bluuebunny/crossref_metadata_2025 huggingface dataset:
Enantioselective transformation of phytoplankton-derived dihydroxypropanesulfonate by marine bacteria
Authors: Liu Le , Gao Xiang , Dong Changjie , Wang Huanyu , Chen Xiaofeng , Ma Xiaoyi , Liu Shujing , Chen Quanrui , Lin Dan , Jiao Nianzhi , Tang Kai
Published: May 2024

Chirality, a fundamental property of matter, is often overlooked in the studies of marine organic matter cycles. Dihydroxypropanesulfonate (DHPS), a globally abundant organosulfur compound, serves as an ecologically important currency for nutrient and energy transfer from phytoplankton to bacteria in the ocean. However, the chirality of DHPS in nature and its transformation remain unclear. Here, we developed a novel approach using chiral phosphorus-reagent labeling to separate DHPS enantiomers. Our findings demonstrated that at least one enantiomer of DHPS is present in marine diatoms and coccolithophores, and that both enantiomers are widespread in marine environments. A novel chiral-selective DHPS catabolic pathway was identified in marine Roseobacteraceae strains, where HpsO and HpsP dehydrogenases at the gateway to DHPS catabolism act specifically on R-DHPS and S-DHPS, respectively. R-DHPS is also a substrate for the dehydrogenase HpsN. All three dehydrogenases generate stable hydrogen bonds between the chirality-center hydroxyls of DHPS and highly conserved residues, and HpsP also form coordinate–covalent bonds between the chirality-center hydroxyls and Zn2+, which determines the mechanistic basis of strict stereoselectivity. We further illustrated the role of enzymatic promiscuity in the evolution of DHPS metabolism in Roseobacteraceae and SAR11. This study provides the first evidence of chirality’s involvement in phytoplankton-bacteria metabolic currencies, opening a new avenue for understanding the ocean organosulfur cycle.
Three-years of dalbavancin use at a UK tertiary referral hospital serving a population with high numbers of people who inject drugs
Authors: Bresges Carolin , Bresges Kristina , Hewitt Claudette , Sharma Sunil , Davies Bethany
Published: May 2024

Background

Dalbavancin’s unique properties have led to an increase in its off-licence use in complex infection and in vulnerable populations including people who inject drugs (PWID), but data remain limited. In this retrospective cohort study, we describe the characteristics, treatment rationale and outcomes for all adult inpatients treated with dalbavancin at a UK tertiary hospital.

Results

Fifty-eight inpatients were treated with dalbavancin between 1 January 2018 and 1 January 2021, 98.3% for off-licence diagnoses. Acute bacterial skin and skin structure infection, infective endocarditis and endovascular infections were each diagnosed in 22.4% of patients. Bone and joint infections were diagnosed in 18.9%, discitis in 12.1% and central line-associated bloodstream infections in 5.2%. Sixty-nine percent of patients were bacteraemic; 52.5% Staphylococcus aureus, 5.0% MRSA. Two mild adverse reactions were attributed to dalbavancin. Treatment was successful in 43 (75.4%) patients, and failed in seven (12.3%). Seven (12.3%) were lost to follow-up.

Thirty-five patients (60.3%) were PWID, with low median age (41.0 years) and Charlson Comorbidity scores (0). Self-discharge was taken by 17.1% of PWID, and 20.6% were lost to follow-up. At 90 days, three (8.6%) PWID were deceased.

Conclusions

In this first UK cohort, dalbavancin was used off licence and in persons facing barriers to conventional therapies. Where data is available, it was safe and effective. Dalbavancin appears a potentially valuable tool in improving outcomes for PWID.
Antimicrobial resistance and ESBL production in uropathogenic Escherichia coli: a systematic review and meta-analysis in Ethiopia
Authors: Asmare Zelalem , Erkihun Mulat , Abebe Wagaw , Tamrat Ephrem
Published: May 2024

Background

Antimicrobial resistance (AMR) is a serious threat to global health systems. Escherichia coli is a major cause of urinary tract infections (UTIs). Understanding the AMR patterns of uropathogenic E. coli (UPEC) is crucial for effective public health interventions worldwide.

Objectives

This systematic review and meta-analysis aimed to consolidate existing research and provide a comprehensive information on AMR UPEC in Ethiopia.

Methods

We systematically searched databases such as PubMed, Web of Science, and Science Direct, along with including articles from Google Scholar. Data were extracted into Microsoft Excel and analysed using STATA 17.0. Cohen’s kappa was computed to assess reviewer agreement, while the I2 statistic evaluated heterogeneity. Egger’s tests were conducted to detect publication bias, and random-effects models were utilized to estimate the pooled resistance, with AMR rates for each antibiotic pooled separately.

Results

UPEC showed resistance rates, ranging from 3.64% (95% CI: −4.38% to 11.67%) for amikacin to 85.32% (95% CI: 78.6%–92.04%) for ampicillin. Highest resistance was to ampicillin (85.32%), followed by amoxicillin at 82.52% (95% CI: 74.3%–90.74%), tetracycline at 60.67% (95% CI: 51.53%–69.81%) and trimethoprim/sulfamethoxazole at 57.17% (95% CI: 49.93%–64.42%). Conversely, resistance rates were lower for amikacin at 3.64% and meropenem at 5.26% (95% CI: 2.64%–7.88%). UPEC demonstrated a pooled MDR rate of 79.17% (95% CI: 70.32%–88.01%) and a pooled ESBL production rate of 29.16% (95% CI: 22.36%–38.55%).

Conclusions

High levels of AMR were observed in UPEC strains, highlighting a critical public health issue requiring urgent action through robust antimicrobial stewardship and surveillance to preserve effective UTI treatment options.
Connected fragments: an early Hong Kong archaeological collection
Authors: Fraser Tullia C , Sung Agnes P Y , Chiesa Benjamin
Published: May 2024

During a refurbishment project at the University Museum and Art Gallery of the University of Hong Kong in 2018, a large collection of uncatalogued artefacts was discovered. Between February and September 2021 an internal project team conducted a preliminary review of this material, identifying it as an orphaned collection of bulk archaeological finds, largely from Hong Kong, collected in various excavations from the 1920s to 1967. This article offers an account of this reviewing exercise and provides insights into the histories of the formation and deposition of the collection. By identifying key individuals and the excavations involved, we situate the artefacts within the broader study of the development of archaeology in Hong Kong, and show that they constitute one of the earliest composite archaeological legacy collections in the city.
Rapid molecular species identification of mammalian scat samples using nanopore adaptive sampling
Authors: Frank Lexi E , Lindsey Laramie L , Kipp Evan J , Faulk Christopher , Stone Suzanne , Roerick Tanya M , Moore Seth A , Wolf Tiffany M , Larsen Peter A
Published: May 2024

Accurate taxonomic species identification is essential to the study of mammals. Despite this necessity, rapid and accurate identification of cryptic, understudied, and elusive mammals remains challenging. Traditional barcoding of mitochondrial genes is standard for molecular identification but requires time-consuming wet-lab methodologies. Recent bioinformatic advancements for nanopore sequencing data offer exciting opportunities for noninvasive and field-based identification of mammals. Nanopore adaptive sampling (NAS), a polymerase chain reaction (PCR)-free method, selectively sequences regions of DNA according to user-specified reference databases. Here, we utilized NAS to enrich mammalian mitochondrial genome sequencing to identify species. Fecal DNA extractions were sequenced from 9 mammals, several collected in collaboration with Minnesota Tribal Nations, to demonstrate utility for NAS barcoding of noninvasive samples. By mapping to the entire National Center for Biotechnology Information mammalian mitochondrial reference genome database and bioinformatically analyzing highly similar matches, we successfully produced species identifications for all fecal samples. Eight of 9 species identifications matched previous PCR or animal/fecal appearance-based identifications. For the ninth species, our genetic data indicate a misidentification stemming from the original study. Our approach has a range of applications—particularly in field-based wildlife research, conservation, disease surveillance, and monitoring of wildlife trade. Of importance to Minnesota tribes is invasive species monitoring, detections, and confirmation as climate impacts cause changes in biodiversity and shifts in species distributions. The rapid assessment techniques described here will be useful as new introductions and range expansions of native and invasive species may first be detected by the presence of signs such as scat rather than direct observations and will be helpful for chronically understaffed tribal natural resources agencies.
Negative strengthening: The interplay of evaluative polarity and scale structure
Authors: Gotzner Nicole , Mazzarella Diana
Published: May 2024

This work investigates absolute adjectives in the not very construction and how their pragmatic interpretation depends on the evaluative polarity and the scale structure of their antonymic pairs. Our experimental study reveals that evaluatively positive adjectives (clean) are more likely to be strengthened than evaluatively negative ones (dirty), and that maximum standard adjectives (clean or closed) are more likely to be strengthened than minimum standard ones (dirty or open). Our findings suggest that both evaluative polarity and scale structure drive the asymmetric interpretation of gradable adjectives under negation. Overall, our work adds to the growing literature on the interplay between pragmatic inference, valence and semantic meaning.
A peculiar presentation of tamponade: pericardial mesothelioma
Authors: Syed Ahmad Syed Danial , Kirk Frazer , Wijesinghe Wisalya , He Cheng , Stroebel Andrie
Published: May 2024

Pericardial mesothelioma (PM) is rare with only 200 cases recorded, and a post-mortem prevalence of <0.0022%. It is the third most common cardiac/pericardial tumour, behind angiosarcoma and rhabdomyosarcoma. PM incidence increases with age, typically incidentally diagnosed between 50 and 70 years, with a 3:1 male predominance. Occasional PM can cause chest pain, dyspnoea, cough and even dysphagia. PMs are often misdiagnosed with only 25% of cases being antemortem diagnoses. Unlike pleural mesothelioma, the link between asbestos exposure and malignancy is less convincing, with only 20% of cases having known exposure. 6 There are three histological types: epithelioid, fibrous (spindle cell), and biphasic (mixed). The average life-expectancy post diagnosis is 3–10 months. Due to the heterogeneity of the presentation and rarity there is no standardized management algorithm, and the diagnostic imaging or laboratory investigations are scarcely described. We are presenting one of the cases diagnosed in our unit here in the Gold Coast.
Salvage surgery for recurrent transdiaphragmatic thymoma in a patient not eligible for chemotherapy
Authors: Fabbri Giulia , Berjaoui Nabih , Lampridis Savvas , Bilkhu Rajdeep , Chauhan Ishaan , Kew Ee Phui , Patel Akshay , Bille Andrea
Published: May 2024

The recurrence rate following thymoma surgery has been reported to be as high as 29%. In cases of localized recurrence, complete resection can result in prolonged patient survival. However, surgery is rarely considered in cases of invasive recurrent thymomas with high disease burden. Here, we present the case of a woman with type B2 thymoma (Masaoka–Koga stage IVa) treated with surgery, chemotherapy, and radiotherapy. The disease recurred 6 years later, with invasion of the left lung and the 12th thoracic vertebra, as well as extension into the retroperitoneum. Due to the development of chemotherapy-associated toxicity, she underwent surgery with complete tumor resection and has remained free of disease at a 12-months follow-up. Radical surgery for recurrent invasive thymoma extending through the diaphragm is a feasible and safe therapeutic option in highly selected patients who are not eligible for systemic treatments.
Robotic-assisted partial nephrectomy for a neuroendocrine tumor in a horseshoe kidney: a case report
Authors: Kikkawa Kazuro , Maruno Kouhei , Hazama Tatsuya , Takahashi Toshifumi , Yamada Yuya , Nakashima Masakazu , Tamaki Masahiro , Ito Noriyuki
Published: May 2024

Neuroendocrine tumors of the kidney are exceedingly rare. We report the first case of robotic-assisted partial nephrectomy for such tumors in horseshoe kidneys. A 65-year-old woman was incidentally found to have a 27 mm renal mass in the isthmus of her horseshoe kidney during computed tomography. Based on contrast-enhanced computed tomography results, we initially suspected renal cell carcinoma originating from the horseshoe kidney. Subsequently, robotic-assisted partial nephrectomy with isthmus transection was performed. Intraoperatively, we adjusted the port position for camera insertion and the patient’s positioning to facilitate better visualization for dorsal isthmus and vessel dissection. Pathological examination and immunohistochemical analysis revealed a well-differentiated neuroendocrine tumor. Therefore, robotic-assisted partial nephrectomy is a safe and effective approach for managing neuroendocrine tumors in the isthmus of horseshoe kidneys. Given the nonspecific clinical presentation of renal neuroendocrine tumors and their rarity, the optimal management of these tumors remains controversial.
Malat1 affects transcription and splicing through distinct pathways in mouse embryonic stem cells
Authors: Aslanzadeh Morteza , Stanicek Laura , Tarbier Marcel , Mármol-Sánchez Emilio , Biryukova Inna , Friedländer Marc R
Published: May 2024

Malat1 is a long-noncoding RNA with critical roles in gene regulation and cancer metastasis, however its functional role in stem cells is largely unexplored. We here perform a nuclear knockdown of Malat1 in mouse embryonic stem cells, causing the de-regulation of 320 genes and aberrant splicing of 90 transcripts, some of which potentially affecting the translated protein sequence. We find evidence that Malat1 directly interacts with gene bodies and aberrantly spliced transcripts, and that it locates upstream of down-regulated genes at their putative enhancer regions, in agreement with functional genomics data. Consistent with this, we find these genes affected at both exon and intron levels, suggesting that they are transcriptionally regulated by Malat1. Besides, the down-regulated genes are regulated by specific transcription factors and bear both activating and repressive chromatin marks, suggesting that some of them might be regulated by bivalent promoters. We propose a model in which Malat1 facilitates the transcription of genes involved in chromatid dynamics and mitosis in one pathway, and affects the splicing of transcripts that are themselves involved in RNA processing in a distinct pathway. Lastly, we compare our findings with Malat1 perturbation studies performed in other cell systems and in vivo.
Immunogenicity of Current and Next-Generation Pneumococcal Conjugate Vaccines in Children: Current Challenges and Upcoming Opportunities
Authors: Feemster Kristen , Buchwald Ulrike K , Banniettis Natalie , Joyce Joseph G , Velentgas Priscilla , Chapman Timothy J , Yildirim Inci
Published: May 2024

Global use of pneumococcal conjugate vaccines (PCVs) with increasingly broader serotype coverage has helped to reduce the burden of pneumococcal disease in children and adults. In clinical studies comparing PCVs, higher-valency PCVs have met noninferiority criteria (based on immunoglobulin G geometric mean concentrations and response rates) for most shared serotypes. A numeric trend of declining immunogenicity against shared serotypes with higher-valency PCVs has also been observed; however, the clinical relevance is uncertain, warranting additional research to evaluate the effectiveness of new vaccines. Novel conjugation processes, carriers, adjuvants, and vaccine platforms are approaches that could help maintain or improve immunogenicity and subsequent vaccine effectiveness while achieving broader protection with increasing valency in pneumococcal vaccines.
Strain Differences in Bloodstream and Skin Infection: Methicillin-Resistant Staphylococcus aureus Isolated in 2018–2021 in a Single Health System
Authors: Hofstetter Katrina S , Jacko Natasia F , Shumaker Margot J , Talbot Brooke M , Petit Robert A , Read Timothy D , David Michael Z
Published: May 2024

Staphylococcus aureus is a common cause of skin and soft-tissue infections (SSTIs) and has become the most common cause of bloodstream infections (BSIs) in recent years, but whether the strains causing these two clinical syndromes overlap has not been studied adequately. USA300/500 (clonal complex [CC] 8–sequence type [ST] 8) and USA100 (CC5-ST5) have dominated among methicillin-resistant S aureus (MRSA) strains in the United States since the early 2000s. We compared the genomes of unselected MRSA isolates from 131 SSTIs with those from 145 BSIs at a single US center in overlapping periods in 2018–2021. CC8 MRSA was more common among SSTIs, and CC5 was more common among BSIs, consistent with prior literature. Based on clustering genomes with a threshold of 15 single-nucleotide polymorphisms, we identified clusters limited to patients with SSTI and separate clusters exclusively comprising patients with BSIs. However, we also identified eight clusters that included at least one SSTI and one BSI isolate. This suggests that virulent MRSA strains are transmitted from person to person locally in the healthcare setting or the community and that single lineages are often capable of causing both SSTIs and BSIs.
Nocardia Infection in Patients With Anti–Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies: A Prospective Multicenter French Study
Authors: Kerdiles Thibault , Lejeune Sophie , Portais Antoine , Bourgeois Gaelle , Lefevre Benjamin , Charmillon Alexandre , Sixt Thibault , Moretto Florian , Cornille Cyril , Vidal Magali , Coustillères François , Martellosio Jean-Philippe , Quenet Marion , Belan Martin , Andry Fanny , Jaffal Karim , Pinazo-Melia Angela , Rondeau Paul , Luque Paz David , Jouneau Stephane , Borie Raphael , Monnier Delphine , Lebeaux David ,   GM-Noc Study Group, Bergeron-Lafaurie Anne , Carpentier-Blanc Gabrielle , Cottin Vincent , Froidure Marie , Duverge Alice Hadchouel , Jouneau Stéphane , Laurent Frédéric , Lepeule Raphael , Lortholary Olivier , Mahévas Matthieu , Ménard Cédric , Rodriguez-Nava Véronica , Traclet Julie
Published: May 2024

Background

Nocardiosis, a bacterial opportunistic infection caused by Nocardia spp, has recently been reported in patients with anti–granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies, but insufficient data are available about disease presentation, outcomes, and occurrence of autoimmune pulmonary alveolar proteinosis (aPAP) in this population.

Methods

We performed a prospective, multicenter, nationwide study in France and included patients with a Nocardia infection who had anti-GM-CSF autoantibodies. We describe their clinical, microbiological, and radiological characteristics, and their outcome at 1 year of follow-up.

Results

Twenty patients (18 [90%] male) were included, with a median age of 69 (interquartile range, 44–75) years. The organs most frequently involved were the brain (14/20 [70%]) and the lung (12/20 [60%]). Half of the infections were disseminated (10/20 [50%]). Nocardia identification was predominantly made in abscess fluid (17/20 [85%]), among which 10 (59%) were brain abscesses. The 1-year all-cause mortality was 5% (1/20), and only 1 case of aPAP (1/20 [5%]) occurred during the follow-up period.

Conclusions

Nocardiosis with anti-GM-CSF autoantibodies is associated with a low mortality rate despite a high incidence of brain involvement. Although the occurrence of aPAP was infrequent during the 1-year follow-up period, long-term clinical data are needed to fully understand the potential relationship between nocardiosis, anti-GM-CSF autoantibodies, and aPAP.
The Data Crowd as a Legal Stakeholder
Authors: Kreiczer-Levy Shelly
Published: May 2024

This article identifies a new legal stakeholder in the data economy: the data crowd. A data crowd is a collective that: (i) is unorganised, non-deliberate and unable to form an agenda; (ii) relies on productive aggregation that creates an interdependency among participants; and (iii) is subjected to an external authority. Notable examples of crowds include users of a social network, users of a search engine and users of artificial intelligence-based applications. The law currently only protects users in the data economy as individuals, and in certain cases may address broad public concerns. However, it does not recognise the collective interests of the crowd of users and its unique vulnerability to platform power. The article presents and defends the crowd’s legal interests in a stable infrastructure for participation. It therefore reveals the need for a new approach to consumers’ rights in the data economy.
EGFR, HER2, and MET gene amplification and protein expression profiles in biliary tract cancer and their prognostic significance
Authors: Kim Yeseul , Jee Seungyun , Kim Hyunsung , Paik Seung Sam , Choi Dongho , Yoo Su Hyun , Shin Su-Jin
Published: May 2024

Background

There are limited conventional chemotherapy options for biliary tract cancers (BTCs), a heterogenous group of lethal, rare malignancies. The receptor tyrosine kinase (RTK) is closely associated with the progression of human malignancies through the regulation of cell cycle. Overexpression or amplification of RTKs has been investigated as a potential biomarker and therapeutic target in BTC; herein, we investigate the value of such interventions.

Materials and Methods

Overexpression of RTK proteins was examined by immunohistochemistry in 193 BTC samples, of which 137 were gallbladder carcinoma, 29 were perihilar cholangiocarcinoma, and 27 were intrahepatic cholangiocarcinoma. Silver in situ hybridization of MET and HER2 was performed to assess gene amplification.

Results

In the entire cancer group, gallbladder, perihilar, and intrahepatic, MET amplification rates were 15.7%, 19.0%, 3.4%, and 14.8%, respectively, and of HER2 amplification rates were 22.4%, 27.2%, 17.2%, and 3.7%, respectively. MET and HER2 protein expressions were significantly correlated with their gene amplification status. RTKs were significantly associated with adverse clinicopathologic features such as advanced pT category and lymph node metastasis. Overall survival was significantly shorter in MET-amplified (P = .024) and EGFR-overexpressed cases (P = .045). Recurrence-free survival was significantly correlated with HER2-amplified (P = .038) and EGFR-overexpressed cases (P = .046) in all patient groups. Overall and recurrence-free survival were significantly shorter in patients who were double positive for HER2 and EGFR.

Conclusion

Our data suggested that MET, HER2, and EGFR might be potential therapeutic targets and that their co-expression is a strong prognostic factor for BTCs.
Cross-Market Effects of Consolidation: Evidence from Banking
Authors: Bird Andrew , Du Ding , Karolyi Stephen A
Published: May 2024

The U.S. banking sector had nearly 70% fewer banks in 2022 relative to 1989, primarily because of mergers. We develop a methodology to estimate cross-market spillover effects of bank mergers and test whether the operations of incumbents facing consolidating competitors in one market are affected in other markets. We find that nonmerging banks within a market that are one standard deviation more exposed to mergers in other markets increase deposits by 2.1% relative to their less exposed competitors. Our methodology may be applied elsewhere to assess the aggregate impacts of industry consolidation and illustrates challenges with product-based or geographic market definitions.
Field science and scientific collaboration in the Svalbard Archipelago: beyond science diplomacy
Authors: Strouk Mayline , Maisonobe Marion
Published: May 2024

The presence of non-Arctic and non-European countries in the Arctic has been growing over the past two decades. Given the geographic distance of these countries from the polar region, their presence in the High North may seem surprising. In this article, we study the presence in Svalbard of scientists from different origins and how they interact through an analysis of the field missions in which they are involved. Combining network analysis and interviews, we highlight the role of the stations located in the archipelago for access to the field and the cooperation strategies of scientists, including those from countries that do not have stations above the Arctic Circle. We tackle issues of integration in this area by empirically discussing three logics: (1) scientific autonomy, (2) core-periphery structure, and (3) regional patterns of cooperation, thus going beyond an approach strictly limited to the analysis of science diplomacy policies.
Performance of several clinical scoring systems as predictors of adverse outcomes in acute exposure to toxic alcohols
Authors: Sharif Asmaa F , Shaheen Rakan S , Alsubaie Duhaim S , Alshabibi Rakan A , Abusamak Fahad W , AlNasser Shahd , Al-Mulhim Khalid A , Abdelgawad Inas I
Published: May 2024

Background

Toxic alcohols are chemicals with common metabolic characteristics resulting in severe morbidities and mortalities. The current study aimed to assess the efficacy of six scoring systems: The Poison Severity Score (PSS), Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, Rapid Acute Physiology Score (RAPS), Rapid Emergency Medicine Score (REMS), and Modified Early Warning Score (MEWS) in stratifying the patients exposed to toxic alcohol based on liability of organ failure, prolonged hospital stay, and need for an antidote.

Methods

A seven-year retrospective cross-sectional study was conducted using medical records of adult patients admitted to a poison control center.

Results

About 42.6% were complicated with adverse outcomes. Methanol was the worst toxic alcohol and the only cause of blindness and death. About 27.1% of methanol-exposed patients suffered from acute kidney injury, 15.3% suffered from hemodynamic instability and neurological dysfunction, and 8.5% suffered from respiratory failure. An APACHE II score above 8 was the best predictor of unfavorable outcomes, exhibiting the highest area under the curve (0.972), followed by the SOFA score. The APACHE II score was praised for being the best discriminator of an expected prolonged hospital stay. Yet, the simple scores, including RAPS and REMS, showed good performance as unfavorable outcome predictors with no significant variations to PSS, APACHE II score, and SOFA scores.

Conclusion

The current study concluded that though the APACHE II and SOFA scores were superior to others, the RAPS and REMS are good, simple, and effective alternatives, particularly when resources are restricted.
Changing selection on amino acid substitutions in Gag protein between major HIV-1 subtypes
Authors: Klink Galya V , Kalinina Olga V , Bazykin Georgii A
Published: May 2024

Amino acid preferences at a protein site depend on the role of this site in protein function and structure as well as on external constraints. All these factors can change in the course of evolution, making amino acid propensities of a site time-dependent. When viral subtypes divergently evolve in different host subpopulations, such changes may depend on genetic, medical, and sociocultural differences between these subpopulations. Here, using our previously developed phylogenetic approach, we describe sixty-nine amino acid sites of the Gag protein of human immunodeficiency virus type 1 (HIV-1) where amino acids have different impact on viral fitness in six major subtypes of the type M. These changes in preferences trigger adaptive evolution; indeed, 32 (46 per cent) of these sites experienced strong positive selection at least in one of the subtypes. At some of the sites, changes in amino acid preferences may be associated with differences in immune escape between subtypes. The prevalence of an amino acid in a protein site within a subtype is only a poor predictor for whether this amino acid is preferred in this subtype according to the phylogenetic analysis. Therefore, attempts to identify the factors of viral evolution from comparative genomics data should integrate across multiple sources of information.
Pain Education and Virtual Reality Improves Pain, Pain-related Fear of Movement, and Trunk Kinematics in Individuals With Persistent Low Back Pain
Authors: Window Peter , McGrath Michelle , Harvie Daniel S. , Smits Esther , Johnston Venerina , Murdoch Megan , Russell Trevor
Published: May 2024

Objectives:

To evaluate the effect of combining pain education and virtual reality (VR) exposure therapy using a cognitive-behavioral therapy-informed approach (virtual reality-based cognitive behavioral therapy [VR-CBT]) on pain intensity, fear of movement, and trunk movement in individuals with persistent low back pain.

Materials and Methods:

Thirty-seven participants were recruited in a single cohort repeated measures study, attending 3 sessions 1 week apart. The VR-CBT intervention included standardized pain education (session 1) and virtual reality-based exposure therapy (VRET; session 2) incorporating gameplay with mixed reality video capture and reflective feedback of performance. Outcome measures (pain intensity, pain-related fear of movement (Tampa Scale of Kinesiophobia), and trunk kinematics during functional movements (maximum amplitude and peak velocity) were collected at baseline (session 1) and 1 week after education (session 2) and VRET (session 3). One-way repeated measures analysis of variances evaluated change in outcomes from baseline to completion. Post hoc contrasts evaluated effect sizes for the education and VR components of VR-CBT.

Results:

Thirty-four participants completed all sessions. Significant (P < 0.001) reductions were observed in mean (SD) pain (baseline 5.9 [1.5]; completion 4.3 [2.1]) and fear of movement (baseline 42.6 [6.4]; completion 34.3 [7.4]). Large effect sizes (Cohen d) were observed for education (pain intensity: 0.85; fear of movement: 1.28), whereas the addition of VRET demonstrated very small insignificant effect sizes (pain intensity: 0.10; fear of movement: 0.18). Peak trunk velocity, but not amplitude, increased significantly (P < 0.05) across trunk movement tasks.

Conclusion:

A VR-CBT intervention improved pain, pain-related fear of movement, and trunk kinematics. Further research should explore increased VR-CBT dosage and mechanisms underlying improvement.
Experimentally Dissociating the Acute Mechanisms of Endplate Fracture Lesions and Schmorl's Node Injuries Using a Porcine Cervical Spine Model
Authors: Watson Michael I. , Zehr Jackie D. , Callaghan Jack P.
Published: May 2024

Study Design.

This is an in vitro biomechanical study.

Objective.

This study evaluated the influence of localized trabecular bone strength deficits and loading rate as determinants of Schmorl’s node and fracture lesion incidence. The failure load (ultimate compression tolerance [UCT]), loading stiffness, and failure morphology were assessed after acute compression loading and failure.

Summary of Background Data.

The cartilaginous endplate is vulnerable to injuries such as Schmorl’s nodes and fracture lesions. While both injuries are associated with acute compression traumas, the factors that distinguish their incidence are poorly understood.

Methods.

Forty-eight porcine spinal units (domestic hog, 5–10 mo, ~110 kg) were assigned to one of eight experimental groups that differed by initial condition (control, sham, experimentally produced chemical fragility, and structural void) and loading rate (3 kN/s, 9kN/s). A servo-hydraulic materials testing system was used to perform acute compression testing until observed failure in the specimen. Post-loading dissection was performed to classify injury morphologies. Between group differences in UCT and loading stiffness were evaluated using a general linear model and injury distributions were evaluated using chi-squared statistics.

Results.

Schmorl’s nodes occurred exclusively in chemical fragility (63%) and structural void groups (37%) and were more prevalent with a 9 kN/s (75%) loading rate compared with 3 kN/s (25%). In contrast, fracture lesions occurred in all FSUs assigned to the control groups (100%) and the majority of those assigned to the sham groups (92%). No between-group differences were observed for UCT and loading stiffness.

Conclusion.

Pre-existing strength deficits of the subchondral trabecular bone can alter endplate injury morphology, particularly when coupled with high loading rates, but the localized strength deficits that were associated with Schmorl’s nodes did not appreciably influence measured joint properties.
180- Versus 360-Degree Selective Laser Trabeculoplasty in Open Angle Glaucoma and Ocular Hypertension: A Systematic Review and Meta-Analysis
Authors: Zhu Daniel , Shah Paras P. , Wong Amanda , Zhang Charles , Barmas-Alamdari Daniel , Bouaziz Michael , Tirsi Andrew , Tello Celso
Published: May 2024

Précis:

This systematic review and meta-analysis found that 360-degree selective laser trabeculoplasty (SLT) is significantly more effective than 180-degree SLT at reducing intraocular pressure at 1-month and 1-year follow-ups without increased serious adverse event risk.

Purpose:

To determine the efficacy of 180- versus 360-degree selective laser trabeculoplasty (SLT) in adults with open angle glaucoma (OAG) and ocular hypertension (OHT).

Methods:

A systematic review was performed using PubMed, Embase, and Scopus databases, from 1995 to December 30, 2023, for studies comparing 180 and 360-degree SLT in adults with OAG and OHT (PROSPERO ID: CRD42024497832). Meta-analyses were performed to calculate nominal percent and raw reductions in intraocular pressure (IOP) between treatment groups at 1-month, 1-year, and 2-year follow-ups, as well as success rates, defined as a 20% or greater IOP reduction.

Results:

Nine studies with 1044 eyes were included; 491 received 180-degree SLT, and 553 received 360-degree SLT. At the 1-month follow-up, 360-degree SLT reduced IOP by 3.45% more (WMD=3.45; 95% CI: 2.02–4.88; P<0.00001) and 0.87 mm Hg more (WMD=0.87; 95% CI: 0.35–1.38; P=0.0010). At the 1-year follow-up, 360-degree SLT reduced IOP by 4.33% more (WMD=4.33; 95% CI: 2.35–6.32; P<0.0001) and 1.15 mm Hg more (WMD=1.15; 95% CI: 0.25–2.04; P=0.01). At 2 years of follow-up, 360-degree SLT reduced IOP by 4.86% more (WMD=4.86; 95% CI: −0.32, 10.0; P=0.07) and 1.25 mm Hg more (WMD=1.25; 95% CI: −0.29, 2.79; P=0.11); however, the difference was not statistically significant. Compared with 360-degree SLT, 180-degree SLT had a significantly lower success rate (OR=0.50; 95% CI: 0.35–0.72; P=0.0002). There was no difference in serious complications between interventions.

Conclusions:

360-degree SLT is more effective than 180-degree SLT at lowering IOP at 1-month and 1-year follow-ups as well as achieving successful IOP control without increased risk of serious complications.
Salmonella Bacteremia in Spanish Pediatric Emergency Departments: Uncommon But Not Mild
Authors: Garrido Rodríguez María , Alonso-Cadenas José Antonio , Gómez Borja , Gangoiti Iker , Hernández-Bou Susanna , de la Torre Espí Mercedes ,   Bacteremia Study Working Group from the Infectious Diseases Working Group, Spanish Society of Pediatric Emergencies (SEUP)
Published: May 2024

Background:

Salmonella spp. is an uncommon microorganism in bloodstream infections among pediatric patients in our setting, although in developing countries it is the most common causative organism in blood cultures.

Methods:

We describe the children presenting to pediatric emergency departments and diagnosed with Salmonella bacteremia (SB) and identify clinical and laboratory predictors of poor outcome (ie, complications, sequelae and death) by bivariate analysis. We performed an observational study and subanalysis of a multicenter prospective registry, including patients <18 years of age with a positive blood culture obtained at any of the 22 participating Spanish pediatric emergency departments between 2011 and 2016. We considered young age, chronic diseases, immunosuppressive treatment and intestinal flora disruption as risk factors for SB.

Results:

Of the 55 patients with SB (3.2% of registered bacteremia), 32 (58.2%) had no risk factors for SB, 42 (76.3%) had a normal pediatric assessment triangle and 45 (81.8%) an associated gastrointestinal infection (acute gastroenteritis or enteric fever). Nine (16.4%) had a poor outcome, including 1 death (1.8%). A poor outcome was more common in patients with an abnormal pediatric assessment triangle [odds ratio (OR): 51.6; 95% confidence interval (CI): 9.2–289.5], an altered physical examination (OR: 15.2; 95% CI: 4.4–58.8) and elevated C-reactive protein (OR: 1.01; 95% CI: 1.005–1.03).

Conclusions:

Most SBs were related to a gastrointestinal infection. One in 6 children had a poor outcome; abnormal pediatric assessment triangle on arrival (25% of patients) was the main risk factor identified.
A Pilot Study of a Trauma Resiliency Protocol for Law Enforcement Officers With Posttraumatic Stress Disorder Symptoms
Authors: Maguire Edward R. , de Andrade Thais Moreira , Melchor Brenda
Published: May 2024

Objective

The aim of the study is to test the efficacy of the 22ZERO Trauma Resiliency Protocol (TR-P) on posttraumatic stress disorder (PTSD) symptom severity among current and former law enforcement officers.

Methods

The study used a retrospective, pre/post intervention design to test the effects of the TR-P on measures of self-reported symptom severity.

Results

One hundred twenty-eight current and former law enforcement officers were exposed to the TR-P treatment. All participants were administered the PTSD Checklist for DSM-5 PTSD Checklist and other psychological assessments before and after exposure. Participants experienced a significant reduction in symptom severity, suggesting that exposure to the TR-P reduced the effects of PTSD in this sample of law enforcement officers.

Conclusions

The 22ZERO TR-P may be an efficacious mechanism for reducing PTSD symptom severity among current and former law enforcement officers. It should be tested using a randomized trial and a longer follow-up period.
Phenotypic, Genomic, and Transcriptomic Heterogeneity in a Pancreatic Cancer Cell Line
Authors: Xie Gengqiang , Zhang Liting , Usman Olalekan H. , Kumar Sampath , Modak Chaity , Patel Dhenu , Kavanaugh Megan , Mallory Xian , Wang Yue Julia , Irianto Jerome
Published: May 2024

Objective

To evaluate the suitability of the MIA PaCa-2 cell line for studying pancreatic cancer intratumor heterogeneity, we aim to further characterize the nature of MIA PaCa-2 cells' phenotypic, genomic, and transcriptomic heterogeneity.

Materials and Methods

MIA PaCa-2 single-cell clones were established through flow cytometry. For the phenotypic study, we quantified the cellular morphology, proliferation rate, migration potential, and drug sensitivity of the clones. The chromosome copy number and transcriptomic profiles were quantified using SNPa and RNA-seq, respectively.

Results

Four MIA PaCa-2 clones showed distinctive phenotypes, with differences in cellular morphology, proliferation rate, migration potential, and drug sensitivity. We also observed a degree of genomic variations between these clones in form of chromosome copy number alterations and single nucleotide variations, suggesting the genomic heterogeneity of the population, and the intrinsic genomic instability of MIA PaCa-2 cells. Lastly, transcriptomic analysis of the clones also revealed gene expression profile differences between the clones, including the uniquely regulated ITGAV, which dictates the morphology of MIA PaCa-2 clones.

Conclusions

MIA PaCa-2 is comprised of cells with distinctive phenotypes, heterogeneous genomes, and differential transcriptomic profiles, suggesting its suitability as a model to study the underlying mechanisms behind pancreatic cancer heterogeneity.
A Randomized Controlled Trial Comparing the Effect of Tracheostomy Training using Mannequin-Based Simulation and Smartphone Application on Self-Efficacy and Anxiety of Caregivers
Authors: Bahramnezhad Fatemeh , Jackson Alun C. , Mousavi Maryam , Mirmoghtadaie Zohreh Sadat , Asgari Amir
Published: May 2024

Inefficient education is a cause of anxiety and low self-efficacy among caregivers, especially for those caring for patients with tracheostomy. This randomized controlled trial aimed to compare the outcomes of tracheostomy care education by mannequin-based simulation and smartphone application. The participants were 126 primary caregivers of tracheostomy patients being discharged home from hospitals affiliated with Tehran University of Medical Sciences. The control group received routine care. Caregiver self-efficacy was assessed using the Caregiver Inventory and the Hamilton Anxiety Rating Scale prior to the education and 1 month after. There were significant differences among the three groups regarding the mean scores of self-efficacy and anxiety. There was a significant increase in self-efficacy (P ≤ .0001) and a significant decrease in anxiety (P ≤ .0001) scores after the intervention. The intergroup comparison showed a significant difference between the intervention groups and the control group in terms of changes in the anxiety and self-efficacy scores of caregivers (P < .001).
Assessment of Exercise Capacity in Home Healthcare
Authors: Dias Konrad J. , McPherson Abigail , Mason Katherine , Dowling Kelsey , Smith-Beaver Lauren P. , Nadler Dustin R.
Published: May 2024

Submaximal functional tests of endurance are ubiquitous in clinical practice. This investigation compared cardiovascular responses, perceived exertion, and performance measures following the completion of three self-paced, 2-minute, functional tests of endurance. A pilot prospective, observational, cross-sectional design with 16 community-dwelling older participants compared heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), rating of perceived exertion (RPE), and performance measures following the completion of three randomly allocated self-paced activities. The three activities included 2 minutes of stepping in standing (2MSTD), 2 minutes of seated stepping (2MSIT), and a 2-minute walk test (2MWT). A within-subjects repeated measures ANOVA analyzed differences in change scores for cardiovascular and RPE responses. Pearson's correlations assessed associations in performance measures between the three tests. Standing stepping compared to seated stepping produced statistically higher change scores in HR, SBP, DBP, and RPE (p < .05). Further, 2MSTD revealed statistically higher SBP and RPE scores compared to 2MWT (p < .05). Large and moderate correlations were observed between number of steps completed in sitting and standing (r = 0.83, p < .01) and between standing steps and distance walked (r = 0.56, p = .02), respectively. This pilot investigation informs home care physical therapists that 2 minutes of self-paced stepping in standing produced the greatest change scores in all cardiovascular and perceived exertion responses. No significant differences were noted in HR between self-paced walking and standing stepping, and between standing and seated stepping. For patients unable to walk or step in standing, self-paced seated stepping may be a viable alternative.
10-Day Theta Burst Stimulation Intervention Facilitates the Clinical Rehabilitation of Patients After an Isolated Limb Fracture
Authors: Jodoin Marianne , Herrero Babiloni Alberto , Provost Catherine , Blais Hélène , Bellemare Audrey , Desjardins Martine , Rouleau Dominique M. , De Beaumont Louis
Published: May 2024

Objective

We investigated if theta burst stimulation could enhance recovery by reducing key symptoms when implemented acutely postfracture in participants with an isolated upper limb fracture.

Methods/Design

This was a pilot study with a randomized matched pair, sham-controlled, participant-blind design of a 10-day prolonged continuous theta burst stimulation protocol. Two main groups were included: I) participants with isolated upper limb fracture receiving active theta burst stimulation and II) patients with isolated upper limb fracture receiving SHAM/placebo. Another group (III) of healthy individuals was the reference group. Disability and pain intensity were collected through questionnaires (disabilities of the Arm, Shoulder, and Hand as well as numerical rating scale (NRA)) at three time points (baseline; 72 hrs after intervention, 3 mos after injury). Group III completed the baseline assessment.

Results

Seventy-nine participants were enrolled. Individuals in the ACTIVE and SHAM groups had similar baseline measures. For disability, the interaction between intervention and time approached significance (F = 2.33; P = 0.11), whereas it was significant for pain (F = 3.42; P = 0.04). At 3 mos after injury, the ACTIVE group reported reduced disability (F = 4.71; P = 0.04) and pain (F = 5.84; P = 0.02) at 3 mos after injury compared to the SHAM group, with clinical measures from ACTIVE group being like controls.

Conclusions

In isolated upper limb fracture patients, a 10-day theta burst stimulation intervention implemented acutely posttrauma had beneficial effects on symptoms of functional recovery and pain at 3 mos after trauma.
Safety and Effectiveness From the Cabotegravir and Rilpivirine Implementation Study in European Locations Study: Phase 3b Hybrid Type III Implementation Study Integrating Cabotegravir + Rilpivirine Long-Acting Into European Clinical Settings
Authors: Jonsson-Oldenbüttel Celia , Ghosn Jade , van der Valk Marc , Florence Eric , Vera Francisco , De Wit Stéphane , Rami Agathe , Bonnet Fabrice , Hocqueloux Laurent , Hove Kai , Ait-Khaled Mounir , DeMoor Rebecca , Bontempo Gilda , Latham Christine L. , Gutner Cassidy A. , Iyer Supriya , Gill Martin , Czarnogorski Maggie , D'Amico Ronald , van Wyk Jean
Published: May 2024

Background:

Cabotegravir + rilpivirine long-acting (CAB + RPV LA) dosed every 2 months (Q2M) is a complete regimen for the maintenance of HIV-1 virologic suppression. In this study, we report month 12 clinical outcomes in patient study participants (PSPs) in the CAB and RPV Implementation Study in European Locations (CARISEL) study.

Setting:

CARISEL is a phase 3b implementation–effectiveness study.

Methods:

CARISEL was designed as a 2-arm, unblinded study with centers randomized to either enhanced or standard implementation arms. For PSPs, this study is single arm, unblinded, and interventional; all PSPs switched from daily oral therapy to CAB + RPV LA dosed Q2M. The primary objective was to evaluate the perceived acceptability, appropriateness, and feasibility of CAB + RPV LA implementation for staff participants (presented separately). Clinical secondary endpoints assessed through month 12 included the proportion of PSPs with plasma HIV-1 RNA ≥50 and <50 copies/mL (Snapshot algorithm), incidence of confirmed virologic failure (CVF; 2 consecutive plasma HIV-1 RNA levels ≥200 copies/mL), adherence to injection visit windows, and safety and tolerability.

Results:

Four hundred thirty PSPs were enrolled and treated; the mean age was 44 years (30% ≥50 years), 25% were women (sex at birth), and 22% were persons of color. At month 12, 87% (n = 373/430) of PSPs maintained HIV-1 RNA <50 copies/mL, with 0.7% (n = 3/430) having HIV-1 RNA ≥50 copies/mL. One PSP had CVF. The safety profile was consistent with previous findings. Overall, the results were similar between implementation arms.

Conclusion:

CAB + RPV LA Q2M was well tolerated and highly effective in maintaining virologic suppression with a low rate of virologic failure.