bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular magnetic resonance in the identification of extra-cardiac causes of myocarditis: a case series
Authors: Sakhi Hichem , Reverdito Guillaume , Soulat Gilles , Mousseaux Elie 
Published: May 2024

Abstract

Background
Myocarditis is challenging to diagnose due to its varied presentations. Endomyocardial biopsy is the gold standard for diagnosis, but its invasive nature has led to alternative non-invasive modalities, notably cardiovascular magnetic resonance (CMR). Identifying the precise aetiology of myocarditis is crucial for effective treatment, yet extra-cardiac causes are often overlooked. In this paper, we spotlight the underexplored role of CMR in diagnosing extra-cardiac aetiologies, utilizing three insightful cases for illustration.

Case summary
The first case is a 31-year-old patient with myocarditis secondary to a pyogenic liver abscess, identified through CMR, who improved after abscess drainage. The second case involves a 54-year-old patient with myocarditis attributed to adult T-cell leukaemia–lymphoma, with the loco-regional thickening process identified thanks to CMR. This patient had an unfavourable disease progression due to the underlying malignancy. The third case concerns a 23-year-old patient suffering from myocarditis associated with pneumonia, again illustrated effectively through CMR imaging, who recovered after antibiotic treatment.

Discussion
These cases underline the overlooked potential of CMR in diagnosing extra-cardiac aetiologies of myocarditis, even though such causes are rare. Despite current guidelines recognizing the importance of identifying the aetiology of myocarditis, they do not explicitly address the role of CMR in diagnosing extra-cardiac aetiologies. This article, therefore, proposes that future guidelines could emphasize the utility of CMR in exploring these causes, potentially leading to more accurate diagnoses and improved patient outcomes. It also advocates for a comprehensive, multidisciplinary approach to myocarditis diagnosis, encouraging vigilance for potential loco-regional causes, and calls for further research in this area.
Transcriptomic Signatures of Progression to Tuberculosis Disease Among Close Contacts in Brazil
Authors: Mendelsohn Simon C , Andrade Bruno B , Mbandi Stanley Kimbung , Andrade Alice M S , Muwanga Vanessa M , Figueiredo Marina C , Erasmus Mzwandile , Rolla Valeria C , Thami Prisca K , Cordeiro-Santos Marcelo , Penn-Nicholson Adam , Kritski Afranio L , Hatherill Mark , Sterling Timothy R , Scriba Thomas J ,   the RePORT–South Africa and RePORT–Brazil Consortia, Bilek Nicole , Cloete Yolundi , Erasmus Mzwandile , Fisher Michelle , Hadley Katie , Hassiem Rieyaat , Hatherill Mark , Jaxa Lungisa , Mbandi Stanley Kimbung , Mendelsohn Simon C , Meyer Faheemah , Muwanga Vanessa M , Nombida Onke , Penn-Nicholson Adam , Raphela Rodney , Scriba Thomas J , September Alison , Sterling Timothy R , Thami Prisca K , Veldsman Ashley , Andrade Alice , Andrade Bruno B , Carvalho Brenda , Cordeiro-Santos Marcelo , Figueiredo Marina Cruvinel , Gomes Adriano , Kritski Afranio L , Rolla Valeria C , Sterling Timothy R 
Published: May 2024

Abstract

Background
Approximately 5% of people infected with Mycobacterium tuberculosis progress to tuberculosis (TB) disease without preventive therapy. There is a need for a prognostic test to identify those at highest risk of incident TB so that therapy can be targeted. We evaluated host blood transcriptomic signatures for progression to TB disease.

Methods
Close contacts (≥4 hours of exposure per week) of adult patients with culture-confirmed pulmonary TB were enrolled in Brazil. Investigation for incident, microbiologically confirmed, or clinically diagnosed pulmonary or extrapulmonary TB disease through 24 months of follow-up was symptom triggered. Twenty previously validated blood TB transcriptomic signatures were measured at baseline by real-time quantitative polymerase chain reaction. Prognostic performance for incident TB was tested by receiver operating characteristic curve analysis at 6, 9, 12, and 24 months of follow-up.

Results
Between June 2015 and June 2019, 1854 close contacts were enrolled. Twenty-five progressed to incident TB, of whom 13 had microbiologically confirmed disease. Baseline transcriptomic signature scores were measured in 1789 close contacts. Prognostic performance for all signatures was best within 6 months of diagnosis. Seven signatures (Gliddon4, Suliman4, Roe3, Roe1, Penn-Nicholson6, Francisco2, and Rajan5) met the minimum World Health Organization target product profile for a prognostic test through 6 months and 3 signatures (Gliddon4, Rajan5, and Duffy9) through 9 months. None met the target product profile threshold through ≥12 months of follow-up.

Conclusions
Blood transcriptomic signatures may be useful for predicting TB risk within 9 months of measurement among TB-exposed contacts to target preventive therapy administration.
Review of Current Tuberculosis Human Infection Studies for Use in Accelerating Tuberculosis Vaccine Development: A Meeting Report
Authors: Balasingam Shobana , Dheda Keertan , Fortune Sarah , Gordon Stephen B , Hoft Daniel , Kublin James G , Loynachan Colleen N , McShane Helen , Morton Ben , Nambiar Sujatha , Sharma Nimisha Raj , Robertson Brian , Schrager Lewis K , Weller Charlotte L 
Published: May 2024

Abstract
Tools to evaluate and accelerate tuberculosis (TB) vaccine development are needed to advance global TB control strategies. Validated human infection studies for TB have the potential to facilitate breakthroughs in understanding disease pathogenesis, identify correlates of protection, develop diagnostic tools, and accelerate and de-risk vaccine and drug development. However, key challenges remain for realizing the clinical utility of these models, which require further discussion and alignment among key stakeholders. In March 2023, the Wellcome Trust and the International AIDS Vaccine Initiative convened international experts involved in developing both TB and bacillus Calmette-Guérin (BCG) human infection studies (including mucosal and intradermal challenge routes) to discuss the status of each of the models and the key enablers to move the field forward. This report provides a summary of the presentations and discussion from the meeting. Discussions identified key issues, including demonstrating model validity, to provide confidence for vaccine developers, which may be addressed through demonstration of known vaccine effects (eg, BCG vaccination in specific populations), and by comparing results from field efficacy and human infection studies. The workshop underscored the importance of establishing safe and acceptable studies in high-burden settings, and the need to validate &gt;1 model to allow for different scientific questions to be addressed as well as to provide confidence to vaccine developers and regulators around use of human infection study data in vaccine development and licensure pathways.
Altering the competitive environment of B cell epitopes significantly extends the duration of antibody production
Authors: Xu Hongke , Chen Yanfei , Li Jingzhi , Li Mengyu , Sun Miao , Chen Jian , Li Ling , Xue Qinghong , Ma Hongwei 
Published: May 2024

Abstract
Persistent immunoglobulin G (IgG) production (PIP) provides long-term vaccine protection. While variations in the duration of protection have been observed with vaccines prepared from different pathogens, little is known about the factors that determine PIP. Here, we investigated the impact of three parameters on the duration of anti-peptide IgG production, namely amino acid sequences, protein carriers, and immunization programs. We show that anti-peptide IgG production can be transformed from transient IgG production (TIP) to PIP, by placing short peptides (Pi) containing linear B cell epitopes in different competitive environments using bovine serum albumin (BSA) conjugates instead of the original viral particles. When goats were immunized with the peste des petits ruminants (PPR) live-attenuated vaccine (containing Pi as the constitutive component) and BSA-Pi conjugate, anti-Pi IgG production exhibited TIP (duration &lt; 60 days) and PIP (duration &gt; 368 days), respectively. Further, this PIP was unaffected by subsequent immunization with the PPR live-attenuated vaccine in the same goat. When goats were coimmunized with PPR live-attenuated vaccine and BSA-Pi, the induced anti-Pi IgG production showed a slightly extended TIP (from ~60 days to ~100 days). This discovery provides new perspectives for studying the fate of plasma cells in humoral immune responses and developing peptide vaccines related to linear neutralizing epitopes from various viruses.
Human bronchopulmonary disposition and plasma pharmacokinetics of oral bemnifosbuvir (AT-527), an experimental guanosine nucleotide prodrug for COVID-19
Authors: Zhou Xiao-Jian , Horga Arantxa , Puri Adeep , Winchester Lee , Montrond Maureen , Pietropaolo Keith , Belanger Bruce , Fletcher Courtney V , Hammond Janet 
Published: May 2024

Abstract

Background
Bemnifosbuvir (AT-527) is a novel oral guanosine nucleotide antiviral drug for the treatment of persons with COVID-19. Direct assessment of drug disposition in the lungs, via bronchoalveolar lavage, is necessary to ensure antiviral drug levels at the primary site of SARS-CoV-2 infection are achieved.

Objectives
This Phase 1 study in healthy subjects aimed to assess the bronchopulmonary pharmacokinetics, safety and tolerability of repeated doses of bemnifosbuvir.

Methods
A total of 24 subjects were assigned to receive bemnifosbuvir twice daily at doses of 275, 550 or 825 mg for up to 3.5 days.

Results
AT-511, the free base of bemnifosbuvir, was largely eliminated from the plasma within 6 h post dose in all dosing groups. Antiviral drug levels of bemnifosbuvir were consistently achieved in the lungs with bemnifosbuvir 550 mg twice daily. The mean level of the guanosine nucleoside metabolite AT-273, the surrogate of the active triphosphate metabolite of the drug, measured in the epithelial lining fluid of the lungs was 0.62 µM at 4–5 h post dose. This exceeded the target in vitro 90% effective concentration (EC90) of 0.5 µM for antiviral drug exposure against SARS-CoV-2 replication in human airway epithelial cells. Bemnifosbuvir was well tolerated across all doses tested, and most treatment-emergent adverse events reported were mild in severity and resolved.

Conclusions
The favourable pharmacokinetics and safety profile of bemnifosbuvir demonstrates its potential as an oral antiviral treatment for COVID-19, with 550 mg bemnifosbuvir twice daily currently under further clinical evaluation in persons with COVID-19.
Sedimentation field-flow fractionation for rapid phenotypic antimicrobial susceptibility testing: a pilot study
Authors: Gauthier Audrey , Tlili Linda , Battu Serge , Le Moan Coline , Ploy Marie-Cécile , Lalloue Fabrice , Bégaud Gaëlle , Barraud Olivier 
Published: May 2024

Abstract

Background
The increase in antibiotic resistance is a major public health issue. The development of rapid antimicrobial susceptibility testing (AST) methods is becoming a priority to ensure early and appropriate antibiotic therapy.

Objectives
To evaluate sedimentation field-flow fractionation (SdFFF) as a method for performing AST in less than 3 h.

Methods
SdFFF is based on the detection of early biophysical changes in bacteria, using a chromatographic-type technology. One hundred clinical Escherichia coli strains were studied. A calibrated bacterial suspension was incubated for 2 h at 37°C in the absence (untreated) or presence (treated) of five antibiotics used at EUCAST breakpoint concentrations. Bacterial suspensions were then injected into the SdFFF machine. For each E. coli isolate, retention times and elution profiles of antibiotic-treated bacteria were compared with retention times and elution profiles of untreated bacteria. Algorithms comparing retention times and elution profiles were used to determine if the strain was susceptible or resistant. Performance evaluation was done according to CLSI and the ISO standard 20776-2:2021 with broth microdilution used as the reference method.

Results
AST results from SdFFF were obtained in less than 3 h. SdFFF showed high categorical agreement (99.8%), sensitivity (99.5%) and specificity (100.0%) with broth microdilution. Results for each antimicrobial were also in agreement with the ISO 20776-2 recommendations, with sensitivity and specificity of ≥95.0%.

Conclusions
This study showed that SdFFF can be used as a rapid, accurate and reliable phenotypic AST method with a turnaround time of less than 3 h.
Pharmacist roles in antimicrobial stewardship: a qualitative study from India, South Africa and the United Kingdom
Authors: Nampoothiri Vrinda , Mbamalu Oluchi , Mendelson Marc , Singh Sanjeev , Charani Esmita 
Published: May 2024

Abstract

Objective
To explore pharmacist roles in antimicrobial stewardship (AMS) in India, South Africa (SA), United Kingdom (UK) and the factors that contribute to their participation in the programme in these countries.

Methods
Data were collected between April 2019 and March 2022 through semi-structured interviews with key AMS stakeholders from India (Kerala); SA (Western Cape province) and the UK (England). Interviews were conducted face to face or via Zoom and Skype platforms, audio recordings were transcribed verbatim and thematically analysed using a grounded theory approach aided by NVivo 12 software.

Results
We interviewed 38 key AMS stakeholders (pharmacists and doctors). India and the UK have dedicated AMS pharmacists (Doctor of Pharmacy and Master of Pharmacy graduates with opportunities for additional post-graduate qualifications respectively). Pharmacists in the UK lead AMS programmes, while in India, predominantly in the private sector, pharmacists drive AMS in collaboration with clinicians. In SA, pharmacists (Bachelor of Pharmacy graduates) participate in AMS out of their own commitment in addition to their pharmacy responsibilities. Private sector pharmacists drive AMS while public sector pharmacists participate in clinician-led AMS programmes. Current pharmacy curricula do not provide adequate training in AMS, and this limitation shapes pharmacist roles and acceptance in AMS among clinicians in India and SA. Support of mentors (doctors/senior pharmacists) and self-motivated learning are key factors for effective pharmacist involvement in AMS.

Conclusions
A contextually developed, standardized and accessible AMS training programme along with pharmacy curricula modification to include AMS, may facilitate prominent pharmacist roles in AMS.
Heat stress alters hematological parameters in barrows and gilts
Authors: Rudolph Tori E , Roths Melissa , Freestone Alyssa D , White-Springer Sarah H , Rhoads Robert P , Baumgard Lance H , Selsby Joshua T 
Published: May 2024

Abstract
The purpose of this investigation was to establish the role biological sex plays in circulating factors following heat stress (HS). Barrows and gilts (36.8 ± 3.7 kg body weight) were kept in either thermoneutral (TN; 20.8 ± 1.6 °C; 62.0% ± 4.7% relative humidity; n = 8/sex) conditions or exposed to HS (39.4 ± 0.6 °C; 33.7% ± 6.3% relative humidity) for either 1 (HS1; n = 8/sex) or 7 (HS7; n = 8/sex) d. Circulating glucose decreased as a main effect of the environment (P = 0.03). Circulating non-esterified fatty acid (NEFA) had an environment × sex interaction (P &lt; 0.01) as HS1 barrows had increased NEFA compared to HS1 gilts (P = 0.01) and NEFA from HS7 gilts increased compared to HS1 gilts (P = 0.02) and HS7 barrows (P = 0.04). Cortisol, insulin, glucagon, T3, and T4 were reduced as a main effect of environment (P ≤ 0.01). Creatinine was increased in HS1 and HS7 animals compared to TN (P ≤ 0.01), indicative of decreased glomerular filtration rate. White blood cell populations exhibited differential patterns based on sex and time. Neutrophils and lymphocytes had an environment × sex interaction (P ≤ 0.05) as circulating neutrophils were increased in HS1 barrows compared to TN and HS7 barrows, and HS1 gilts (P ≤ 0.01) and HS7 barrows had less neutrophils compared to TN barrows (P = 0.01), whereas they remained similar in gilts. In contrast, barrow lymphocyte numbers were similar between groups, but in HS7 gilts they were decreased compared to TN and HS1 gilts (P ≤ 0.04). In total, these data demonstrate that HS alters a host of circulating factors and that biological sex mediates, at least in part, the physiological response to HS.
Effects of baculovirus infection on intestinal microflora of BmNPV resistant and susceptible strain silkworm
Authors: Liu Shi-Huo , Zhang Ying , Guo Zhe-Xiao , Ayaz Sadaf , Wang Yan-Xiang , Huang Zhi-Hao , Cao Hui-Hua , Xu Jia-Ping 
Published: May 2024

Abstract
Bombyx mori L. (Lepidoptera: Bombycidae) nucleopolyhedrovirus (BmNPV) is a serious pathogen causing huge economic losses to sericulture. There is growing evidence that the gut microbiota of silkworms plays a critical role in shaping host responses and interactions with viral infection. However, little is known about the differences in the composition and diversity of intestinal microflora, especially with respect to silkworm strain differences and BmNPV infection-induced changes. Here, we aim to explore the differences between BmNPV-resistant strain A35 and susceptible strain P50 silkworm and the impact of BmNPV infection on intestinal microflora in different strains. The 16S rDNA sequencing analysis revealed that the fecal microbial populations were distinct between A35 and P50 and were significantly changed post BmNPV infection in both strains. Further analysis showed that the BmNPV-resistant strain silkworm possessed higher bacterial diversity than the susceptible strain, and BmNPV infection reduced the diversity of intestinal flora assessed by feces in both silkworm strains. In response to BmNPV infection, the abundance of Muribaculaceae increased in P50 and decreased in A35, while the abundance of Enterobacteriaceae decreased in P50 and increased in A35. These results indicated that BmNPV infection had various effects on the abundance of fecal microflora in different silkworm strains. Our findings not only broadened the understanding of host–pathogen interactions but also provided theoretical help for the breeding of resistant strains and healthy rearing of silkworms based on symbiotic bacteria.
Executing plans to enhance diversity across cancer centers in the United States: opportunities and challenges
Authors: Li Christopher I , Rogers Sherise Chantell , Bult Carol J , Guerra Carmen E , Talton Angela , Williams Lovoria B , Law Wendy 
Published: May 2024

Abstract

Background
Lack of diversity in the cancer research workforce persists, which the new requirement for all National Cancer Institute (NCI)–designated cancer centers to have a Plan to Enhance Diversity (PED) seeks to address. However, it is not well understood how different cancer centers are approaching the development and execution of these plans. Our objective was to assess how cancer centers are establishing and pursuing their PED.

Methods
We conducted a cross-sectional survey of members of the Cancer Center Diversity, Equity and Inclusion Network, which includes all NCI-designated cancer centers and several emerging centers. A total of 62 cancer centers (75% of those invited), including 58 NCI-designated cancer centers (81% of those with this designation), participated and completed a questionnaire that assessed PED leadership, major challenges, implementation strategies, and approach to evaluate PED progress.

Results
The most common PED challenge identified is recruiting diverse faculty (68% of centers), and the most common strategy currently used to address this is reviewing and revising faculty recruitment practices (67%). The most common approach centers are using to measure PED progress is shifts in demographics (68%), and data on the demographics of faculty, leadership, and trainees are available at 79%, 81%, and 75% of centers, respectively.

Conclusions
Almost all centers have established a PED leadership structure, however, there is considerable variation in the approaches used to realize PED goals and in the resources provided to support PED work. Realizing opportunities to share and implement common best practices and exemplar programs has the potential to elevate the impact of PED efforts nationally.
Paravertebral retroperitoneal ancient schwannoma mimicking irritable bowel syndrome
Authors: Muralidhar Venkiteswaran , Kundhavai Chandrasekaran , Modiem Ramvivek , Sowmya Singaram 
Published: May 2024

Abstract
We report a case of paravertebral retroperitoneal ancient schwannoma (RPAS) with symptoms suggestive of irritable bowel syndrome that was relieved after resection. Very few cases have been reported of RPAS with gastrointestinal symptoms. Increased bowel activity associated with RPAS has not been reported. Our case report suggests that RPAS may present with increased bowel frequency that could be relieved after surgical resection.
Endoleak after use of the fenestrated frozen elephant trunk technique to treat acute type A aortic dissection
Authors: Kanemura Takeyuki , Nakahara Yoshinori , Fukushima Toshiya , Kawamoto Shuhei , Morooka Kazuki , Shimozawa Motoharu 
Published: May 2024

Abstract
Several studies have indicated that the fenestrated frozen elephant trunk (FET) technique enhances early outcomes in cases of acute aortic dissection, although long-term outcomes remain unclear. A case involving a 62-year-old male who experienced endoleak from a fenestration site following total arch replacement using the fenestrated FET technique for a DeBakey type I aortic dissection is reported. The patient underwent successful reoperation involving total arch replacement and reinsertion of the FET. Postoperatively, there was an absence of endoleak from the fenestration, and a noteworthy reduction in the diameter of the aortic arch was observed. It is imperative to recognize that endoleak from a fenestration poses a risk for prompt aortic expansion, thus necessitating vigilant postoperative monitoring. Furthermore, when adopting fenestrated FET, it is crucial to ensure firm fixation around the fenestration to prevent endoleak.
Buparvaquone Induces Ultrastructural and Physiological Alterations Leading to Mitochondrial Dysfunction and Caspase-Independent Apoptotic Cell Death in Leishmania donovani
Authors: Majhi Swetapadma , Awasthi Bhanu Priya , Sharma Rakesh Kumar , Mitra Kalyan 
Published: May 2024

Abstract
Leishmaniasis is a neglected tropical disease (endemic in 99 countries) caused by parasitic protozoa of the genus Leishmania. As treatment options are limited, there is an unmet need for new drugs. The hydroxynaphthoquinone class of compounds demonstrates broad-spectrum activity against protozoan parasites. Buparvaquone (BPQ), a member of this class, is the only drug licensed for the treatment of theileriosis. BPQ has shown promising antileishmanial activity but its mode of action is largely unknown. The aim of this study was to evaluate the ultrastructural and physiological effects of BPQ for elucidating the mechanisms underlying the in vitro antiproliferative activity in Leishmania donovani. Transmission and scanning electron microscopy analyses of BPQ-treated parasites revealed ultrastructural effects characteristic of apoptosis-like cell death, which include alterations in the nucleus, mitochondrion, kinetoplast, flagella, and the flagellar pocket. Using flow cytometry, laser scanning confocal microscopy, and fluorometry, we found that BPQ induced caspase-independent apoptosis-like cell death by losing plasma membrane phospholipid asymmetry and cell cycle arrest at sub-G0/G1 phase. Depolarization of the mitochondrial membrane leads to the generation of oxidative stress and impaired ATP synthesis followed by disruption of intracellular calcium homeostasis. Collectively, these findings provide valuable mechanistic insights and demonstrate BPQ's potential for development as an antileishmanial agent.