bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel isolates of hydrogen-oxidizing chemolithoautotrophic
Sulfurospirillum
provide insight to the functions and adaptation mechanisms of Campylobacteria in shallow-water hydrothermal vents
Authors: Wang Li , Cheng Xinyi , Guo Yizhe , Cao Junwei , Sun Mingye , Hwang Jiang-Shiou , Liu Rulong , Fang Jiasong
Published: August 2024

Enhancing the availability of representative isolates from hydrothermal vents (HTVs) is imperative for comprehending the microbial processes that propel the vent ecosystem. In recent years, Campylobacteria have emerged as the predominant and ubiquitous taxon across both shallow and deep-sea vent systems. Nevertheless, only a few isolates have been cultured, primarily originating from deep-sea HTVs. Presently, no cultivable isolates of Campylobacteria are accessible in shallow water vent systems (<200 m), which exhibit markedly distinct environmental conditions from their deep-sea counterparts. In this study, we enriched a novel isolate (genus
Sulfurospirillum
, Campylobacteria) from shallow-water HTVs of Kueishan Island. Genomic and physiological analysis revealed that this novel Campylobacteria species grows on a variety of substrate and carbon/energy sources. The pan-genome and phenotypic comparisons with 12 previously isolated
Sulfurospirillum
species from different environments supported the identification of functional features in
Sulfurospirillum
genomes crucial for adaptation to vent environments, such as sulfur oxidation, carbon fixation, biofilm formation, and benzoate/toluene degradation, as well as diverse genes related with signal transportation. To conclude, the metabolic characteristics of this novel Campylobacteria augment our understanding of Campylobacteria spanning from deep-sea to shallow-water vent systems.

IMPORTANCE

Campylobacteria emerge as the dominant and ubiquitous taxa within vent systems, playing important roles in the vent ecosystems. However, isolated representatives of Campylobacteria have been mainly from the deep-sea hydrothermal fields, leaving a significant knowledge gap regarding the functions, activities, and adaptation strategies of the vent microorganisms in shallow-water hydrothermal vents (HTVs). This study bridges this gap by providing insights into the phenomics and genomic diversity of genus
Sulfurospirillum
(order Campylobacterales, class Campylobacteria) based on data derived from a novel isolate obtained from shallow-water HTVs. Our mesophilic isolate of
Sulfurospirillum
not only augments the genus diversity of Campylobacteria pure cultures derived from vent systems but also serves as the inaugural reference isolate for Campylobacteria in shallow-water environments.
Antibacterial effect of phage cocktails and phage-antibiotic synergy against pathogenic
Klebsiella pneumoniae
Authors: zhao Mengshi , Li Hongru , Gan Dehao , Wang Mengzhu , Deng Hui , Yang Qiu E.
Published: August 2024

The global rise of antibiotic resistance has renewed interest in phage therapy, as an alternative to antibiotics to eliminate multidrug-resistant (MDR) bacterial pathogens. However, optimizing the broad-spectrum efficacy of phage therapy remains a challenge. In this study, we addressed this issue by employing strategies to improve antimicrobial efficacy of phage therapy against MDR
Klebsiella pneumoniae
strains, which are notorious for their resistance to conventional antibiotics. This includes the selection of broad host range phages, optimization of phage formulation, and combinations with last-resort antibiotics. Our findings unveil that having a broad host range was a dominant trait of isolated phages, and increasing phage numbers in combination with antibiotics significantly enhanced the suppression of bacterial growth. The decreased incidence of bacterial infection was explained by a reduction in pathogen density and emergence of bacterial resistance. Furthermore, phage-antibiotic synergy (PAS) demonstrated considerable broad-spectrum antibacterial potential against different clades of clinical MDR
K. pneumoniae
pathogens. The improved treatment outcomes of optimized PAS were also evident in a murine model, where mice receiving optimized PAS therapy demonstrated a reduced bacterial burden in mouse tissues. Taken together, these findings offer an important development in optimizing PAS therapy and its efficacy in the elimination of MDR
K. pneumoniae
pathogens.

IMPORTANCE

The worldwide spread of antimicrobial resistance (AMR) has posed a great challenge to global public health. Phage therapy has become a promising alternative against difficult-to-treat pathogens. One important goal of this study was to optimize the therapeutic efficiency of phage-antibiotic combinations, known as phage-antibiotic synergy (PAS). Through comprehensive analysis of the phenotypic and genotypic characteristics of a large number of CRKp-specific phages, we developed a systematic model for phage cocktail combinations. Crucially, our finding demonstrated that PAS treatments not only enhance the bactericidal effects of colistin and tigecycline against multidrug-resistant (MDR)
K. pneumoniae
strains in
in vitro
and
in vivo
context but also provide a robust response when antibiotics fail. Overall, the optimized PAS therapy demonstrates considerable potential in combating diverse
K. pneumoniae
pathogens, highlighting its relevance as a strategy to mitigate antibiotic resistance threats effectively.
Challenges and innovations in managing a complex giant bilateral juvenile nasopharyngeal angiofibroma with intracranial extension
Authors: Eugine Reshma , PS Suji , Bhardwaj Abhishek , Sahu Madhu Priya
Published: August 2024

Juvenile nasopharyngeal angiofibroma (JNA) is a highly vascular, benign and locally aggressive tumour that predominantly affects adolescent males. Recognised for its persistence and propensity to recur, patients usually present with gradual development of symptoms such as epistaxis and nasal obstruction over several months to years. Diagnosis typically combines clinical assessments and radiographic studies, often involving preoperative angiography to identify feeder vessels and facilitate embolisation, reducing intraoperative bleeding during surgical interventions. A comprehensive approach to treatment, considering both tumour characteristics and patient well-being, is crucial, particularly when dealing with cases involving intracranial extension. Surgical excision remains the primary treatment for angiofibroma, though radiotherapy is considered for cases with intracranial extension. This case report outlines a case involving a young man in his 20s with a large bilateral JNA extending into the intracranial area. The patient underwent preoperative embolisation followed by surgical resection using a nasofrontomaxillary swing approach with a bifrontal craniotomy window. This alternative approach provided enhanced exposure to address the involvement of the infratemporal fossa, anterior and middle skull base. Postoperatively, residual intracranial tumour was managed with radiation therapy. Over a 2-year follow-up, the patient remains asymptomatic, with a minor postradiation reduction in the intracranial component’s size.
HIV-1 subtype-specific drug resistance on dolutegravir-based antiretroviral therapy: protocol for a multicentre study (DTG RESIST)
Authors: Egger Matthias , Sauermann Mamatha , Loosli Tom , Hossmann Stefanie , Riedo Selma , Beerenwinkel Niko , Jaquet Antoine , Minga Albert , Ross Jeremy , Giandhari Jennifer , Kouyos Roger D , Lessells Richard
Published: August 2024

Introduction

HIV drug resistance poses a challenge to the United Nation’s goal of ending the HIV/AIDS epidemic. The integrase strand transfer inhibitor (InSTI) dolutegravir, which has a higher resistance barrier, was endorsed by the WHO in 2019 for first-line, second-line and third-line antiretroviral therapy (ART). This multiplicity of roles of dolutegravir in ART may facilitate the emergence of dolutegravir resistance.

Methods and analysis

Nested within the International epidemiology Databases to Evaluate AIDS (IeDEA), DTG RESIST is a multicentre study of adults and adolescents living with HIV in sub-Saharan Africa, Asia, and South and Central America who experienced virological failure on dolutegravir-based ART. At the time of virological failure, whole blood will be collected and processed to prepare plasma or dried blood spots. Laboratories in Durban, Mexico City and Bangkok will perform genotyping. Analyses will focus on (1) individuals who experienced virological failure on dolutegravir and (2) those who started or switched to such a regimen and were at risk of virological failure. For population (1), the outcome will be any InSTI drug resistance mutations, and for population (2) virological failure is defined as a viral load >1000 copies/mL. Phenotypic testing will focus on non-B subtype viruses with major InSTI resistance mutations. Bayesian evolutionary models will explore and predict treatment failure genotypes. The study will have intermediate statistical power to detect differences in resistance mutation prevalence between major HIV-1 subtypes; ample power to identify risk factors for virological failure and limited power for analysing factors associated with individual InSTI drug resistance mutations.

Ethics and dissemination

The research protocol was approved by the Biomedical Research Ethics Committee at the University of KwaZulu-Natal, South Africa and the Ethics Committee of the Canton of Bern, Switzerland. All sites participate in International epidemiology Databases to Evaluate AIDS and have obtained ethics approval from their local ethics committee to collect additional data.

Trial registration number

NCT06285110.
Clinic of Hope: bridging infectious disease and orthopaedic surgery in prosthetic joint infection management
Authors: Wu Kevin A , Seidelman Jessica L , Gettler Erin B , Hendershot Edward F , Jiranek William A , Seyler Thorsten M
Published: August 2024

Prosthetic joint infections (PJIs) following total joint arthroplasty are a significant and costly complication. To address fragmented care typically seen with separate management, we established a combined infectious disease and orthopaedic surgery clinic at Duke Health in July 2020. This clinic focuses on patients experiencing acute deterioration or multiple PJI episodes, often at the stage where amputation is the only option offered. From July 2021 to March 2024, the clinic completed 974 visits with 319 unique patients. The clinic maintained a low no-show rate of 5.0%. Treatment plans included procedures such as debridement, antibiotics and implant retention (38%), as well as implant explantation and one-stage exchange (32% each), with amputation required in only 4% of cases. The integrated clinic model facilitated real-time, multidisciplinary care, improving patient outcomes and operational efficiency. This approach offers a promising model for managing complex infections.
Equity in Choosing Wisely and beyond: the effect of health literacy on healthcare decision-making and methods to support conversations about overuse
Authors: Muscat Danielle M , Cvejic Erin , Smith Jenna , Thompson Rachel , Chang Edward , Tracy Marguerite , Zadro Joshua , Linder Robyn , McCaffery Kirsten
Published: August 2024

Objective

To (a) examine whether the effect of the Choosing Wisely consumer questions on question-asking and shared decision-making (SDM) outcomes differs based on individuals’ health literacy and (b) explore the relationship between health literacy, question-asking and other decision-making outcomes in the context of low value care.

Methods

Preplanned analysis of randomised trial data comparing: the Choosing Wisely questions, a SDM video, both interventions or control (no intervention). Randomisation was stratified by participant health literacy (‘adequate’ vs ‘limited’), as assessed by the Newest Vital Sign.

Main outcome measures

Self-efficacy to ask questions and be involved in decision-making, and intention to engage in SDM.

Participants

1439 Australian adults, recruited online.

Results

The effects of the Choosing Wisely questions and SDM video did not differ based on participants’ health literacy for most primary or secondary outcomes (all two-way and three-way interactions p>0.05). Compared with individuals with ‘adequate’ health literacy, those with ‘limited’ health literacy had lower knowledge of SDM rights (82.1% vs 89.0%; 95% CI: 3.9% to 9.8%, p<0.001) and less positive attitudes towards SDM (48.3% vs 58.1%; 95% CI: 4.7% to 15.0%, p=0.0002). They were also more likely to indicate they would follow low-value treatment plans without further questioning (7.46/10 vs 6.94/10; 95% CI: 0.33 to 0.72, p<0.001) and generated fewer questions to ask a healthcare provider which aligned with the Choosing Wisely questions (χ2(1)=73.79, p<.001). On average, 67.7% of participants with ‘limited’ health literacy indicated that they would use video interventions again compared with 55.7% of individuals with ‘adequate’ health literacy.

Conclusion

Adults with limited health literacy continue to have lower scores on decision-making outcomes in the context of low value care. Ongoing work is needed to develop and test different intervention formats that support people with lower health literacy to engage in question asking and SDM.
Long-term risk of heart failure in adult cancer survivors: a systematic review and meta-analysis
Authors: Wong Joshua , Soh Cheng Hwee , Wang Benjamen , Marwick Thomas
Published: August 2024

Background

Cancer survivors are at increased risk of heart failure (HF). While cardiotoxicity is commonly sought at the time of cancer chemotherapy, HF develops as a result of multiple ‘hits’ over time, and there is limited evidence regarding the frequency and causes of HF during survivorship.

Objectives

This systematic review sought to investigate the relationship between cardiotoxic cancer therapies and HF during survivorship.

Methods

We searched the EMBASE, MEDLINE and CINAHL databases for studies reporting HF in adult survivors (≥50 years old), who were ≥5 years postpotential cardiotoxic cancer therapy. A random effects model was used to examine the associations of HF.

Results

Thirteen papers were included, comprising 190 259 participants (mean age 53.5 years, 93% women). The risk of HF was increased (overall RR 1.47 (95% CI (1.17 to 1.86)). Cardiotoxic treatment, compared with cancer alone, provided a similar risk (RR of 1.46 (95% CI 0.98 to 2.16)). The overall HF incidence rate was 2.1% compared with 1.7% in the control arm—an absolute risk difference of 0.4%. In the breast cancer population ratio (11 studies), the overall HF RR was 2.57 (95% CI 1.35 to 4.90)). Although heterogeneity was significant (I2=77.2), this was explained by differences in patient characteristics; once multivariable analysis accounted for follow-up duration (OR 0.99, 95% CI (0.97 to 0.99), p=0.047), age (OR 1.14, 95% CI (1.04 to 1.25), p=0.003) and hypertension (OR 0.95, 95% CI (0.92 to 0.98), p<0.001), residual heterogeneity was low (I2=28.7).

Conclusions

HF is increased in adult cancer survivors, associated with cardiotoxic cancer therapy and standard risk factors. However, the small absolute risk difference between survivors and controls suggests that universal screening of survivors is unjustifiable. A risk model based on age, cardiotoxic cancer therapy and standard risk factors may facilitate a selective screening process in this at-risk population.
TargetingGsk3areverses immune evasion to enhance immunotherapy in hepatocellular carcinoma
Authors: Zheng Xin , Yang Luyu , Shen Xiaotian , Pan Junjie , Chen Yiran , Chen Jixuan , Wang Hao , Meng Jiaqi , Chen Zhenchao , Xie Sunzhe , Li Yitong , Zhu Bolun , Zhu Wenwei , Qin Lunxiu , Lu Lu
Published: August 2024

Background

Immune escape is an important feature of hepatocellular carcinoma (HCC). The overall response rate of immune checkpoint inhibitors (ICIs) in HCC is still limited. Revealing the immune regulation mechanisms and finding new immune targets are expected to further improve the efficacy of immunotherapy. Our study aims to use CRISPR screening mice models to identify potential targets that play a critical role in HCC immune evasion and further explore their value in improving immunotherapy.

Methods

We performed CRISPR screening in two mice models with different immune backgrounds (C57BL/6 and NPG mice) and identified the immunosuppressive geneGsk3aas a candidate for further investigation. Flow cytometry was used to analyze the impact ofGsk3aon immune cell infiltration and T-cell function. RNA sequencing was used to identify the changes in neutrophil gene expression induced byGsk3aand alterations in downstream molecules. The therapeutic value of the combination ofGsk3ainhibitors and anti-programmed cell death protein-1 (PD-1) antibody was also explored.

Results

Gsk3a, as an immune inhibitory target, significantly promoted tumor growth in immunocompetent mice rather than immune-deficient mice.Gsk3ainhibited cytotoxic T lymphocytes (CTLs) function by inducing neutrophil chemotaxis.Gsk3apromoted self-chemotaxis of neutrophil expression profiles and neutrophil extracellular traps (NETs) formation to block T-cell activity through leucine-rich α-2-glycoprotein 1 (LRG1). A significant synergistic effect was observed whenGsk3ainhibitor was in combination with anti-PD-1 antibody.

Conclusions

We identified a potential HCC immune evasion target,Gsk3a, through CRISPR screening.Gsk3ainduces neutrophil recruitment and NETs formation through the intermediate molecule LRG1, leading to the inhibition of CTLs function. TargetingGsk3acan enhance CTLs function and improve the efficacy of ICIs.
Trauma advanced practice provider education: the current state of trauma advanced practice provider postgraduate education in the United States
Authors: Lasinski Alaina M , Shaughnessy Allysen , Claridge Jeffrey A
Published: August 2024

Background

Postgraduate education for advanced practice providers (APPs) is a rapidly evolving field and includes residencies and fellowships designed to help narrow the gap between physicians and APPs. The current state of trauma APP postgraduate programs in the U.S. is unknown. The aim of this study is to identify the APP postgraduate programs in the U.S. dedicated to trauma training and to understand the baseline characteristics of these programs and their curriculums, including which technical skills and bedside procedures a trauma APP should be expected to perform.

Methods

This is a cross-sectional study of all identifiable APP postgraduate programs in trauma surgery in the U.S. through June 2022. A survey tool designed to better understand training programs and curriculums was created. A web-based survey using Qualtrics was sent to the program directors of the identifiable trauma programs. Descriptive statistics were calculated as appropriate.

Results

Eight programs were identified as primarily trauma training programs. Six programs completed the entire survey, and one program completed 50% of the survey. Programs vary in the number of graduates, clinical rotations, and educational curriculums, though all programs offer didactics and simulation curriculums for procedure skill development. Most programs are not accredited.

Conclusion

This is the first study developed to understand the content and curriculums of postgraduate trauma programs for APPs. There are only a handful of programs dedicated to trauma training, and their educational offerings are diverse, with similarities across programs in expected procedural competency. There is a need for trauma programs to invest in and further standardize APP training.

Level of evidence

IV.
AAC Dutton Canada Western Red Spring wheat
Authors: Kumar S. , Nilsen K.T. , Green D. , McCallum B. , Fetch T. , Menzies J. , Aboukhaddour R. , Henriquez M.-A.
Published: August 2024

AAC Dutton (BW1094) is a hollow-stemmed, awned, and high yielding Canada Western Red Spring (CWRS) wheat cultivar suited to the growing conditions of Western Canada. AAC Dutton was 1% higher yielding than AAC Viewfield, the highest yielding check in the Central Bread Wheat Cooperative registration trials (2019–2021). Within the same test, AAC Dutton was 10% higher yielding than Carberry. AAC Dutton matured 1 day earlier than Glenn, Carberry, and AAC Viewfield and less than a day later than Unity: Unity being the earliest maturing check in the registration trial. AAC Dutton was 10 cm shorter than Unity with lodging score lower than the mean of the checks. The test weight of AAC Dutton was similar to Unity while the 1000-kernel weight was higher than AAC Viewfield. The grain protein content of AAC Dutton was lower than all the checks. AAC Dutton had a moderately resistant reaction to Fusarium head blight ( Fusarium graminearum Schwabe) and stripe rust ( Puccinia striiformis Westend). AAC Dutton had optimal resistance to leaf rust ( Puccinia triticina Erikss.), stem rust ( Puccinia graminis Pers. f. sp. tritici Eriks. & E. Henn), common bunt ( Tilletia caries [DC] Tul. & C. Tul.), and to orange blossom wheat midge ( Sitodiplosis mosellana Géhin). AAC Dutton was registered under the CWRS class.
Multiple soil health indicators are responsive to summer cover crops on an irrigated organic farm
Authors: Larney Francis J. , Lupwayi Newton Z. , Forge Thomas A. , Catton Haley A. , Geddes Charles M. , Chau Henry Wai , Lemke Reynald L. , Helgason Bobbi L.
Published: August 2024

While cover crops (CC) are known to enhance soil health, outcomes are often subtle and confined to a shallow surface soil layer. We assessed 15 soil health indicators over three CC trials with a 15-species Blend polyculture, a Mustard biculture (white ( Sinapsis alba L.) and brown ( Brassica juncea (L.) Czern.) mustards), Buckwheat ( Fagopyrum esculentum Moench), and Faba bean ( Vicia faba L.) monocultures, and a Weedy fallow (no CC, weeds allowed to grow) on an organic farm in southern Alberta. Soil sampling times included (i) summer pretermination; (ii) fall post-termination; and (iii) spring post-termination of CC. Twelve of 15 soil health indicators showed significant effects of CC treatment for at least one sampling time. Soil organic C (SOC) ranked highest with 80% of sampling times showing significant CC effects. N-related indicators (total N (TN), nitrate-N)) were also quite sensitive, being significantly affected by CC treatment at 60% of sampling times. Three soil health indicators (acid phosphomonoesterase (AcP), wet aggregate stability, and free-living nematodes (FLN)) were consistent in their nonresponses to CC treatment at all sampling times. Comparing CC treatments with a Weedy fallow, showed that not all enhancements of soil health were explained by inclusion of a CC, with Weedy fallow as effective for some indicators. A polyculture Blend significantly enhanced soil health over a monoculture CC or Weedy fallow in 46% of instances of soil health indicator improvement. While CC led to enhancement of soil health, results were not always consistent, being contingent on specific indicators.
Distinguishing signature of Kerr-MOG black hole and superspinar via Lense–Thirring precession
Authors: Pradhan Parthapratim
Published: August 2024

We examine the geometrical differences between the black hole (BH) and naked singularity (NS) or superspinar via Lense–Thirring (LT) precession in spinning modified-gravity (MOG). For BH case, we show that the LT precession frequency ($$\Omega _{LT}$$

Ω

LT

) along the pole is proportional to the angular-momentum (J) parameter or spin parameter (a) and is inversely proportional to the cubic value of radial distance parameter, and also governed by Eq. (1). Along the equatorial plane it is governed by Eq. (2). While for superspinar, we show that the LT precession frequency is inversely proportional to the cubic value of the spin parameter and it decreases with distance by MOG parameter as derived in Eq. (3) at the pole and in the limit $$a>>r$$

a
>
>
r

(where a is spin parameter). For $$\theta \ne \frac{\pi }{2}$$

θ
≠

π
2

and in the superspinar limit, the spin frequency varies as $$\Omega _{LT}\propto \frac{1}{a^3\cos ^4\theta }$$

Ω

LT

∝

1

a
3

cos
4

θ

and by Eq. (38).
Effect of Helium Plasma Irradiation on Microstructures and Mechanical Properties of Tungsten
Authors: Kengesbekov Aidar , Rakhadilov Bauyrzhan , Satbaeva Zarina , Kambarov Yedilzhan
Published: August 2024

The paper presents the results of the study of tungsten surface structure modification under helium plasma irradiation. It is revealed that during irradiation of samples, surface modification in the form of relief development as a result of irradiation is observed. X‐ray phase analysis showed that no new phases of the W system were found after irradiation, only an increase in the intensity of diffraction lines was observed. There are significant differences in the microstructure of tungsten depending on the temperature of helium plasma irradiation in the above range. It is assumed that the cause of defects is the extremely low solubility of helium in tungsten. Metallographic analysis has shown that at irradiation of tungsten samples in time modes 1 and 1.5 hours, the degree of relief development is not high in comparison with the tungsten sample irradiated in the 0.5‐hour mode. The greatest increase in surface roughness of the sample irradiated for 1 hour was registered, which is associated with the formation of small cracks, bubbles, and pores in the surface layer. At the same time, in the samples irradiated for 1.5 hours, the surface of which is characterized by chaotically located protrusions and depressions of various shapes, the roughness parameter Ra was 0.0603 μm. It was found that at temperature regimes T = 1200°C and T = 1500°C, the microhardness of tungsten increases by 10% and 11%, respectively.
Tenecteplase Catheter‐Directed Thrombolytic Therapy in Submassive Pulmonary Embolism: A Case Report
Authors: Ghaziri Dania , Bou Fakhreddine Hisham , Sawaya Fadi , Jaber Farah , Bou Akl Imad
Published: August 2024

Introduction: In pulmonary embolism (PE), when used for catheter‐directed thrombolysis (CDT), low‐dose alteplase is associated with good outcomes. Tenecteplase has been only used as intravenous for this indication. In the context of our national economic crisis where alteplase was unavailable, we describe our experience with tenecteplase CDT.

Case: A 73‐year‐old male, hypertensive and smoker with COPD, presented to the ED with intermediate high‐risk PE.(ED) with intermediate high‐risk PE. Heparin infusion was initiated. A few hours later, the patient developed atrial fibrillation (AF) for which amiodarone infusion was started. Also, a left femoral and popliteal vein thrombosis was also confirmed by the lower extremity duplex. As the patient remained dyspneic with unstable vital signs, the decision was to perform a CDT. In the absence of alteplase, tenecteplase was used at 0.5 mg/h over 30 h, for a total of 15 mg.

Result: Twenty‐four hours after tenecteplase initiation, dyspnea and vital signs had significantly improved. Oxygen support was gradually dropping to finally stop. Being on concomitant heparin infusion, the patient had a mild blood oozing at the femoral vein site of entry; however, this did not require any transfusion or discontinuation of heparin. The patient regained his baseline physical and mental functions and was discharged on enoxaparin and amiodarone tablet.

Discussion: This is the first experience describing the use of tenecteplase as part of CDT in a patient with acute intermediate high‐risk PE. The combination to therapeutic heparin infusion, already described in different clinical scenarios with intravenous tenecteplase, was safe and well tolerated

Conclusion: CDT with tenecteplase was, for the first time, safely and effectively used in an intermediate high‐risk PE patient. However, more studies are needed to confirm and establish these findings.
Nutritional Quality Differences of Pleurotus sajor-caju M2145 and Pleurotus ostreatus M2191 in Mixed Substrates of Brewer’s Spent Grain Supplemented with Lignocellulosic Residues
Authors: Gebeyehu Demissew , Tesfaw Asmamaw
Published: August 2024

Oyster mushrooms are a type of lignocellulolytic fungus that is used for both culinary and medicinal purposes. The purpose of this study was to assess the nutritional value, biological efficiency, and yields of P. ostreatus M2191 and P. sajor-caju M2145 grown on spent grain from breweries that have been supplemented with various agricultural wastes. The primary substrates at varying compositions included sawdust, wheat straw, cottonseed, teff straw, bean straw, and brewer’s spent grain. Two percent gypsum and eight percent wheat bran were added as supplements to the primary substrates. A daily assessment of the growth and development of the Pleurotus species was conducted during their aseptic cultivation. A combination of 25% brewer’s spent grain and 75% cottonseed produced the highest biological efficiency and nutritional attributes. The lowest nutritional compositions, yields, and biological efficiency were found when eucalyptus sawdust was used alone or in combination with other agroindustrial residues. Under the weather conditions of Debre Berhan, P. ostreatus M2191 and P. sajor-caju M2145 could be grown using agricultural residues and leftover grains from the brewery.
The Relationship between Stress and Preclinical Dental Students’ Performance: A Longitudinal Study
Authors: Lugassy Diva , Ben-Izhack Gil , Zissu Sara , Shitrit Lahav Rotem , Rosner Ophir , Uziel Nir , Naishlos Sarit , Shely Asaf
Published: August 2024

Background. The aim of this study was to evaluate the changing levels of stress among dental students during 8 months of a basic manual skills course in the preclinical year and to examine the association between stress and dental performance. Methods. A longitudinal study was conducted in the 2023 academic year in a total of 58 (male = 17 and female = 41; mean age = 26.43, range 22–33) undergraduate dental students at Tel Aviv University of dentistry during their fourth year of study. Depression Anxiety Stress Scale (DASS‐21) and Dental Environment Stress (DES) questionnaires were used to assess the psychological well‐being and the severity of DASS symptoms experienced by the students. The students’ dental performances were assessed using two manual tests on plastic teeth. The questionnaires and the manual tests were used at three periods of time, T0, T1, and T2. Wilcoxon signed‐rank tests were performed to compare the DASS scores and DES stressors of dental students between T0, T1, and T2. Kendall’s nonparametric correlations were calculated to investigate the relationships of DES stressors and depression, anxiety, and stress scores with manual performance. Conclusions. The perception of high stress by dental students is due to the stressful education process of the preclinical year. There is an inverse correlation between the lower level of anxiety and the increase level of dental performance with 74% of the variance in dental performance explained by the anxiety score. Work‐related stressors such as manual skills might reduce dental performance in contrast to non‐work‐related factors such as financial obligations, personal issues, and family factors, which might increase student dental performance.
Analysis of Ex‐Vessel Debris Coolability of Boiling Water Reactors
Authors: Matsumoto Toshinori , Hibiki Takashi , Maruyama Yu
Published: August 2024

To evaluate the effectiveness of the wet cavity strategy, the authors developed a stochastic evaluation method that considers the uncertainties of the molten material conditions ejected from reactor pressure vessels. This study analyzed the probability of ex‐vessel debris coolability under the wet cavity strategy. The first step was uncertainty analysis using the severe accident analysis code MELCOR to obtain the melt condition. Five uncertainty parameters related to the core degradation and transfer process were chosen. With the assumed probabilistic distributions, the input parameter sets were generated using the Latin hypercube sampling (LHS) method. Analyses were conducted, and the conditions of the melt were obtained. The second step was to analyze the melt behavior in the water and the spreading radius using the JASMINE code and to calculate the height of the debris on the floor. The probabilistic distribution of parameters for the JASMINE analyses was determined from the MELCOR analysis results. LHS generated 200 parameter sets. The depths of the water pool in the analysis were 0.5, 1.0, and 2.0 m. The debris height was compared with the criterion to judge its coolability. Consequently, the probability of successful debris cooling was obtained through the sequence of calculations. The feasibility and technical difficulties in the MELCOR‐JASMINE combined analysis were also discussed.
Prevalence of Helminth Infections in Patients with Celiac Disease
Authors: Magen Eli , Merzon Eugene , Vinker Shuster Michal , Green Ilan , Magen Israel , Golan-Cohen Avivit , Israel Ariel
Published: August 2024

Introduction: The aim of this study was to investigate the association between helminth infections and celiac disease (CeD), examining various demographic and clinical factors in CeD cases compared to controls. Methods: We conducted a retrospective case-control study utilizing Leumit Health Care Services’ electronic health records. The study encompassed individuals with CeD and a matched control group. We analyzed demographic and clinical characteristics, examining their association with helminth infections. Results: We observed CeD cases and controls had similar mean ages (17.8 years vs. 18.0 years, p = 0.565) and gender distributions (64.0% females in both groups, p = 0.999). There were no significant differences in socioeconomic status and ethnic distribution between the two groups. Most of the helminthiases in the CeD group were due to intestinal helminthiases, and most of the intestinal helminthiases were nematode (roundworm) infections. Enterobiasis (the pinworm Enterobius vermicularis) is involved in most cases (odds ratio 1.32, 95% confidence interval 1.20–1.45, p < 0.001). While the prevalence of ascariasis and anisakiasis was also higher in the CeD group, these differences were not statistically significant (p = 0.115 and p = 0.174, respectively). No significant differences were found in the prevalence of other specific helminth infections, such as echinococcosis, cestode infections, and strongyloidiasis. Conclusions: This study reveals an unexpected association between CeD and helminth infections, challenging prevailing hypotheses, particularly within the context of the hygiene hypothesis. These findings warrant further investigation to elucidate the mechanisms underlying this intriguing relationship.
Disembodiment and Affective Resonances in Esketamine Treatment of Depersonalized Depression Subtype: Two Case Studies
Authors: Sarasso Pietro , Billeci Martina , Ronga Irene , Raffone Fabiola , Martiadis Vassilis , Di Petta Gilberto
Published: August 2024

Introduction: Dissociative experiences are considered undesirable ketamine’s adverse events. However, they might be crucial for ketamine’s antidepressant effects, at least in some depression subtypes. Current understandings of ketamine’s therapeutic potentials converge on the so-called “relaxed prior hypothesis,” suggesting that glutamatergic blockage up-weights bottom-up surprising somatosensory/affective states. As a result, ketamine improves short-term plasticity in depression by enhancing sensitivity to interoceptive signals. Methods: We selected 2 case studies for their paradigmatic description of “depersonalized depression” (Entfremdungsdepression) symptoms. Patients were included in a 6-month-long esketamine program for treatment resistant depression, during which we collected their spontaneous experience with esketamine. According to a neurophenomenological approach, we combined subjective reports from unstructured clinical interviews and the review of previous objective neuroimaging results and neurocomputational models to unveil the relation between esketamine antidepressant effects and interoceptive sensitivity. Results: According to our clinical observations, esketamine-induced dissociation might be particularly effective in the depersonalized depression subtype, in which interoceptive awareness and interaffectivity are particularly compromised. Ketamine and esketamine’s dissociative effects and particularly disembodiment might suspend previously acquired patterns of feeling, sensing, and behaving. Conclusions: Coherently with previous research, we suggest that esketamine-induced disembodiment allows for a transient window of psychological plasticity and enhanced sensitivity, where the body recovers its permeability to affective affordances.
Efficacy of Beclomethasone Dipropionate in Lowering Fecal Calprotectin Levels in Patients with Ulcerative Colitis in Clinical Remission and at Risk of Relapse: The Becalcu Randomized, Controlled Trial
Authors: Ginard Daniel , Barreiro-de Acosta Manuel , Nos Pilar , Moraleja Irene , Muñoz Nuñez Fernando , Aldeguer Xavier , Echarri Ana , Villoria Albert , Riestra Sabino , Boscá Watts Marta Maia , González-Lama Yago , Royo Vanesa , Ferreiro-Iglesias Rocío , Iborra Marisa , Elorza Ainara , Fernandez-Pordomingo Alejandra , Sans Miquel ,   On behalf of the Becalcu study
Published: August 2024

Introduction: Identifying novel treatment strategies for patients with ulcerative colitis (UC) and at risk of relapse is critical. The objective of this study was to assess the efficacy of beclomethasone dipropionate (BDP) in lowering fecal calprotectin (FC) levels in UC patients in clinical remission and at risk of relapse. Methods: This multicenter study comprised a double-blind, randomized, placebo-controlled phase (part I) and an open-label, non-randomized phase (part II). Eligible participants with UC in clinical remission treated with 5-aminosalicylic acid and with FC levels ≥250 μg/g were randomized to receive 5 mg/day of BDP or placebo for 4 weeks (part I). At week 5, patients with FC ≥100 μg/g were treated with 5 mg/day of BDP for 4 weeks (part II), and FC levels were tested at week 9. Results: Forty-three patients were randomized: 22 received BDP (group A) and 21 placebo (group B). At week 4, 13 patients (59.1%) in group A and 3 (17.6%) in group B had FC levels <100 μg/g (p value = 0.010). In the double-blind phase of the study, no patient relapsed in group A and 4 in group B (p value = 0.049). Both treatment groups showed a favorable safety profile, with the most common adverse events being gastrointestinal disorders. Conclusion: In this multicenter, randomized clinical trial including patients with UC in clinical remission but with elevated FC, BDP was efficacious in reducing FC and well-tolerated.
Validation of self-reported measures of nutritional status: a study based on the PNS 2019
Authors: Brito Renatha Celiana da Silva , Oliveira Angelo Giuseppe Roncalli da Costa
Published: August 2024

OBJETIVO: Analisar a validade da autorreferência de medidas antropométricas (peso e altura) para a classificação do estado nutricional de adultos e idosos brasileiros a partir dos dados da Pesquisa Nacional de Saúde (PNS), edição de 2019. MÉTODOS: A amostra da PNS é constituída por domicílios particulares permanentes de todas as unidades federativas do Brasil e este é um recorte transversal no qual foram identificados 6.571 registros com dados aferidos e referidos, não sendo identificados dados perdidos para uma variável quando na presença de outra. A validação foi realizada com 6.381 dados após a retirada de dados atípicos. As variáveis utilizadas para estratificação foram: sexo, idade, raça/cor, escolaridade e renda e, para analisar a concordância entre as categorias do estado nutricional, foram utilizados o Coeficiente Kappa ponderado e o Coeficiente de Correlação Intraclasse (CCI). A acurácia foi analisada com base nos valores de sensibilidade, especificidade, valor preditivo positivo (VPP) e valor preditivo negativo (VPN). E para a validade de constructo, foi realizada uma regressão de Poisson para cada desfecho (aferido e autorreferido), com as variáveis independentes “sexo”, “cor/raça”, “escolaridade” e “renda familiar”. RESULTADOS: Todas as análises mostraram resultados positivos para a validação. Houve uma maior reprodutibilidade entre adultos (18 a 59 anos) quando comparados às pessoas idosas e entre homens quando comparados às mulheres. CONCLUSÃO: Esta validação indica uma possibilidade concreta de realizar estudos observacionais de associação tendo como variável de desfecho o estado nutricional referido, como uma estratégia eficiente, podendo minimizar as dificuldades operacionais frequentemente encontradas.
High-Dimensional Single-Cell Mass Cytometry Demonstrates Differential Platelet Functional Phenotypes in Infants With Congenital Heart Disease
Authors: Gu Sean X. , Marcus Brian S. , Gu Vivian W. , Varghese Adarsh P. , Hwa John , Faustino E. Vincent S.
Published: August 2024

BACKGROUND:

Congenital heart disease (CHD) is a group of complex heart defects associated with hematologic abnormalities, including increased risk of thrombotic and bleeding events. Past studies have observed evidence of platelet hyperreactivity, while other studies showed decreased platelet activation in patients with CHD. The goal of this study was to develop a mass spectrometry approach to characterize single platelets in infants with CHD and identify potential etiology for such discrepant results.

METHODS:

We enrolled 19 infants with CHD along with 21 non-CHD controls at Yale New Haven Children’s Heart Center. A single-cell high-dimensional mass cytometry method was developed to quantitatively interrogate platelet surface markers in whole blood. Additionally, plasma cytokine analysis was performed through a multiplexed panel of 52 vascular and inflammatory markers to assess for platelet releasates.

RESULTS:

We found that infants with CHD had significant differences in platelet activation and functional markers by mass cytometry compared with non-CHD controls. Based on cell surface markers, we classified the platelets into 8 subpopulations (P0 to P7). Distinct subpopulations of platelets (P1, P4, and P5) exhibiting decreased aggregatory phenotype but altered secretory phenotypes were also identified and found to be more abundant in the blood of infants with CHD. Electron microscopy identified increased proportion of hypogranular platelets in CHD. Moreover, cytokine analysis demonstrated an overall increase in plasma cytokines and biomarkers in CHD, including IL (interleukin)-6, IL-8, IL-27, RANTES (regulated upon activation, normal T cell expressed and secreted), and VWF (von Willebrand factor), which are expressed in platelet granules and can be released upon activation.

CONCLUSIONS:

We developed a robust mass cytometry approach to identify platelet phenotypic heterogeneity. Infants with CHD had alterations in distinct subpopulations of platelets with overall reduced aggregatory phenotype and secretory dysfunction. These findings suggest that platelets in infants with CHD may be exhausted due to persistent stimulation and may explain both bleeding and thrombotic vascular complications associated with CHD.
Targeting the I
Ks
Channel PKA Phosphorylation Axis to Restore Its Function in High-Risk LQT1 Variants
Authors: Zhong Ling , Yan Zhenzhen , Jiang Dexiang , Weng Kuo-Chan , Ouyang Yue , Zhang Hangyu , Lin Xiaoqing , Xiao Chenxin , Yang Huaiyu , Yao Jing , Kang Xinjiang , Wang Changhe , Huang Chen , Shen Bing , Chung Sookja Kim , Jiang Zhi-Hong , Zhu Wandi , Neher Erwin , Silva Jonathan R. , Hou Panpan
Published: August 2024

BACKGROUND:

The KCNQ1+KCNE1 (I
Ks
) potassium channel plays a crucial role in cardiac adaptation to stress, in which β-adrenergic stimulation phosphorylates the I
Ks
channel through the cyclic adenosine monophosphate (cAMP)/PKA (protein kinase A) pathway. Phosphorylation increases the channel current and accelerates repolarization to adapt to an increased heart rate. Variants in KCNQ1 can cause long-QT syndrome type 1 (LQT1), and those with defective cAMP effects predispose patients to the highest risk of cardiac arrest and sudden death. However, the molecular connection between I
Ks
channel phosphorylation and channel function, as well as why high-risk LQT1 mutations lose cAMP sensitivity, remain unclear.

METHODS:

Regular patch clamp and voltage clamp fluorometry techniques were utilized to record pore opening and voltage sensor movement of wild-type and mutant KCNQ1/I
Ks
channels. The clinical phenotypic penetrance of each LQT1 mutation was analyzed as a metric for assessing their clinical risk. The patient-specific–induced pluripotent stem-cell model was used to test mechanistic findings in physiological conditions.

RESULTS:

By systematically elucidating mechanisms of a series of LQT1 variants that lack cAMP sensitivity, we identified molecular determinants of I
Ks
channel regulation by phosphorylation. These key residues are distributed across the N-terminus of KCNQ1 extending to the central pore region of I
Ks
. We refer to this pattern as the I
Ks
channel PKA phosphorylation axis. Next, by examining LQT1 variants from clinical databases containing 10 579 LQT1 carriers, we found that the distribution of the most high-penetrance LQT1 variants extends across the I
Ks
channel PKA phosphorylation axis, demonstrating its clinical relevance. Furthermore, we found that a small molecule, ML277, which binds at the center of the phosphorylation axis, rescues the defective cAMP effects of multiple high-risk LQT1 variants. This finding was then tested in high-risk patient-specific induced pluripotent stem cell–derived cardiomyocytes, where ML277 remarkably alleviates the beating abnormalities.

CONCLUSIONS:

Our findings not only elucidate the molecular mechanism of PKA-dependent I
Ks
channel phosphorylation but also provide an effective antiarrhythmic strategy for patients with high-risk LQT1 variants.