAs, 30 rRNAs, and 1 CRISPR array.
Identification and characterization of archaeal-type FAD synthase as a novel tractable drug target from the parasitic protozoa
Entamoeba histolytica
Authors: Wulansari Dewi , Jeelani Ghulam , Yazaki Euki , Nozaki Tomoyoshi
Published: August 2024

Flavin adenine dinucleotide (FAD) is an essential cofactor for numerous flavoenzymes present in all living organisms. The biosynthesis of FAD from riboflavin involves two sequential reactions catalyzed by riboflavin kinase and flavin adenine dinucleotide synthase (FADS).
Entamoeba histolytica
, the protozoan parasite responsible for amebiasis, apparently lacks a gene encoding FADS that share similarity with bacterial and eukaryotic canonical FADS, yet it can synthesize FAD. In this study, we have identified the gene responsible for FADS and thoroughly characterized physiological and biochemical properties of FADS from
E. histolytica
. Phylogenetic analysis revealed that the gene was likely laterally transferred from archaea. The kinetic properties of recombinant EhFADS were consistent with the notion that EhFADS is of archaeal origin, exhibiting
K
M
and
k
cat
values similar to those of the arachaeal enzyme while significantly differing from the human counterpart. Repression of gene expression of
EhFADS
by epigenetic gene silencing caused substantial reduction in FAD levels and parasite growth, underscoring the importance of EhFADS for the parasite. Furthermore, we demonstrated that
EhFADS
gene silencing reduced thioredoxin reductase activity, which requires FAD as a cofactor and makes the ameba more susceptible to metronidazole. In summary, this study unveils unique evolutionary and biochemical features of EhFADS and underscores its significance as a promising drug target in combating human amebiasis.

IMPORTANCE

FAD is important for all forms of life, yet its role and metabolism are still poorly studied in
E. histolytica
, the protozoan parasite causing human amebiasis. Our study uncovers the evolutionary unique key enzyme, archaeal-type FADS for FAD biosynthesis from
E. histolytica
for the first time. Additionally, we showed the essentiality of this enzyme for parasite survival, highlighting its potential as target for drug development against
E. histolytica
infections.
Transcription factors containing both C
2
H
2
and homeobox domains play different roles in
Verticillium dahliae
Authors: Tang Chen , Wang Haifeng , Jin Xianjiang , Li Wenwen , Wang Yonglin
Published: August 2024

Verticillium dahliae
causes Verticillium wilt in more than 200 plant species worldwide. As a soilborne fungus, it forms melanized microsclerotia and colonizes the xylem of host plants. Our previous study revealed a subfamily of C
2
H
2
-homeobox transcription factors in
V. dahliae
, but their biological roles remain unknown. In this study, we systematically characterized the functions of seven C
2
H
2
-homeobox transcription factors in
V. dahliae
. Deletion of
VdChtf3
and
VdChtf6
significantly decreased the production of melanized microsclerotia, and knockout of
VdChtf1
and
VdChtf4
enhanced virulence. Loss of
VdChtf2
and
VdChtf6
increased conidium production, whereas loss of
VdChtf5
and
VdChtf7
did not affect growth, conidiation, microsclerotial formation, or virulence. Further research showed that VdChtf3 activated the expression of genes encoding pectic enzymes to participate in microsclerotial formation. In addition, VdChtf4 reduced the expression of
VdSOD1
to disturb the scavenging of superoxide radicals but induced the expression of genes related to cell wall synthesis to maintain cell wall integrity. These findings highlight the diverse roles of different members of the C
2
H
2
-homeobox gene family in
V. dahliae
.

IMPORTANCE

Verticillium dahliae
is a soilborne fungus that causes plant wilt and can infect a variety of economic crops and woody trees. The molecular basis of microsclerotial formation and infection by this fungus remains to be further studied. In this study, we analyzed the functions of seven C2H2-homobox transcription factors. Notably, VdChtf3 and VdChtf4 exhibited the most severe defects, affecting phenotypes associated with critical developmental stages in the
V. dahliae
disease cycle. Our results indicate that VdChtf3 is a potential specific regulator of microsclerotial formation, modulating the expression of pectinase-encoding genes. This finding could contribute to a better understanding of microsclerotial development in
V. dahliae
. Moreover, VdChtf4 was associated with cell wall integrity, reactive oxygen species (ROS) stress resistance, and increased virulence. These discoveries shed light on the biological significance of C2H2-homeobox transcription factors in
V. dahliae
's adaptation to the environment and infection of host plants.
Investigating group A
Streptococcus
antibiotic tolerance in necrotizing fasciitis
Authors: Keller Nadia , Boumasmoud Mathilde , Andreoni Federica , Tarnutzer Andrea , von Matt Manuela , Scheier Thomas C. , Epprecht Jana , Weller David , Gómez-Mejia Alejandro , Huemer Markus , von Reibnitz Donata , Fontein Duveken B. Y. , Marques-Maggio Ewerton , Schuepbach Reto A. , Mairpady-Shambat Srikanth , Brugger Silvio D. , Zinkernagel Annelies S.
Published: August 2024

Group A
Streptococcus
(GAS) necrotizing fasciitis (NF) is a difficult-to-treat bacterial infection associated with high morbidity and mortality despite extensive surgery and targeted antibiotic treatment. Difficult-to-treat infections are often characterized by the presence of bacteria surviving prolonged antibiotic exposure without displaying genetic resistance, referred to as persisters. In the present study, we investigated the presence of GAS persisters in tissue freshly debrided from patients as well as in an
in vivo
mouse model of NF and examined the phenomenon of antibiotic tolerance. Time-lapse imaging of GAS plated directly upon isolation from NF debrided tissue and an antibiotic challenge-based persisters assay were used to assess the presence of persisters. We show for the first time that GAS recovered directly from freshly debrided NF tissue is characterized by heterogeneous and overall delayed colony appearance time, suggesting the presence of persisters. Acidic pH or nutrient stress exposure, mimicking the NF-like environment
in vitro
, led to a similar phenotypic heterogeneity and resulted in enhanced survival upon antibiotic challenge, confirming the presence of GAS persisters. GAS persisters might contribute to NF treatment failure, despite extensive surgery and adequate antibiotic treatment.

IMPORTANCE

Difficult-to-treat and recurrent infections are a global problem burdening society and the health care system alike. Unraveling the mechanisms by which bacteria can survive antibiotic treatment without developing genetic resistance is of utmost importance to lay the foundation for new, effective therapeutic approaches. For the first time, we describe the phenomenon of antibiotic tolerance in group A
Streptococcus
(GAS) isolated from necrotizing fasciitis (NF) patients. Dormant, non-replicating cells (persisters) are tolerant to antibiotics and their occurrence
in vivo
is reported in an increasing number of bacterial species. Tailored treatment options, including the use of persisters-targeting drugs, need to be developed to specifically target dormant bacteria causing difficult-to-treat and recurrent infections.
Minimal transcriptional regulation of horizontally transferred photosynthesis genes in phototrophic bacterium
Gemmatimonas phototrophica
Authors: Kopejtka Karel , Tomasch Jürgen , Shivaramu Sahana , Saini Mohit Kumar , Kaftan David , Koblížek Michal
Published: August 2024

The first phototrophic member of the bacterial phylum
Gemmatimonadota
,
Gemmatimonas phototrophica
AP64
T
, received all its photosynthesis genes via distant horizontal gene transfer from a purple bacterium. Here, we investigated how these acquired genes, which are tightly controlled by oxygen and light in the ancestor, are integrated into the regulatory system of its new host.
G. phototrophica
grew well under aerobic and semiaerobic conditions, with almost no difference in gene expression. Under aerobic conditions, the growth of
G. phototrophica
was optimal at 80 µmol photon m
−2
s
−1
, while higher light intensities had an inhibitory effect. The transcriptome showed only a minimal response to the dark–light shift at optimal light intensity, while the exposure to a higher light intensity (200 µmol photon m
−2
s
−1
) induced already stronger but still transient changes in gene expression. Interestingly, a singlet oxygen defense was not activated under any conditions tested. Our results indicate that
G. phototrophica
possesses neither the oxygen-dependent repression of photosynthesis genes known from purple bacteria nor the light-dependent repression described in aerobic anoxygenic phototrophs. Instead,
G. phototrophica
has evolved as a low-light species preferring reduced oxygen concentrations. Under these conditions, the bacterium can safely employ its photoheterotrophic metabolism without the need for complex regulatory mechanisms.

IMPORTANCE

Horizontal gene transfer is one of the main mechanisms by which bacteria acquire new genes. However, it represents only the first step as the transferred genes have also to be functionally and regulatory integrated into the recipient’s cellular machinery.
Gemmatimonas phototrophica
, a member of bacterial phylum Gemmatimonadota, acquired its photosynthesis genes via distant horizontal gene transfer from a purple bacterium. Thus, it represents a unique natural experiment, in which the entire package of photosynthesis genes was transplanted into a distant host. We show that
G. phototrophica
lacks the regulation of photosynthesis gene expressions in response to oxygen concentration and light intensity that are common in purple bacteria. This restricts its growth to low-light habitats with reduced oxygen. Understanding the regulation of horizontally transferred genes is important not only for microbial evolution but also for synthetic biology and the engineering of novel organisms, as these rely on the successful integration of foreign genes.
Characterization of novel double-reporter strains of
Mycobacterium abscessus
for drug discovery: a study in mScarlet
Authors: Bento Clara M. , van Calster Kevin , Piller Tatiana , Oliveira Gabriel S. , de Vooght Linda , Cappoen Davie , Cos Paul , Gomes M. Salomé , Silva Tânia
Published: August 2024

Mycobacterium abscessus
(Mab) is an emerging pathogen that poses a severe health threat, especially in people with cystic fibrosis and other chronic lung diseases. Available drugs are largely ineffective due to an exquisite intrinsic resistance, making Mab infections only comparable to multidrug-resistant tuberculosis. Current treatment is based on lengthy multidrug therapy, complicated by poor outcomes and high rates of treatment failure, recurrence, and mortality. Thus, finding new and more efficient drugs to combat this pathogen is urgent. However, drug discovery efforts targeting Mab have been limited, and traditional drug screening methods are labor-intensive, low-throughput, and do not reflect clinical effectiveness. Therefore, this work aimed to develop a new, efficient, and reliable tool for drug screening against Mab that can be used
in vitro
for identifying hits in a high-throughput manner and
in vivo
to select drug candidates for future clinical trials. We engineered two stable double-reporter strains of Mab capable of emitting strong fluorescent and luminescent signals. This is due to the expression of mScarlet protein and luciferase enzyme or the entire lux operon. Importantly, these strains maintain the same ground characteristics as the non-transformed Mab strain. We show that these new strains can be applied to various setups, from MIC determination in broth cultures and macrophage infection assays to
in vivo
infection (using the
Galleria mellonella
model). Using these strains enhances the potential for high-throughput screening of thousands of compounds in a fast and reliable way.

IMPORTANCE

Mycobacterium abscessus
(Mab) is currently considered an “incurable nightmare.” Its intrinsic resistance, high toxicity, long duration, and low cure rates of available therapies often lead to the clinical decision not to treat. Moreover, one of the significant drawbacks of anti-Mab drug development is the lack of correlation between
in vitro
susceptibility and clinical efficacy. Most drug screening assays are performed on Mab growing in liquid cultures. But being an intracellular pathogen, inducing granulomas and biofilm formation, the broth culture is far from ideal as
in vitro
drug-testing setup. This study presents new double-reporter Mab strains that allow direct real-time bacterial detection and quantification in a non-invasive way. These strains can be applied to an extensive range of experimental settings, far surpassing the utility of single-reporter bacteria. They can be used in all steps of the pre-clinical anti-Mab drug development pipeline, constituting a highly valuable tool to increase its success.
Topological Levinson’s theorem in presence of embedded thresholds and discontinuities of the scattering matrix: A quasi-1D example
Authors: Austen V. , Parra D. , Rennie A. , Richard S.
Published: August 2024

A family of quasi-[Formula: see text]D Schrödinger operators is investigated through scattering theory. The continuous spectrum of these operators exhibits changes of multiplicity, and some of these operators possess resonances at thresholds. It is shown that the corresponding wave operators belong to an explicitly constructed [Formula: see text]-algebra. The quotient of this algebra by the ideal of compact operators is studied, and an index theorem is deduced from these investigations. This result corresponds to a topological version of Levinson’s theorem in the presence of embedded thresholds, resonances, and changes of multiplicity of the scattering matrices. In the last two sections of the paper, the [Formula: see text]-theory of the main [Formula: see text]-algebra and the dependence on an external parameter are carefully analyzed. In particular, a surface of resonances is exhibited, probably for the first time. The contents of these two sections are of independent interest, and the main result does not depend on them.
HeadShift: Head Pointing with Dynamic Control-Display Gain
Authors: Wang Haopeng , Sidenmark Ludwig , Weidner Florian , Newn Joshua , Gellersen Hans
Published: August 2024

Head pointing is widely used for hands-free input in head-mounted displays (HMDs). The primary role of head movement in an HMD is to control the viewport based on absolute mapping of head rotation to the 3D environment. Head pointing is conventionally supported by the same 1:1 mapping of input with a cursor fixed in the centre of the view, but this requires exaggerated head movement and limits input granularity. In this work, we propose to adopt dynamic gain to improve ergonomics and precision, and introduce the
HeadShift
technique. The design of HeadShift is grounded in natural eye-head coordination to manage control of the viewport and the cursor at different speeds. We evaluated HeadShift in a Fitts’ Law experiment and on three different applications in VR, finding the technique to reduce error rate and effort. The findings are significant as they show that gain can be adopted effectively for head pointing while ensuring that the cursor is maintained within a comfortable eye-in-head viewing range.
Realistic Cost to Execute Practical Quantum Circuits using Direct Clifford+T Lattice Surgery Compilation
Authors: Leblond Tyler , Dean Christopher , Watkins George , Bennink Ryan
Published: August 2024

We report a resource estimation pipeline that explicitly compiles quantum circuits expressed using the Clifford+T gate set into a surface code lattice surgery instruction set. The cadence of magic state requests from the compiled circuit enables the optimization of magic state distillation and storage requirements in a
post-hoc
analysis. To compile logical circuits into lattice surgery operations, we build upon the open-source Lattice Surgery Compiler. The revised compiler operates in two stages: the first translates logical gates into an abstract, layout-independent instruction set; the second compiles these into local lattice surgery instructions that are allocated to hardware tiles according to a specified resource layout. The second stage retains logical parallelism while avoiding resource contention in the fault-tolerant layer, aiding realism. Additionally, users can specify dedicated tiles at which magic states are replenished, enabling resource costs from the logical computation to be considered independently from magic state distillation and storage. We demonstrate the applicability of our pipeline to large practical quantum circuits by providing resource estimates for the ground state estimation of molecules. We find that variable magic state consumption rates in real circuits can cause the resource costs of magic state storage to dominate unless production is varied to suit.
Stacked Classification Approach using Optimized Hybrid Deep Learning Model for Early Prediction of Behaviour Changes on Social Media
Authors: Shukla Shiv Shankar Prasad , Singh Maheshwari Prasad
Published: August 2024

Detecting signs of suicidal thoughts on social media is paramount for preventing suicides, given the platforms' role as primary outlets for emotional expression. Traditional embedding techniques focus solely on semantic analysis and lack the sentiment analysis essential for capturing emotions. This limitation poses challenges in developing high-accuracy models. Additionally, previous studies often rely on a single dataset, further constraining their effectiveness. To overcome these challenges, this study proposes an innovative approach that integrates embedding techniques such as BERT, which offers semantic and syntactic analysis of the posts, with sentiment analysis provided by VADER scores extracted from the VADER sentiment analysis tool. The identified features are then input into the proposed optimised hybrid deep learning model, specifically the Bi-GRU and Attention incorporated with Stacked or Stacking Classifier (Decision Tree, Random Forest, Gradient Boost, as the base classifier and XGBoost as meta classifier), which undergoes optimisation using the grid search technique to enhance detection capabilities. In evaluations, the model achieved an impressive accuracy and F1-score of 98% on the Reddit dataset and 97% on the twitter (formally known as X) dataset. The research evaluates the efficacy of several machine learning models, encompassing Decision Trees, Random Forests, Gradient Boosting, and XGBoost. Moreover, it examines sophisticated models like LSTM with Attention, Bi-LSTM with Attention, and Bi-GRU with Attention, augmented with word embeddings such as BERT, MUSE, and fastText, alongside the fusion of sentiment VADER score. These results emphasise the promise of a holistic strategy that combines advanced feature embedding techniques with semantic features, showcasing a notably efficient detection of suicidal ideation on social media.
The Genetics and Functional Genomics of Osteoarthritis
Authors: Arruda Ana Luiza , Katsoula Georgia , Chen Shibo , Reimann Ene , Kreitmaier Peter , Zeggini Eleftheria
Published: August 2024

Osteoarthritis is the most prevalent whole-joint degenerative disorder, and is characterized by the degradation of articular cartilage and the underlying bone structures. Almost 600 million people are affected by osteoarthritis worldwide. No curative treatments are available, and management strategies focus mostly on pain relief. Here, we provide a comprehensive overview of the available human genetic and functional genomics studies for osteoarthritis to date and delineate how these studies have helped shed light on disease etiopathology. We highlight genetic discoveries from genome-wide association studies and provide a detailed overview of molecular-level investigations in osteoarthritis tissues, including methylation-, transcriptomics-, and proteomics-level analyses. We review how functional genomics data from different molecular levels have helped to prioritize effector genes that can be used as drug targets or drug-repurposing opportunities. Finally, we discuss future directions with the potential to drive a step change in osteoarthritis research.
Somatic Gene Therapy: Ethics and Access
Authors: Bateman-House Alison
Published: August 2024

Manipulation of a patient's genome for therapeutic ends is being attempted through numerous methods, some of which have resulted in disease-modifying interventions. The much anticipated promise of somatic gene therapy is starting to pay off; however, there remain many scientific unknowns, including concerns about safety and durability. A significant ethical concern is that of access to these novel interventions, an issue that is normally framed in terms of the high costs of approved products. I describe how access issues permeate gene therapy long before there is any commercial product and how even upstream decisions—such as choices of indication to pursue, viral vector, and where to site a trial—have significant implications for access to resultant products in both the developmental and commercial stages.
Sickle Cell Anemia Screening in Newborns and Analysis of Haplotypes in Patients from Santiago Island, Cape Verde
Authors: Freire Ariana , Charola-Ramos Laura , González-Guerra Elisa , Gonçalves João , Rocha Vanusa , Afreixo Vera , Martínez-Carretero Enrique , Raya José M.
Published: August 2024

Sickle cell anemia (SCA) results from a mutation in the β‐globin gene, leading to the production of mutant hemoglobin, known as hemoglobin S (HbS). Despite being a genetic disorder, the phenotype of SCA can be influenced by the level of fetal hemoglobin (HbF), which is associated with beta S‐globin haplotypes. In this study, we conducted newborn screening (NBS) using samples collected from umbilical cord blood in two hospitals on Santiago Island, Cape Verde. In newborns, HbS was detected using high‐performance liquid chromatography (HPLC) on dried blood spot, with confirmation through polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). In addition, we assessed the hematological and clinical characteristics of a second population group consisting of patients diagnosed with SCA. Haplotype determination was performed on both newborns with HbS and patients with SCA. Beta S‐globin haplotypes were determined using PCR‐RFLP. Hematological values were analyzed using standard methods. Out of 346 newborns, 21 (6%) were carriers of the sickle cell trait (HbAS) while none were identified as homozygous for sickle cell disease (HbSS). Among both groups of individuals, four haplotypes were identified: Senegal, Arabi‐Indian, Bantu, and Benin. The Senegal haplotype was the most prevalent, possibly reflecting the ethnic origin of the mutations observed. Hematological values did not differ significantly among haplotypes. However, higher levels of HbF were associated with better hematological values. These findings suggest a positive impact of elevated HbF levels on reducing the severity of SCA. Finally, we demonstrated how the combination of technics, HPLC and molecular analysis, provided a consistent and reproducible results that can be used for NBS for SCA.
Possible Implications of Managing Alexithymia on Quality of Life in Parkinson’s Disease: A Systematic Review
Authors: Culicetto Laura , Formica Caterina , Lo Buono Viviana , Latella Desirèe , Maresca Giuseppa , Brigandì Amelia , Sorbera Chiara , Di Lorenzo Giuseppe , Quartarone Angelo , Marino Silvia
Published: August 2024

Alexithymia, characterized by difficulty in recognizing and verbalizing emotions, is reported to be more prevalent in subjects with Parkinson’s disease (PD) than in the general population. Although it is one of the nonmotor symptoms of PD, alexithymia is often overlooked in clinical practice. The aim of this systematic review is to investigate the prevalence of alexithymia in PD, assess its impact on quality of life, and explore the rehabilitation approaches for alexithymia. Research articles, selected from PubMed, Scopus, and Web of Science, were limited to those published in English from 2013 to 2023. The search terms combined were “Alexithymia,” “Parkinson’s disease,”, and “Quality of life.” Current literature review indicates that alexithymia is commonly assessed using the Toronto Alexithymia Scale (TAS‐20), and it is associated with deficits in visuospatial and executive functions. Presently, rehabilitation interventions for alexithymia are scarce, and their effectiveness remains controversial. Future research should focus on developing comprehensive assessments and rehabilitation strategies for emotional processing, considering its significant impact on the quality of life of both patients and caregivers.
Activating the Mobile User Interface With a Rule‐Based Chatbot and EEG‐Based Emotion Recognition to Aid in Coping With Negative Emotions
Authors: Banjar Haneen Reda , Alsefri Lujain , Alshomrani Aseel , Hamdhy Morouj , Alahmari Sara , Sharaf Sanaa
Published: August 2024

Mental health depends on emotional intelligence (EI), the ability to recognize, understand, and manage emotions. As emotions—positive and negative—influence our actions, decisions, and health, EI has become more important in today’s fast‐paced society. Negative emotions, in particular, pose a challenge due to their complexity and the difficulty in managing them effectively. The “Motus Up” mobile app represents a significant leap in personal mental health management by merging EEG‐based emotion recognition with a rule‐based chatbot to aid users in managing negative emotions. Utilizing principles of EI, the app customizes the mobile interface color settings, suggesting activities and providing advice suited to the user’s emotional state confirmed by the chatbot. The emotion recognition model is trained and tested using the SEED‐IV dataset, ensuring compatibility with consumer EEG headbands and accurate detection of complex emotions like sadness and fear. Thorough static and dynamic testing has validated the app’s design and operational efficacy, confirming its preparedness for practical use. By combining real‐time EEG data analysis with intelligent chatbot interactions, “Motus Up” stands out as an innovative mental health tool that enhances EI and offers a responsive experience for emotional self‐regulation. This integration of technology and psychology in a mobile platform is poised to improve mental well‐being and EI on a personal scale.
Supplementary Figure S5 from ANGPTL4 Suppresses Clear Cell Renal Cell Carcinoma via Inhibition of Lysosomal Acid Lipase
Authors: Jin Zeng , De Umasankar , Tithi Tanzia Islam , Kleberg Jeremy , Nataraj Akhila , Jolley Elena , Carelock Madison E. , Davies Brandon S. , Zhang Weizhou , Kolb Ryan
Published: August 2024

Supplementary Figure S5
Supplementary Figure S1 from ANGPTL4 Suppresses Clear Cell Renal Cell Carcinoma via Inhibition of Lysosomal Acid Lipase
Authors: Jin Zeng , De Umasankar , Tithi Tanzia Islam , Kleberg Jeremy , Nataraj Akhila , Jolley Elena , Carelock Madison E. , Davies Brandon S. , Zhang Weizhou , Kolb Ryan
Published: August 2024

Supplementary Figure S1
Figure 4 from ANGPTL4 Suppresses Clear Cell Renal Cell Carcinoma via Inhibition of Lysosomal Acid Lipase
Authors: Jin Zeng , De Umasankar , Tithi Tanzia Islam , Kleberg Jeremy , Nataraj Akhila , Jolley Elena , Carelock Madison E. , Davies Brandon S. , Zhang Weizhou , Kolb Ryan
Published: August 2024

Loss of ANGPTL4 is associated with enrichment for lipid metabolism genes. A, Volcano plot for CAKi1 A4KO versus WT cells. Genes with an absolute value log2 fold change ≥1 and an adjusted P value of ≤0.05 are indicated. Genes upregulated in A4 KO cells are red and genes downregulated in A4KO cells are blue. B, GSEA was performed for CAKi-1 A4KO and WT cells. Graph depicts the nominal enrichment score (NES) of gene sets related to metabolism that were enriched—had a FDR <0.25—with A4KO cells. The nominal P value is indicated by the heat bar. Gray bars had a nominal P value that was lower than the threshold for the package used and thus had a value of 0. C, Enrichment plot for the indicated gene set from the GSEA analysis in B. The FDR and nominal P value are indicated. D, Heatmap of the genes in the gene set from C, for CAKi-1 A4KO and WT cells. E, GSEA analysis was performed for 786O A4KO and WT cells. Enrichment plot for the indicated gene set showing enrichment in A4KO cells. The FDR and nominal P value are indicated. F, Graphs depict the average mRNA expression relative to PPIA of the indicated genes in CAKi-1 WT and A4KO cells ± SD. Welch’s t test was done to determine significance.
Impact of new diagnostic criteria on the frequency of diabetes mellitus and prediabetic conditions
Authors: Güney Engin , Özgenb A. Gökhan , Kısakolb Gürcan
Published: August 2024

The American Diabetes Association (ADA) approved new diagnostic criteria for diabetes mellitus in
1997. Altering the diagnostic criteria may result in variable effects on the prevalence of diabetes. In this
study, we aimed to evaluate the difference between World Health Organisation (WHO) and ADA
criteria in practice and the impact of new criteria on the frequency of diabetes mellitus and prediabetic
conditions in patients who need to have their glucose metabolism evaluated.

Two hundred and fifty patients (182 females and 68 males, age 53.1 ± 11.6 years) who were not known
to be diabetic were studied. Subjects with a fasting plasma glucose level of 110 mg/dl and above, or
with a fasting plasma glucose of 100-109 mg/dl and a risk factor were included in the study. An oral
glucose tolerance test with 75 g glucose was performed on all patients. The diagnoses of diabetes,
impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) as defined by two different sets of
criteria were compared.

When patients were evaluated according to WHO criteria, 115 patients (46.0 %) had normal glucose
tolerance, 76 (30.4 %) had IGT and 59 (23.6 %) were diabetic. When patients were evaluated according
to ADA criteria, only 19 patients (7.6 %) had normal glucose tolerance, 52 (20.8 %) had IGT, 113
(45.2 %) had diabetes mellitus (DM) and 66 (26.4 %) patients had IFG. There is an important
difference in the diagnosis of patients (κ=0.45). The most striking difference is in the group that has
fasting plasma glucose between 110-125 mg/dl, especially because of the definition of IFG in the new
criteria.

In conclusion, use of the ADA criteria caused an evident change in the frequency of diabetes mellitus
and prediabetic conditions in the study population. These results suggest that the new criteria are more
sensitive and useful in diagnosing diabetes and especially prediabetic conditions, and also can be
applied more easily. This study only considers patients who needed the evaluation of glucose
metabolism. Further studies are needed to evaluate the change in frequency in similar populations.
Prevention of diabetic foot ulcers: Holy grail of foot clinics
Authors: Rathur H. , Rajbhandari S.M.
Published: August 2024

Diabetic foot ulcer is a common and debilitating complication of diabetes. Often this is preventable by regular screening and
addressing risk factors such as regular podiatry, good foot wear and early consultation with health care professionals. General
measures such as good glycaemic control, prevention of cardiovascular risk factors and prevention of deformity should be
aimed during the early stages of the disease. Diabetic subjects should be encouraged to actively participate in their foot care.
Prevention of foot ulcers will reduce the rate of amputation, which is common in diabetic subjects.
Antepartum pudendal neuropathy and the effect of vaginal delivery in women with type 1 diabetes mellitus in pregnancy
Authors: Mahony Rhona , O’ Brien Conor , Kinsley Brendan , Firth Richard , Coffey Mary , O’Connell Ronan , O‘Herlihy Colm
Published: August 2024

Vaginal delivery is associated with a significant risk of pelvic floor neuropathy and anal sphincter dysfunction. Because
insulin-dependent diabetes mellitus (IDDM) predisposes to neuropathy, our aim was to determine the incidence of pudendal
nerve dysfunction in a cohort of pregnant insulin-dependent diabetic patients and to examine the effect of vaginal delivery on
pudendal nerve and anal sphincter function. Materials and Methods: The pudendal nerve was evaluated using
electromyography of the anal sphincter (EMG) and clitoral anal reflex (CAR) assessment, during the third trimester in 16
pregnant insulin-dependent diabetic women. Upper limb neurological assessment included median motor, ulnar f-wave,
median and ulnar sensory nerve and median transpalmar nerve conduction studies, while the lower limbs were assessed using
tibial motor and f-wave studies. Anal manometry and endoanal ultrasound studies were also performed. Thirteen women
underwent full reassessment at three months postpartum. Results: An increased sensory threshold (>9mA) on CAR was
demonstrable antenatally in 5 women on the right and 8 on the left. Seven women showed prolonged distal latency (>42ms)
on the right and in 8 on the left. Five women showed prolongation of median transpalmar nerve conduction studies (>2.2ms),
which was associated with diabetes of greater than 12 years duration (p=0.029). The median squeeze pressure was 129mmHg
and median resting pressure was 62mmHg. There were no significant changes in nerve conduction or anal manometric
pressures postnatally. Discussion: Pregnant women with type 1 IDDM exhibit subtle changes of axonal neuropathy and
demyelination, but we found no increased susceptibility to pudendal nerve injury during vaginal childbirth. (Int J Diabetes
Metab 14: 82-86, 2006 )