bluuebunny/crossref_metadata_2025 huggingface dataset:
Directional reverberation time and the image source method for rectangular parallelepipedal rooms
Authors: Bilbao Stefan , Alary Benoit
Published: February 2024

The image source (IS) method is a commonly used geometrical acoustics simulation technique in room and virtual acoustics. In particular, it has been used in the analysis of room reverberation under different choices of geometry and wall conditions. Under a simple rectangular parallelepipedal geometry, reverberation time is known to be dependent on the direction of arrival of reflections relative to the room axes. In this article, a closed-form expression for the directional energy decay and reverberation time is derived, which is valid in the late response, and may be used in the case of either angle-independent or angle-dependent reflection. The expression reduces to an easily evaluated formula in the case of an omnidirectional energy decay curve (EDC). Various numerical results are presented, including the validation of the closed-form expression against EDCs and late reverberation times drawn directly from the IS method.
A mechanism of lysosomal calcium entry
Authors: Zajac Matthew , Mukherjee Sourajit , Anees Palapuravan , Oettinger Daphne , Henn Katharine , Srikumar Jainaha , Zou Junyi , Saminathan Anand , Krishnan Yamuna
Published: February 2024

Lysosomal calcium (Ca
2+
) release is critical to cell signaling and is mediated by well-known lysosomal Ca
2+
channels. Yet, how lysosomes refill their Ca
2+
remains hitherto undescribed. Here, from an RNA interference screen in
Caenorhabditis elegans
, we identify an evolutionarily conserved gene,
lci-1
, that facilitates lysosomal Ca
2+
entry in
C. elegans
and mammalian cells. We found that its human homolog TMEM165, previously designated as a Ca
2+
/H
+
exchanger, imports Ca
2+
pH dependently into lysosomes. Using two-ion mapping and electrophysiology, we show that TMEM165, hereafter referred to as human LCI, acts as a proton-activated, lysosomal Ca
2+
importer. Defects in lysosomal Ca
2+
channels cause several neurodegenerative diseases, and knowledge of lysosomal Ca
2+
importers may provide previously unidentified avenues to explore the physiology of Ca
2+
channels.
Large-scale smart bioreactor with fully integrated wireless multivariate sensors and electronics for long-term in situ monitoring of stem cell culture
Authors: Lee Jimin , Kim Hojoong , Lim Hyo-Ryoung , Kim Yun Soung , Hoang Thi Thai Thanh , Choi Jeongmoon , Jeong Gun-Jae , Kim Hodam , Herbert Robert , Soltis Ira , Kim Ka Ram , Lee Sung Hoon , Kwon Youngjin , Lee Yunki , Jang Young Charles , Yeo Woon-Hong
Published: February 2024

Achieving large-scale, cost-effective, and reproducible manufacturing of stem cells with the existing devices is challenging. Traditional single-use cell-bag bioreactors, limited by their rigid and single-point sensors, struggle with accuracy and scalability for high-quality cell manufacturing. Here, we introduce a smart bioreactor system that enables multi-spatial sensing for real-time, wireless culture monitoring. This scalable system includes a low-profile, label-free thin-film sensor array and electronics integrated with a flexible cell bag, allowing for simultaneous assessment of culture properties such as pH, dissolved oxygen, glucose, and temperature, to receive real-time feedback for up to 30 days. The experimental results show the accurate monitoring of time-dynamic and spatial variations of stem cells and myoblast cells with adjustable carriers from a plastic dish to a 2-liter cell bag. These advances open up the broad applicability of the smart sensing system for large-scale, lower-cost, reproducible, and high-quality engineered cell manufacturing for broad clinical use.
Acoustic hologram–induced virtual in vivo enhanced waveguide (AH-VIEW)
Authors: Lin Qibo , Li Zhaoxi , Wang Bo , Zhou Mengqing , Xie Yang , Wang Danfeng , Hou Chenxue , Wang Runyu , Liu Xiangdong , Sun Xin , Shan Han , Chen Ziyan , Wu Huayi , Yang Yintang , Fei Chunlong , Chen Zeyu
Published: February 2024

Optical imaging and phototherapy in deep tissues face notable challenges due to light scattering. We use encoded acoustic holograms to generate three-dimensional acoustic fields within the target medium, enabling instantaneous and robust modulation of the volumetric refractive index, thereby noninvasively controlling the trajectory of light. Through this approach, we achieved a remarkable 24.3% increase in tissue heating rate in vitro photothermal effect tests on porcine skin. In vivo photoacoustic imaging of mouse brain vasculature exhibits an improved signal-to-noise ratio through the intact scalp and skull. These findings demonstrate that our strategy can effectively suppress light scattering in complex biological tissues by inducing low-angle scattering, achieving an effective depth reaching the millimeter scale. The versatility of this strategy extends its potential applications to neuroscience, lithography, and additive manufacturing.
Arylgold nanoclusters: Phenyl-stabilized Au
44
with thermal-controlled NIR single/dual-channel phosphorescence
Authors: Si Wei-Dan , Zhang Chengkai , Zhou Meng , Wang Zhi , Feng Lei , Tung Chen-Ho , Sun Di
Published: February 2024

Arylation of gold holds paramount importance in the domain of organometallic chemistry; however, the exploration of arylgold nanoclusters remains in its infancy primarily due to the synthetic challenge. Here, we present a facile and effective arylation strategy to directly synthesize two arylgold nanoclusters (
Au44a
and
Au44b
), by using tetraarylborates, capable of transferring aryl fragments to metal centers. X-ray crystallography reveals that both Au
44
nanoclusters contain an Au
44
kernel co-protected by six aryl groups, two tetrahydrothiophene, and 16 alkynyl-ether ligands, the latter is generated in situ through Williamson ether reaction during the assembly processes. Notably, Au
44
nanoclusters exhibit near-infrared (NIR) phosphorescence (λ
max
= 958 nm) and microsecond radiative relaxation at ambient condition, which is a thermal-controlled single/dual-channel phosphorescent emission revealed by temperature-dependent NIR, time-resolved emission, and femtosecond/nanosecond transition absorption spectra. This work represents a breakthrough in using aryl as protective ligands for the construction of gold nanoclusters, which is poised to have a transformative impact on organometallic nanoclusters.
Human-scale navigation of magnetic microrobots in hepatic arteries
Authors: Li Ning , Fei Phillip , Tous Cyril , Rezaei Adariani Mahdi , Hautot Marie-Lou , Ouedraogo Inès , Hadjadj Amina , Dimov Ivan P. , Zhang Quan , Lessard Simon , Nosrati Zeynab , Ng Courtney N. , Saatchi Katayoun , Häfeli Urs O. , Tremblay Charles , Kadoury Samuel , Tang An , Martel Sylvain , Soulez Gilles
Published: February 2024

Using external actuation sources to navigate untethered drug-eluting microrobots in the bloodstream offers great promise in improving the selectivity of drug delivery, especially in oncology, but the current field forces are difficult to maintain with enough strength inside the human body (>70-centimeter-diameter range) to achieve this operation. Here, we present an algorithm to predict the optimal patient position with respect to gravity during endovascular microrobot navigation. Magnetic resonance navigation, using magnetic field gradients in clinical magnetic resonance imaging (MRI), is combined with the algorithm to improve the targeting efficiency of magnetic microrobots (MMRs). Using a dedicated microparticle injector, a high-precision MRI-compatible balloon inflation system, and a clinical MRI, MMRs were successfully steered into targeted lobes via the hepatic arteries of living pigs. The distribution ratio of the microrobots (roughly 2000 MMRs per pig) in the right liver lobe increased from 47.7 to 86.4% and increased in the left lobe from 52.2 to 84.1%. After passing through multiple vascular bifurcations, the number of MMRs reaching four different target liver lobes had a 1.7- to 2.6-fold increase in the navigation groups compared with the control group. Performing simulations on 19 patients with hepatocellular carcinoma (HCC) demonstrated that the proposed technique can meet the need for hepatic embolization in patients with HCC. Our technology offers selectable direction for actuator-based navigation of microrobots at the human scale.
An adapted method for Cas9-mediated editing reveals the species-specific role of β-glucoside utilization driving competition between
Klebsiella
species
Authors: Almási Éva d. H. , Knischewski Nele , Osbelt Lisa , Muthukumarasamy Uthayakumar , El Mouali Youssef , Vialetto Elena , Beisel Chase L. , Strowig Till
Published: February 2024

Cas9-based gene editing tools have revolutionized genetics, enabling the fast and precise manipulation of diverse bacterial species. However, widely applicable genetic tools for non-model gut bacteria are unavailable. Here, we present a two-plasmid Cas9-based system designed for gene deletion and knock-in complementation in three members of the
Klebsiella oxytoca
species complex (KoSC), which we applied to study the genetic factors underlying the role of these bacteria in competition against
Klebsiella pneumoniae
. Firstly, the system allowed efficient and precise full-length gene deletion via enhanced lambda Red expression. Furthermore, we tested the efficiency of two independent, functionally validated complementation strategies. Ultimately, the insertion of universal “bookmark” targets during gene deletion subsequently allows the most optimal genetic complementation in
K. oxytoca
,
Klebsiella michiganensis
, and
Klebsiella grimontii
. This approach offers a significant advantage by enabling the use of a single high-efficiency “bookmark” for complementing other loci or strains, eliminating the need for site-specific design. We revealed that the carbohydrate permease CasA is critical in
ex vivo
assays for
K. pneumoniae
inhibition by
K. oxytoca
but is neither sufficient nor required for
K. michiganensis
and
K. grimontii
. Thus, the adaptation of state-of-the-art genetic tools to KoSC allows the identification of species-specific functions in microbial competition.

IMPORTANCE

Cas9-based gene editing tools have revolutionized bacterial genetics, yet, their application to non-model gut bacteria is frequently hampered by various limitations. We utilized a two-plasmid Cas9-based system designed for gene deletion in
Klebsiella pneumoniae
and demonstrate after optimization its utility for gene editing in three members of the
Klebsiella oxytoca
species complex (KoSC) namely
K. oxytoca
,
Klebsiella michiganensis
, and
Klebsiella grimontii
. We then adapted a recently developed protocol for functional complementation based on universal “bookmark” targets applicable to all tested species. In summary, species-specific adaptation of state-of-the-art genetic tools allows efficient gene deletion and complementation in type strains as well as natural isolates of KoSC members to study microbial interactions.
The
ssgB
gene is required for the early stages of sporangium formation in
Actinoplanes missouriensis
Authors: Akutsu Takuya , Tezuka Takeaki , Maruko Manato , Hirata Aiko , Ohnishi Yasuo
Published: February 2024

In
Streptomyces
, multiple paralogs of SsgA-like proteins (SALPs) are involved in spore formation from aerial hyphae. However, the functions of SALPs have not yet been elucidated in other actinobacterial genera. Here, we report the primary function of an SsgB ortholog (AmSsgB) in
Actinoplanes missouriensis
, which develops terminal sporangia on the substrate mycelia via short sporangiophores. Importantly, AmSsgB is the sole SALP in
A. missouriensis
. The transcription of
AmssgB
was upregulated during sporangium formation, consistent with our previous findings that
AmssgB
is a member of the AmBldD regulon. The
AmssgB
null mutant (Δ
AmssgB
) strain formed non-globose irregular structures on the substrate mycelium. Transmission electron microscopy revealed that the irregular structures contained abnormally septate hypha-like cells, without an intrasporangial matrix. These phenotypic changes were restored by complementation with
AmssgB
. Additionally, analysis of the heterologous expression of seven SALP-encoding genes from
Streptomyces coelicolor
A3(2) (
ssgA–G
) in the Δ
AmssgB
strain revealed that only
ssgB
could compensate for AmSsgB deficiency. This indicated that SsgB of
S. coelicolor
A3(2) and AmSsgB have comparable functions in
A. missouriensis
. In contrast to the Δ
AmssgB
strain, the
ftsZ
-disrupted strain showed a severe growth defect and produced small sporangium-like structures that swelled to some extent. These findings indicate that AmSsgB is crucial for the early stages of sporangium formation, not for spore septum formation in the late stages. We propose that AmSsgB is involved in sporangium formation by promoting the expansion of the “presporangium” structures formed on the tips of the substrate hyphae.

IMPORTANCE

SsgB has been proposed as an archetypical SsgA-like protein with an evolutionarily conserved function in the morphological development of spore-forming actinomycetes. SsgB in
Streptomyces coelicolor
A3(2) is involved in spore septum formation. However, it is unclear whether this is the primary function of SsgBs in actinobacteria. This study demonstrated that the SsgB ortholog (AmSsgB) in
Actinoplanes missouriensis
is essential for sporangium expansion, which does not seem to be related to spore septum formation. However, the heterologous expression of
ssgB
from
S. coelicolor
A3(2) restored morphological abnormalities in the Δ
AmssgB
mutant. We propose that the primary function of SsgB is to initiate sporulation in differentiating cells (e.g., aerial hyphae in
Streptomyces
and “presporangium” cells in
A. missouriensis
) although its molecular mechanism remains unknown.
Strain-specific requirements of susceptibility to rhesus enteric calicivirus infection
Authors: Farkas Tibor , Srivastava Vinod
Published: February 2024

Recently, we identified the coxsackie and adenovirus receptor (CAR) as the entry receptor for rhesus enteric calicivirus (ReCV) isolate FT285 and demonstrated that co-expression of the CAR and the type B histo-blood group antigen (HBGA) is required to convert the resistant CHO cell line susceptible to infection. To address whether the CAR is also the functional entry receptor for other ReCV isolates and the requirement for specific HBGAs or other glycans, here we used a panel of recombinant CHO cell lines expressing the CAR and the type A, B, or H HBGAs alone or in combination. Infection studies with three diverse ReCV strains, the prototype GI.1 Tulane virus (TV), GI.2 ReCV-FT285, and GI.3 ReCV-FT7, identified that cell surface expression of the CAR is an absolute requirement for all three strains to promote susceptibility to infection, while the requirement for HBGAs varies among the strains. In addition to the CAR, ReCV-FT285 and TV require type A or B HBGAs for infection. In the absence of HBGAs, TV, but not Re-CV FT285, can also utilize sialic acids, while ReCV-FT7 infection is HBGA-independent and relies on CAR and sialic acid expression. In summary, we demonstrated strain-specific diversity of susceptibility requirements for ReCV infections and that CAR, type A and B HBGA, and sialic acid expression control susceptibility to infection with the three ReCV isolates studied. Our study also indicates that the correlation between
in vitro
HBGA binding and HBGAs required for infection is relatively high, but not absolute. This has direct implications for human noroviruses.

IMPORTANCE

Human noroviruses (HuNoVs) are important enteric pathogens. The lack of a robust HuNoV cell culture system is a bottleneck for HuNoV cell culture-based studies. Often, cell culture-adapted caliciviruses that rapidly replicate in conventional cell lines and recapitulate biological features of HuNoVs are utilized as surrogates. Particularly, rhesus enteric caliciviruses (ReCVs) display remarkable similarities, including the primate host, clinical manifestation of gastroenteritis, genetic/antigenic diversity, and reliance on histo-blood group antigens (HBGAs) for attachment. While the HuNoV entry receptor(s) is unknown, the coxsackie and adenovirus receptor (CAR) has recently been identified as the ReCV entry receptor. Here, we identified the CAR, the type A and B HBGAs, and sialic acids as critical cell surface molecules controlling susceptibility to ReCV infections. The CAR is required for all ReCV isolates studied. However, the requirement for the different carbohydrate molecules varies among different ReCV strains. Our findings have direct implications for HuNoVs.
Bacteriophage and antibiotic combination therapy for recurrent
Enterococcus faecium
bacteremia
Authors: Stellfox Madison E. , Fernandes Carolyn , Shields Ryan K. , Haidar Ghady , Hughes Kramer Kailey , Dembinski Emily , Mangalea Mihnea R. , Arya Garima , Canfield Gregory S. , Duerkop Breck A. , Van Tyne Daria
Published: February 2024

Enterococcus faecium
is a member of the human gastrointestinal (GI) microbiota but can also cause invasive infections, especially in immunocompromised hosts. Enterococci display intrinsic resistance to many antibiotics, and most clinical
E. faecium
isolates have acquired vancomycin resistance, leaving clinicians with a limited repertoire of effective antibiotics. As such, vancomycin-resistant
E. faecium
(VREfm) has become an increasingly difficult to treat nosocomial pathogen that is often associated with treatment failure and recurrent infections. We followed a patient with recurrent
E. faecium
bloodstream infections (BSIs) of increasing severity, which ultimately became unresponsive to antibiotic combination therapy over the course of 7 years. Whole-genome sequencing (WGS) showed that the patient was colonized with closely related
E. faecium
strains for at least 2 years and that invasive isolates likely emerged from a large
E. faecium
population in the patient’s gastrointestinal (GI) tract. The addition of bacteriophage (phage) therapy to the patient’s antimicrobial regimen was associated with several months of clinical improvement and reduced intestinal burden of VRE and
E. faecium. In vitro
analysis showed that antibiotic and phage combination therapy improved bacterial growth suppression compared to therapy with either alone. Eventual
E. faecium
BSI recurrence was not associated with the development of antibiotic or phage resistance in post-treatment isolates. However, an anti-phage-neutralizing antibody response occurred that coincided with an increased relative abundance of VRE in the GI tract, both of which may have contributed to clinical failure. Taken together, these findings highlight the potential utility and limitations of phage therapy to treat antibiotic-resistant enterococcal infections.

IMPORTANCE

Phage therapy is an emerging therapeutic approach for treating bacterial infections that do not respond to traditional antibiotics. The addition of phage therapy to systemic antibiotics to treat a patient with recurrent
E. faecium
infections that were non-responsive to antibiotics alone resulted in fewer hospitalizations and improved the patient's quality of life. Combination phage and antibiotic therapy reduced
E. faecium
and VRE abundance in the patient's stool. Eventually, an anti-phage antibody response emerged that was able to neutralize phage activity, which may have limited clinical efficacy. This study demonstrates the potential of phages as an additional option in the antimicrobial toolbox for treating invasive enterococcal infections and highlights the need for further investigation to ensure phage therapy can be deployed for maximum clinical benefit.
Humoral and cellular immune responses against SARS-CoV-2 post-vaccination in immunocompetent and immunocompromised cancer populations
Authors: Titova Elizabeth , Kan Veronica W. , Lozy Tara , Ip Andrew , Shier Kileen , Prakash Vittal P. , Starolis Meghan , Ansari Sara , Goldgirsh Kira , Kim Seoyeon , Pelliccia Michael C. , Mccutchen Aamirah , Megalla Martinus , Gunning Thomas S. , Kaufman Harvey W. , Meyer William A. , Perlin David S.
Published: February 2024

Cancer patients are at risk for severe coronavirus disease 2019 (COVID-19) outcomes due to impaired immune responses. However, the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is inadequately characterized in this population. We hypothesized that cancer vs non-cancer individuals would mount less robust humoral and/or cellular vaccine-induced immune SARS-CoV-2 responses. Receptor binding domain (RBD) and SARS-CoV-2 spike protein antibody levels and T-cell responses were assessed in immunocompetent individuals with no underlying disorders (
n
= 479) and immunocompromised individuals (
n
= 115). All 594 individuals were vaccinated and of varying COVID-19 statuses (i.e., not known to have been infected, previously infected, or “Long-COVID”). Among immunocompromised individuals, 59% (
n
= 68) had an underlying hematologic malignancy; of those, 46% (
n
= 31) of individuals received cancer treatment <30 days prior to study blood collection. Ninety-eight percentage (
n
= 469) of immunocompetent and 81% (
n
= 93) of immunocompromised individuals had elevated RBD antibody titers (>1,000 U/mL), and of these, 60% (
n
= 281) and 44% (
n
= 41), respectively, also had elevated T-cell responses. Composite T-cell responses were higher in individuals previously infected with SARS-CoV-2 or those diagnosed with Long-COVID compared to uninfected individuals. T-cell responses varied between immunocompetent vs carcinoma (
n
= 12) cohorts (
P
< 0.01) but not in immunocompetent vs hematologic malignancy cohorts. Most SARS-CoV-2 vaccinated individuals mounted robust cellular and/or humoral responses, though higher immunogenicity was observed among the immunocompetent compared to cancer populations. The study suggests B-cell targeted therapies suppress antibody responses, but not T-cell responses, to SARS-CoV-2 vaccination. Thus, vaccination continues to be an effective way to induce humoral and cellular immune responses as a likely key preventive measure against infection and/or subsequent more severe adverse outcomes.

IMPORTANCE

The study was prompted by a desire to better assess the immune status of patients among our cancer host cohort, one of the largest in the New York metropolitan region. Hackensack Meridian Health is the largest healthcare system in New Jersey and cared for more than 75,000 coronavirus disease 2019 patients in its hospitals. The John Theurer Cancer Center sees more than 35,000 new cancer patients a year and performs more than 500 hematopoietic stem cell transplants. As a result, the work was undertaken to assess the effectiveness of vaccination in inducing humoral and cellular responses within this demographic.
Supplemental Material: Reconciling plate motion and faulting at a Rift-Rift-Rift triple junction
Authors: Maestrelli Daniele , al. et
Published: February 2024

The Supplemental Material reports text, table, and figures showing details about analog model setup and scaling, particle image velocimetry analysis, as well as additional comparison with the natural case study.  
Are web-based stress management interventions effective as an indirect treatment for depression? An individual participant data meta-analysis of six randomised trials
Authors: Harrer Mathias , Nixon Patricia , Sprenger Antonia A , Heber Elena , Boß Leif , Heckendorf Hanna , Buntrock Claudia , Ebert David Daniel , Lehr Dirk
Published: February 2024

Question

Depression is highly prevalent and associated with numerous adverse consequences for both individuals and society. Due to low uptake of direct treatment, interventions that target related, but less stigmatising problems, such as perceived stress, have emerged as a new research paradigm.

This individual participant data (IPD) meta-analysis examines if a web-based stress management intervention can be used as an ‘indirect’ treatment of depression.

Study selection and analysis

Bayesian one-stage models were used to estimate pooled effects on depressive symptom severity, minimally important improvement and reliable deterioration. The dose–response relationship was examined using multilevel additive models, and IPD network meta-analysis was employed to estimate the effect of guidance.

Findings

In total, N=1235 patients suffering from clinical-level depression from K=6 randomised trials were included. Moderate-to-large effects were found on depressive symptom severity at 7 weeks post-intervention (d=−0.65; 95% credibility interval (CrI): −0.84 to −0.48) as measured with the Center for Epidemiological Studies’ Depression Scale. Effects were sustained at 3-month follow-up (d=−0.74; 95% CrI: −1.01 to −0.48). Post-intervention symptom severity was linearly related to the number of completed sessions. The incremental impact of guidance was estimated at d=−0.25 (95% CrI: −1.30 to 0.82), with a 35% posterior probability that guided and unguided formats produce equivalent effects.

Conclusions

Our results indicate that web-based stress management can serve as an indirect treatment, yielding effects comparable with direct interventions for depression. Further research is needed to determine if such formats can indeed increase the utilisation of evidence-based treatment, and to corroborate the favourable effects for human guidance.

Study registration

Open material repository: osf.io/dbjc8, osf.io/3qtbe.

Trial registration number

German Clinical Trial Registration (DRKS): DRKS00004749, DRKS00005112, DRKS00005384, DRKS00005687, DRKS00005699, DRKS00005990.
Non-invasive neuromodulation of the right temporoparietal junction using theta-burst stimulation in functional neurological disorder
Authors: Bühler Janine , Weber Samantha , Loukas Serafeim , Walther Sebastian , Aybek Selma
Published: February 2024

Background

Disrupted sense of agency (SoA)—the sense of being the agent of one’s own actions—has been demonstrated in patients with functional neurological disorder (FND), and a key area of the corresponding neuronal network is the right temporoparietal junction (rTPJ). Several functional MRI (fMRI) studies have found hypoactivation as well as hyperactivation of the rTPJ in FND. In a proof-of-concept study, we tested whether repetitive transcranial magnetic stimulation (rTMS) over the rTPJ could restore this aberrant activity.

Methods

In a randomised, crossover, single-blinded, sham-controlled study design, theta-burst stimulation (tb-rTMS) was applied over the rTPJ in 23 patients with FND and 19 healthy controls (HC), with each participant undergoing three stimulatory visits (inhibitory continuous TBS (cTBS), excitatory intermittent TBS (iTBS) and sham). During fMRI, participants played a visuomotor task artificially reducing their SoA (manipulated agency, MA), repeated after each neurostimulation. We compared brain activity and behavioural SoA as primary outcomes before and after tb-rTMS and investigated the feasibility of tb-rTMS over the rTPJ in FND as secondary outcome.

Results

At baseline, patients showed decreased accuracy in detecting reduced agency compared with controls (p<0.001), paralleled by lower brain activation in the rTPJ during MA (p=0.037, volume of interest). A region of interest analysis on the rTPJ showed no effect of the sham condition in FND or HC (p=0.917; p=0.375) but revealed a significant effect of stimulation protocol (cTBS/iTBS, p=0.037) in patients with FND, with the excitatory protocol increasing the blood-oxygen-level-dependent (BOLD) signal, whereas this effect was not found in HC. In neither group, a behavioural effect of tb-rTMS was observed.

Conclusion

Aberrant processing of agency in FND was confirmed at baseline, reflected in behavioural outcome and reduced activity in the rTPJ. Tb-rTMS over this key region elicited neuronal changes in patients, paving ways for future studies exploring TMS as neurobiologically informed intervention to restore SoA in FND. We critically discuss methodological intricacies and outline further steps in this research line.
Is there a role for fibreoptic bronchoscopy in patients presenting with haemoptysis and negative CT? A systematic review and meta-analysis
Authors: Mohammad Syed , Wijayaratne Thisarana , Mavilakandy Akash , Karim Nawazish , Theaker Margaret , Reddy Raja , Tsaknis George
Published: February 2024

Introduction

Haemoptysis can be a feature of lung cancer and patients are typically fast-tracked for evaluation with chest radiography, contrast-enhanced CT and fibreoptic bronchoscopy (FOB).

Objective

We aim to explore whether FOB should be conducted as a component of the routine evaluation of non-massive haemoptysis, especially in the context of suspected lung cancer.

Methods

MEDLINE, EMBASE and Cochrane Library were searched for studies comparing FOB with CT in the evaluation of non-massive haemoptysis while reporting at least one of the listed primary outcomes. Primary outcomes include sensitivity of diagnostic modality with respect to lung cancer. Secondary outcomes include detection of other aetiologies such as infection. Results were synthesised using a random effects meta-analysis. Sensitivity analysis was performed for patient age group and year of study. Risk of bias assessment was carried out with the Quality Assessment of Diagnostic Accuracy Studies-2 tool.

Results

A total of 2273 citations were screened and 11 studies were included, comprising a total sample size of 2015 patients with 226 confirmed cases of lung cancer. A total of 1816 and 1734 patients received a CT scan and FOB, respectively. The pooled sensitivities for detection of lung cancer using CT scan and bronchoscopy were 98% (95% CI 93.0% to 99.0%) and 86% (95% CI 63.0% to 95.0%), respectively. The sensitivity of CT was higher than that of FOB for both primary and secondary outcomes.

Conclusion

This study suggests that bronchoscopy does not offer significant additional diagnostic benefit in the evaluation of patients presenting with non-massive haemoptysis and a negative CT scan.
Diagnostic accuracy of venous system ultrasound for subtypes of acute kidney injury
Authors: Aslaner Mehmet Ali , Helvacı Özant , Haycock Korbin , Kılıçaslan İsa , Yaşar Emre , Cerit Mahi Nur , Şendur Halit Nahit , Güz Galip , Demircan Ahmet
Published: February 2024

Background

Management of acute kidney injury (AKI) in the ED can be difficult due to uncertainty regarding the aetiology. This study investigated the diagnostic value of venous system ultrasound for determining the aetiological subtypes of AKI in the ED.

Methods

This multidisciplinary prospective cohort study was conducted in a single academic ED over the course of a year. Adult patients with AKI were evaluated using the venous excess ultrasound (VExUS) score, which is a four-step ultrasound protocol. The protocol begins with the inferior vena cava (IVC) measurement and examines organ flow patterns, including portal, hepatic and renal veins in the presence of dilated IVC. The AKI subtypes (hypovolaemia, cardiorenal, systemic vasodilatation and renal) were adjudicated by nephrologists and emergency physicians, considering data that became available during the hospitalisation. We determined the diagnostic test characteristics of VExUS for identifying each of the four AKI aetiological subtypes.

Results

150 patients with AKI were included in the study. Hypovolaemia was the most frequent finally adjudicated cause of AKI (66%), followed by cardiorenal (18%), systemic vasodilatation (8.7%) and renal (7.3%). In diagnosing the cardiorenal subtype, the area under the curve (AUC) for VExUS grade >0 was 0.819, with 77.8% sensitivity and 80.5% specificity, and the AUC for IVC maximum diameter >20.4 mm was 0.865, with 74.1% sensitivity and 86.2% specificity. For the hypovolaemia subtype, the AUC for VExUS grade ≤0 was 0.711, with 83.8% sensitivity and 56.9% specificity, and the AUC for IVC maximum diameter ≤16.8 mm was 0.736, with 73.7% sensitivity and 68.6% specificity. None of the parameters achieved adequate test characteristics for renal and systemic vasodilatation subtypes.

Conclusion

The VExUS score has good diagnostic accuracy for cardiorenal AKI and fair accuracy for hypovolaemic AKI but cannot identify renal and systemic vasodilatation subtypes. It should not therefore be used in isolation to determine the cause of AKI in the ED.

Trial registration number

NCT04948710.
Circumstances of unintentional fall-related adult deaths: Utah, 2010–2020
Authors: Shi Yanling , Bennion Erica , Ward Chuck , Nolen Leisha D.
Published: February 2024

Objective

Fall-related deaths have been on the rise nationwide. Our objective was to characterise the trend in unintentional fall-related adult deaths in Utah and evaluate the underlying and contributing causes associated with these deaths.

Methods

We used 2010–2020 Utah death certificate data and included all Utah deaths aged 18 and older with a fall listed on their death records as the underlying or contributing cause of death in the analysis.

Results

From 2010 to 2020, the overall age-adjusted unintentional fall death rate increased 70% from 15.7 to 26.8 per 100 000 person-years, while the overall age-adjusted death rate increase was 12% at the time. On average, the group with falls as one of the contributing causes had 4.9 other contributing causes, while the group with falls as an underlying cause had 3.3; the two averages were statistically different. Incidence of death increased 60% (12.1–19.4 per 100 000) for falls classified as the underlying cause of death and 103% (3.6–7.3 per 100 000) for those with fall as a contributing cause. Coding for the type of fall became more specific with a 30% decrease in unspecified fall (International Classification of Diseases, 10th revision code W19) (5.9–4.1 per 100 000).

Conclusion

There was an increasing trend of unintentional fall-related adult deaths in Utah from 2010 to 2020. This increase is consistent with national trends. Our data supports there is more specific reporting of fall deaths, but better reporting alone cannot explain the uptrend. Furthermore, the deaths with falls as contributing causes increased the most, and these individuals have more comorbidities.
Inadequate prophylaxis in patients with trauma: anti-Xa-guided enoxaparin dosing management in critically ill patients with trauma
Authors: Niziolek Grace Martin , Mangan Lauren , Weaver Cassidi , Prendergast Vanessa , Lamore Raymond , Zielke Megan , Martin Niels D
Published: February 2024

Introduction

Venous thromboembolism (VTE) causes significant morbidity in patients with trauma despite advances in pharmacologic therapy. Prior literature suggests standard enoxaparin dosing may not achieve target prophylactic anti-Xa levels. We hypothesize that a new weight-based enoxaparin protocol with anti-Xa monitoring for dose titration in critically injured patients is safe and easily implemented.

Methods

This prospective observational study included patients with trauma admitted to the trauma intensive care unit (ICU) from January 2021 to September 2022. Enoxaparin dosing was adjusted based on anti-Xa levels as standard of care via a performance improvement initiative. The primary outcome was the proportion of subtarget anti-Xa levels (<0.2 IU/mL) on 30 mg two times per day dosing of enoxaparin. Secondary outcomes included the dosing modifications to attain goal anti-Xa levels, VTE and bleeding events, and hospital and ICU lengths of stay.

Results

A total of 282 consecutive patients were included. Baseline demographics revealed a median age of 36 (26–55) years, and 44.7% with penetrating injuries. Of these, 119 (42.7%) achieved a target anti-Xa level on a starting dose of 30 mg two times per day. Dose modifications for subtarget anti-Xa levels were required in 163 patients (57.8%). Of those, 120 underwent at least one dose modification, which resulted in 78 patients (47.8%) who achieved a target level prior to hospital discharge on a higher dose of enoxaparin. Overall, only 69.1% of patients achieved goal anti-Xa level prior to hospital discharge. VTE occurred in 25 patients (8.8%) and major bleeding in 3 (1.1%) patients.

Conclusion

A majority of critically injured patients do not meet target anti-Xa levels with 30 mg two times per day enoxaparin dosing. This study highlights the need for anti-Xa-based dose modification and efficacy of a pharmacy-driven protocol. Further optimization is warranted to mitigate VTE events.

Level of evidence

Therapeutic/care management, level III
Do we still need Illumina sequencing data? Evaluating Oxford Nanopore Technologies R10.4.1 flow cells and the Rapid v14 library prep kit for Gram negative bacteria whole genome assemblies
Authors: Lerminiaux Nicole , Fakharuddin Ken , Mulvey Michael R. , Mataseje Laura
Published: February 2024

The best whole genome assemblies are currently built from a combination of highly accurate short-read sequencing data and long-read sequencing data that can bridge repetitive and problematic regions. Oxford Nanopore Technologies (ONT) produce long-read sequencing platforms and they are continually improving their technology to obtain higher quality read data that is approaching the quality obtained from short-read platforms such as Illumina. As these innovations continue, we evaluated how much ONT read coverage produced by the Rapid Barcoding Kit v14 (SQK-RBK114) is necessary to generate high-quality hybrid and long-read-only genome assemblies for a panel of carbapenemase-producing Enterobacterales bacterial isolates. We found that 30× long-read coverage is sufficient if Illumina data are available, and that more (at least 100× long-read coverage is recommended for long-read-only assemblies. Illumina polishing is still improving single nucleotide variants (SNVs) and INDELs in long-read-only assemblies. We also examined if antimicrobial resistance genes could be accurately identified in long-read-only data, and found that Flye assemblies regardless of ONT coverage detected >96% of resistance genes at 100% identity and length. Overall, the Rapid Barcoding Kit v14 and long-read-only assemblies can be an optimal sequencing strategy (i.e., plasmid characterization and AMR detection) but finer-scale analyses (i.e., SNV) still benefit from short-read data.
ParticleNet and its application on CEPC jet flavor tagging
Authors: Zhu Yongfeng , Liang Hao , Wang Yuexin , Qu Huilin , Zhou Chen , Ruan Manqi
Published: February 2024

Quarks (except top quarks) and gluons produced in collider experiments hadronize and fragment into sprays of stable particles, called jets. Identification of quark flavor is desired for collider experiments in high-energy physics, relying on flavor tagging algorithms. In this study, using a full simulation of the Circular Electron Positron Collider (CEPC), we investigate the flavor tagging performance of two different algorithms: ParticleNet, based on a Graph Neural Network, and LCFIPlus, based on the Gradient Booted Decision Tree. Compared to LCFIPlus, ParticleNet significantly enhances flavor tagging performance, resulting in a significant improvement in benchmark measurement accuracy, i.e., a 36% improvement for $$\sigma (ZH)\cdot Br(Z\rightarrow \nu \bar{\nu }, H\rightarrow c\bar{c})$$

σ
(
Z
H
)
·
B
r
(
Z
→
ν

ν

¯

,
H
→
c

c

¯

)

measurement and a 75% improvement for $$|V_{cb}|$$

|

V

cb

|

measurement via W boson decay, respectively, when the CEPC operates as a Higgs factory at the center-of-mass energy of 240 GeV and collects an integrated luminosity of 5.6 ab$$^{-1}$$

-
1

. We compare the performance of ParticleNet and LCFIPlus at different vertex detector configurations, observing that the inner radius is the most sensitive parameter, followed by material budget and spatial resolution.
A regularized lattice Boltzmann method based on the multi-layer grid using a buffer scheme
Authors: Liu Zhixiang , Zhao Yunhao , Shi Shaohua , Wang Yang
Published: February 2024

The regularized lattice Boltzmann method (RLBM) has the advantage of improving the accuracy of numerical simulations without increasing the computational overhead. The RLBM usually uses the standard Cartesian grid in numerical simulation. This paper introduces the multi-layer grid technique, the multi-layer grid has different resolutions, which is also more consistent with the physical laws of the flow field. Based on this, a multi-layer grid regularized lattice Boltzmann method (ML-RLBM) for solving complex flow problems is proposed. The proposed method performs local refinement of the grid on the standard Cartesian grid to achieve a multi-layer grid, which can reduce the computational overhead. In order to realize the local grid refinement easily, this paper adopts the center point format to store the multi-layer grid. The ML-RLBM designs a buffer scheme between different layers of grids, which realizes that only spatial interpolation is required at the interface of different layers of grids without temporal interpolation. The numerical results show that the ML-RLBM has excellent numerical accuracy and numerical stability, and it can effectively reduce the computational cost.
Employing CNPS and CPS approaches to calculate numerical roots of ninth-order linear and nonlinear boundary value problems
Authors: Khalid Aasma , Haq Inamul , Rehan Akmal , Alshehri Hashim M. , Osman M. S.
Published: February 2024

The extremely accurate findings of ninth-order linear and nonlinear BVPs are described in this paper. CNPS and CPS are used to find out the numerical roots of linear and nonlinear, ninth-order BVPs. The proposed methods transform the ninth-order BVPs into a system of linear equations. The algorithms developed in this study not only provide approximate solutions to the BVPs using CNPS and CPS, but they also estimate the derivatives from the first to the ninth-order of the analytical solution simultaneously. These approaches are implemented across five diverse problems, showcasing the effectiveness of these techniques by utilizing step sizes of [Formula: see text] and [Formula: see text]. In order to gauge the accuracy of the methods, a comparison is drawn between the outcomes and the exact solutions, which are then presented in tabular and graphical format. The precision of these techniques is demonstrated through a detailed investigation and is found to be superior to the CBS, the Petrov–Galerkin Method (PGM) using Splines functions as basis functions and Septic B Splines functions as weight functions, the collocation method for ninth-order BVPs by Quintic B Splines and Sextic B Splines as evidenced by the comparison of AEs of CPS and CNPS with these alternative methods.
Berberine Metabolites Stimulate GLP-1 Secretion by Alleviating Oxidative Stress and Mitochondrial Dysfunction
Authors: Yang Wei-Li , Zhang Chen-Yang , Ji Wen-Yi , Zhao Li-Li , Yang Fang-Yuan , Zhang Lin , Cao Xi
Published: February 2024

Berberine (BBR) is a principal component of Rhizoma coptidis known for its therapeutic potential in treating diseases such as type 2 diabetes mellitus (T2DM) and obesity. Despite the trace levels of BBR in plasma, it’s believed that its metabolites play a pivotal role in its biological activities. While BBR is recognized to promote GLP-1 production in intestinal L cells, the cytoprotective effects of its metabolites on these cells are yet to be explored. The present study investigates the effects of BBR metabolites on GLP-1 secretion and the underlying mechanisms. Our results revealed that, out of six BBR metabolites, berberrubine (BBB) and palmatine (PMT) significantly increased the production and glucose-stimulated secretion of GLP-1 in GLUTag cells. Notably, both BBB and PMT could facilitate GLP-1 and insulin secretion and enhance glucose tolerance in standard mice. Moreover, a single dose of PMT could markedly increase plasma GLP-1 and improve glucose tolerance in mice with obesity induced by a high-fat diet. In palmitic acid or TNF[Formula: see text]-treated GLUTag cells, BBB and PMT alleviated cell death, oxidative stress, and mitochondrial dysfunction. Furthermore, they could effectively reverse inflammation-induced inhibition of the Akt signaling pathway. In general, these insights suggest that the beneficial effects of orally administered BBR on GLP-1 secretion are largely attributed to the pharmacological activity of BBB and PMT by their above cytoprotective effects on L cells, which provide important ideas for stimulating GLP-1 secretion and the treatment of T2DM.
CAPITAL FLOWS VOLATILITY AND SYSTEMIC RISK IN EMERGING MARKETS: A CASE OF TÜRKİYE
Authors: ALI SEYID AMJAD , MAHMUD SEYID FAHRİ , YÜLEK MURAT ALİ , AKOSMAN FATİH FURKAN
Published: February 2024

US sub-prime crisis in 2008–09 led the central banks undertake unconventional monetary policies. In turn, short-term and volatile capital flows into emerging markets surged significantly, reigniting an intense academic debate on the ability of the central banks in EMs to protect their financial markets from external shocks. This paper develops a partially integrated System Dynamics Model to simulate the impact of the capital flows on the dynamics of the nominal exchange rate in Türkiye. The results support the contention that several recent episodes of excessive depreciation of the Turkish Lira as well as the currency crisis of 2018 can be linked to the reversals of stocks of short-term FX liabilities. The model also integrates policy rate sub-module into the main model, allowing responses of the central bank to inflation and exchange rate as a feedback mechanism. The results of the module indicate that external factors may cause the central bank to loose monetary independence in order to maintain financial stability.
Gauge coupling unification in a minimal non-supersymmetric E6 GUT
Authors: Dash Chandini , Mishra Snigdha , Patra Sudhanwa , Sahu Purushottam
Published: February 2024

We consider a minimal renormalizable non-supersymmetric [Formula: see text] Grand Unified Theory using fundamental representation 27 for fermions and scalars. The scalar with adjoint representation 78 is also taken for direct breaking of [Formula: see text] to SM. The proposed model, guided by TeV-scale vector-like fermions and scalar leptoquark, offers successful gauge unification even in the absence of any intermediate symmetry. Embedded with threshold corrections, it is shown to be compatible with the present experimental limit on proton decay lifetime. The unique feature of the model shows that the GUT threshold corrections to the unification mass is controlled by superheavy gauge bosons only, thereby minimizing the uncertainty of the GUT predictions. The scalar leptoquark and vector-like fermions residing in 27 representation can explain flavor physics anomalies like [Formula: see text] as reported by the LHCb collaboration and the muon anomalous magnetic moment reported by the recent muon [Formula: see text] experiment at Fermilab. The model can also predict a sub-eV scale neutrino at one-loop level via exchange of W and Z gauge bosons through MRIS mechanism.
A Method of Reliability Assessment Based on Trend Analysis for Open Source Software
Authors: Miyamoto Shoichiro , Tamura Yoshinobu , Yamada Shigeru
Published: February 2024

Software reliability growth model (SRGM) is used as one of the reliability assessment methods to assess the software reliability. In SRGM, the degree of reliability growth may fluctuate greatly according to change in the internal state of the software. It is called the change point (CP). Several researchers proposed the SRGM considering CP. In the open source software (OSS), there are many projects that continue development even after the software is released. Therefore, major updates with breaking changes may occur in it. The major updates can be a factor that causes a CP because it greatly changes the internal state of the OSS. This paper focuses on the relationship between CP and software updates. We collect OSS fault data from a bug tracking system. Moreover, we examine the behavior of SRGM before and after software updates. Furthermore, we discuss the applicability of SRGM for CP in OSS. Also, we compare the proposed model based on CP with the model without CP. As a result, we have confirmed that the SRGM can evaluate the reliability in the environment with major updates. Moreover, the proposed method performs better than without considering CP model. Especially, the exponential model’s mean value function is the suitable method to assess the OSS reliability for the proposed method.