bluuebunny/crossref_metadata_2025_split huggingface dataset:
DEFINE: A Prospective, Randomized, Phase 4 Trial to Assess a Protease Inhibitor–Based Regimen Switch Strategy to Manage Integrase Inhibitor–Related Weight Gain
Authors: Anderson David , Ramgopal Moti , Hagins Debbie P , Lee Johnnie , Simonson Richard Bruce , Hsu Tien-Huei , Xu Ping , Ahmad Nina , Short William R 
Published: September 2024

Abstract

Background
Integrase strand transfer inhibitor (INSTI)–based antiretroviral (ARV) therapies have been associated with greater weight gain in people living with human immunodeficiency virus (HIV) versus those on protease inhibitor (PI)–based regimens. The DEFINE study investigated whether switching from an INSTI- to a PI-based regimen could mitigate/reverse weight gain.

Methods
DEFINE (NCT04442737) was a randomized, 48-week, open-label, prospective, phase 4 study in virologically suppressed adults with HIV-1 and ≥10% weight gain on INSTI + tenofovir alafenamide (TAF)/emtricitabine (FTC; &lt;36 months prescreening). Participants either switched immediately to darunavir/cobicistat/FTC/TAF (D/C/F/TAF) or continued INSTI + TAF/FTC during weeks 0–24 then switched to D/C/F/TAF for weeks 24–48. The primary endpoint was least squares (LS) mean (95% confidence interval [CI]) percent weight change from baseline to week 24.

Results
Overall, 103 adults were randomized (D/C/F/TAF, n = 53; INSTI + TAF/FTC, n = 50); 30% were female, and 61% were Black/African American. No significant difference in weight change was observed at week 24 (LS mean change: D/C/F/TAF, 0.63% [95% CI, −.44% to 1.70%] vs INSTI + TAF/FTC, −0.24% [95% CI, −1.35% to .87%]; P = .24); however, a trend toward weight loss was observed with extended time post–ARV switch to D/C/F/TAF (baseline to week 48, −0.36% [95% CI, −1.77% to 1.06%]), particularly in subgroups at higher weight gain risk (eg, female and Black/African American participants). Metabolic endpoints paralleled weight change over time. D/C/F/TAF was well tolerated, with comparable virologic efficacy between arms.

Conclusions
While no significant change in body weight was observed at 24 weeks after switching from INSTI + TAF/FTC to D/C/F/TAF among adults with weight gain, a trend toward weight loss emerged with longer time post–ARV switch, supporting further investigation of ARV selection/switch for weight management.
Clinical Trials Registration. NCT04442737.
Prospective Exploratory Evaluation of Cepheid Xpert Mycobacterium tuberculosis Host Response Cartridge: A Focus on Adolescents and Young Adults
Authors: Seifert Marva , Catanzaro Donald G , Gracia Michael , Hillery Naomi , Tahseen Sabira , Masood Faisal , Hussain Alamdar , Majeed Uzma , Colman Rebecca E , Syed Rehan R , Catanzaro Antonino , Rodwell Timothy 
Published: September 2024

Abstract

Background
An accurate, rapid, non-sputum-based triage test for diagnosing tuberculosis (TB) is needed.

Methods
A prospective evaluation of the Cepheid GeneXpert Mycobacterium tuberculosis Host Response cartridge (Xpert-MTB-HR), a prototype blood-based host response mRNA signature assay, among individuals presenting with TB-like symptoms was performed in Pakistan and results were compared to 3 reference standards: Xpert MTB/RIF Ultra, bacteriological confirmation (Xpert MTB/RIF Ultra and/or culture positivity), and composite clinical diagnosis (clinician diagnosis, treatment initiation, Xpert MTB/RIF Ultra, and/or culture positivity). Analyses were conducted both for the entire study cohort and separately in the adolescent and young adult cohort (aged 10–24 years).

Results
A total of 497 participants, aged 6–83 years, returned valid Xpert-MTB-HR results. When a diagnostic threshold was set for a sensitivity of &gt;90%, specificity was 32% (95% confidence interval [CI], 28%–37%) compared to Xpert MTB/RIF Ultra, 29% (95% CI, 25%–34%) compared to a bacteriological confirmation, and 22% (95% CI, 18%–26%) compared to a composite clinical diagnosis. However, when evaluating only the adolescent and young adult cohort with a diagnostic threshold set for sensitivity of &gt;90%, specificity was 82% (95% CI, 74%–89%) compared to Xpert MTB/RIF Ultra, 84% (95% CI, 75%–90%) compared to a bacteriological confirmation, and 54% (95% CI, 44%–64%) compared to a composite clinical diagnosis.

Conclusions
While the Xpert-MTB-HR does not meet World Health Organization minimum criteria in the general population, in our study it does meet the minimum sensitivity and specificity requirements for a non-sputum-based triage test among adolescents and young adults when compared to Xpert MTB/RIF Ultra or bacteriological confirmation.
Intellectual Property and the European Courts, Conference at the Court of Justice of the European Union, Luxembourg, 5 June 2024
Authors: Khuchua Tamar , Galeotta Giorgia 
Published: September 2024

Abstract
On 5 June 2024, the German Association for Intellectual Property Law (GRUR) and the University of Luxembourg organised a conference on Intellectual Property and the European Courts at the Court of Justice of the European Union (CJEU) in Luxembourg. This one-day event featured fruitful discussions on the role of courts in protecting and enforcing intellectual property rights. Among the renowned speakers and moderators were judges from European courts, prominent attorneys, representatives of various organisations and associations, and leading academics from across Europe.
Statistical inference for sketching algorithms
Authors: Browne Ryan P , Andrews Jeffrey L 
Published: September 2024

Abstract
Sketching algorithms use random projections to generate a smaller sketched data set, often for the purposes of modelling. Complete and partial sketch regression estimates can be constructed using information from only the sketched data set or a combination of the full and sketched data sets. Previous work has obtained the distribution of these estimators under repeated sketching, along with the first two moments for both estimators. Using an alternative approach, we derive the distribution of the complete sketch estimator and additionally consider the error term under both repeated sketching and repeated sampling. Importantly, we obtain pivotal quantities which are based solely on the sketched data set—specifically not requiring information from the full data model fit. These pivotal quantities can be used for inference on the full data set regression estimates or the model parameters. For partial sketching, we derive pivotal quantities for a marginal test and an approximate distribution for the partial sketch under repeated sketching or repeated sampling—again avoiding reliance on a full data model fit. We extend these results to include the Hadamard and Clarkson–Woodruff sketches then compare them in a simulation study.
New Banach spaces-based mixed finite element methods for the coupled poroelasticity and heat equations
Authors: Careaga Julio , Gatica Gabriel N , Inzunza Cristian , Ruiz-Baier Ricardo 
Published: September 2024

Abstract
In this paper, we introduce and analyze a Banach spaces-based approach yielding a fully-mixed finite element method for numerically solving the coupled poroelasticity and heat equations, which describe the interaction between the fields of deformation and temperature. A nonsymmetric pseudostress tensor is utilized to redefine the constitutive equation for the total stress, which is an extension of Hooke’s law to account for thermal effects. The resulting continuous formulation, posed in suitable Banach spaces, consists of a coupled system of three saddle point-type problems, each with right-hand terms that depend on data and the unknowns of the other two. The well-posedness of it is analyzed by means of a fixed-point strategy, so that the classical Banach theorem, along with the Babuška–Brezzi theory in Banach spaces, allows to conclude, under a smallness assumption on the data, the existence of a unique solution. The discrete analysis is conducted in a similar manner, utilizing the Brouwer and Banach theorems to demonstrate both the existence and uniqueness of the discrete solution. The rates of convergence of the resulting Galerkin method are then presented. Finally, a number of numerical tests are shown to validate the aforementioned statement and demonstrate the good performance of the method.
Chemolithoautotrophic bacteria flourish at dark water–ice interfaces of an emerged Arctic cold seep
Authors: Delpech Lisa-Marie , Tveit Alexander T , Hodson Andrew J , Hand Kevin P , Kalenitchenko Dimitri 
Published: September 2024

Abstract
Below their ice shells, icy moons may offer a source of chemical energy that could support microbial life in the absence of light. In the Arctic, past and present glacial retreat leads to isostatic uplift of sediments through which cold and methane-saturated groundwater travels. This fluid reaches the surface and freezes as hill-shaped icings during winter, producing dark ice–water interfaces above water ponds containing chemical energy sources. In one such system characterized by elevated methane concentrations — the Lagoon Pingo in Adventdalen, Svalbard, Norway (~10 mg/L CH4, &lt;0.3 mg/L O2, −0.25°C, pH 7.9), we studied amplicons of the bacterial and archaeal (microbial) 16S rRNA gene and transcripts in the water pond and overlaying ice. We found that active chemolithoautotrophic sulfur-oxidizing microorganisms (Sulfurimonas, Thiomicrorhabdus) dominate a niche at the bottom of the ice that is in contact with the anoxic water reservoir. There, the growing ice offers surfaces that interface with water and hosts favorable physico-chemical conditions for sulfide oxidation. The detection of anaerobic methanotrophs further suggests that throughout the winter, a steady-state dark and cold methane sink occurs under the ice in two steps: first, methane is oxidized to carbon dioxide and sulfates are concomitantly reduced to sulfides by the activity of anaerobic methanotrophs (ANME) ANME-1a and sulfate-reducing bacteria (SRB) SEEP-SRB1 consortia; and second, energy from sulfides is used by sulfur-oxidizing microorganisms to fix carbon dioxide into organic carbon. Our results underscore that ice-covered and dark ecosystems are hitherto overlooked oases of microbial life and emphasize the need to study microbial communities in icy habitats.
Antiviral effect of Evusheld in COVID-19 hospitalized patients infected with pre-Omicron or Omicron variants: a modelling analysis of the randomized DisCoVeRy trial
Authors: Beaulieu Maxime , Gaymard Alexandre , Massonnaud Clément , Peiffer-Smadja Nathan , Bouscambert-Duchamp Maude , Carcelain Guislaine , Lingas Guillaume , Mentré France , Ader Florence , Hites Maya , Poignard Pascal , Guedj Jérémie 
Published: September 2024

Abstract

Background
The antiviral efficacy of Evusheld (AZD7442) in patients hospitalized for SARS-CoV-2 is unknown.

Methods
We analysed the evolution of both the nasopharyngeal viral load and the serum neutralization activity against the variant of infection in 199 hospitalized patients (109 treated with Evusheld, 90 treated with placebo) infected with the SARS-CoV-2 virus and included in the randomized, double-blind, trial DisCoVeRy (NCT04315948). Using a mechanistic mathematical model, we reconstructed the trajectories of viral kinetics and how they are modulated by the increase in serum neutralization activity during Evusheld treatment.

Results
Our model identified that the neutralization activity was associated with viral kinetics. Reflecting the variant-dependent neutralization activity of Evusheld, the antiviral activity of Evusheld was larger in patients infected with pre-Omicron or Omicron BA.2 variants than in patients infected with Omicron BA.1 variant. More specifically, the model predicted that Evusheld reduced the median time to viral clearance compared with placebo-treated patients by more than 5 days in patients infected by pre-Omicron (median: 5.9; 80% PI: 2.1–13.6) or Omicron BA.2 (median: 5.4; 80% PI: 2.0–12.4), respectively. The effect was more modest in patients infected by the Omicron BA.1 variant, reducing the median time to viral clearance by 2 days (median: 2.2; 80% PI: 0.4–8.9).

Conclusions
Hospitalized patients treated with Evusheld had a shorter median time to SARS-CoV-2 viral clearance. As Evusheld antiviral activity is mediated by the level of neutralization activity, its impact on viral clearance varies largely according to the variant of infection.
Emergence of high-level aztreonam–avibactam and cefiderocol resistance following treatment of an NDM-producing Escherichia coli bloodstream isolate exhibiting reduced susceptibility to both agents at baseline
Authors: Haidar Ghady , Kline Ellen G , Kitsios Georgios D , Wang Xiaohong , Kwak Eun Jeong , Newbrough Anthony , Friday Kelly , Hughes Kramer Kailey , Shields Ryan K 
Published: September 2024

Abstract

Background
Cefiderocol (FDC) or ceftazidime-avibactam with aztreonam (CZA-ATM) are frontline agents for New Delhi metallo-β-lactamase (NDM)-producing Enterobacterales; however, clinical data are scarce, and mechanisms of treatment-emergent resistance are ill-defined. Our objectives were to characterize serial isolates and stool microbiota from a liver transplant recipient with NDM-producing Escherichia coli bacteraemia.

Methods
Isolates collected pre- and post-CZA–ATM treatment underwent broth microdilution susceptibility testing and whole-genome sequencing. Longitudinal stool collected during CZA–ATM therapy underwent metagenomic sequencing (Nanopore MinION).

Results
The baseline isolate exhibited elevated MICs for ATM–AVI (16/4 µg/mL) and FDC (8 µg/mL). Posttreatment, a rectal surveillance isolate exhibited high-level resistance to ATM–AVI (&gt; 128/4 µg/mL) and FDC (32 µg/mL). Both isolates belonged to ST361 and harboured WT blaNDM-5. The baseline isolate contained wild type (WT) blaCMY-145 and mutations in ftsI (which encodes PBP3), including a YRIN insertion at residue 338 and the non-synonymous substitutions Q227H, E353K and I536L. The posttreatment isolate harboured new mutations in ftsI (A417 V) and blaCMY-145 (L139R and N366Y). Analysis of four stool samples collected during CZA–ATM treatment revealed high E. coli abundance. E. coli relative abundance increased from 34.5% (first sample) to 61.9% (last sample).

Conclusions
Baseline mutations in ftsI were associated with reduced susceptibility to ATM–AVI and FDC in an ST361 NDM-5-producing E. coli bloodstream isolate. High-level resistance was selected after CZA–ATM treatment, resulting in new ftsl and blaCMY-145 mutations. These findings underscore the need for ATM–AVI susceptibility testing for NDM producers, and the potential for PBP3 mutations to confer cross-resistance to ATM–AVI and FDC, which can emerge after CZA–ATM treatment.
A case of falling accident when carrying a thermos bottle in front of the body
Authors: Tatekawa Yukihiro , Tsuzuki Yukihiro , Fukuzato Yoshimitsu 
Published: September 2024

Abstract
Traumatic injury in children often involves traffic accidents, falls from height, bicycle accidents, abuse, and sports. We present our experience with a 6-year-old girl who bruised her abdomen by falling while running with a thermos bottle hanging diagonally across her neck and left shoulder, crossing in front of her body. After the injury, she was rushed to the hospital and plain abdominal computed tomography revealed free air, suggesting intestinal injury due to blunt trauma. She was transferred to our hospital, where abdominal examination revealed a bruise and redness at the umbilicus. There were signs of peritoneal irritation and guarding throughout the abdomen. Upright chest X-ray showed free air in the right subdiaphragmatic region. Laparoscopic inspection revealed one perforation and two serosal injuries. The damaged serosa was repaired, and the perforated intestine was resected and anastomosed. The patient was discharged on the 11th day following an uneventful postoperative course.
Nasopharyngeal and temporal bone abscess following necrotizing otitis externa: a case report
Authors: Alharthi Ahmad S , Almalki Zohour A , Alnafie Johara A , Althobaiti Hazem K , Ibrahim Mohamed M 
Published: September 2024

Abstract
Necrotizing otitis externa (NOE) is a severe infection primarily affecting the external auditory canal, seen mainly in immunocompromised individuals as patients with diabetes mellitus (DM). This case report highlights unusual complications of NOE: temporal bone and nasopharyngeal abscesses. These complications underscore the severity of NOE, particularly when caused by rare pathogens such as Klebsiella species. We detail the case of a 70-year-old male with uncontrolled DM who presented with severe right ear pain, purulent discharge, and significant postauricular swelling. Laboratory investigations revealed elevated inflammatory markers and poorly controlled diabetes. Cultures confirmed Klebsiella pneumoniae, and imaging showed diffuse edema and abscess formation in the temporal bone and nasopharynx. The patient was treated with intravenous Ceftazidime and ciprofloxacin for 6 weeks, followed by oral ciprofloxacin. Effective management of NOE necessitates a comprehensive, multidisciplinary approach. Early intervention, regular monitoring, and imaging are critical for promptly detecting and managing complications.
Rare confounder: benign multicystic peritoneal mesothelioma in a patient with mucinous colon adenocarcinoma
Authors: Patel Kruti K , Stinson Griffin P , Terracina Krista P , Nordenstam Johan F , Read Thomas E 
Published: September 2024

Abstract
Benign multicystic peritoneal mesothelioma (BMPM) is a rare condition, in which patients have multiple cystic lesions of the peritoneum. BMPM can mimic mucinous carcinomatosis and can thus create a diagnostic dilemma. We present the case of a 76-year-old woman who was referred for management of ascending colon adenocarcinoma and was noted to have several nonspecific cystic lesions in the abdomen and pelvis on preoperative computed tomography and diagnostic laparoscopy. Frozen section analysis suggested the lesions contained ‘mucin’. Due to concern for metastases, right colectomy was aborted. Final histologic analysis of the laparoscopic biopsies revealed mesothelial cysts, consistent with BMPM, unrelated to her colon adenocarcinoma. Laparoscopic right colectomy was performed 2 weeks later. BMPM can create diagnostic and therapeutic uncertainty in patients with known visceral malignancies when discovered incidentally. Frozen section analysis may not be accurate in differentiating the two, and final histologic confirmation should be sought prior to definitive treatment.
Deciphering the dynamic single-cell transcriptional landscape in the ocular surface ectoderm differentiation system
Authors: Zhang Canwei , Lin Zesong , Yu Yankun , Wu Siqi , Huang Huaxing , Huang Ying , Liu Jiafeng , Mo Kunlun , Tan Jieying , Han Zhuo , Li Mingsen , Zhao Wei , Ouyang Hong , Chen Xiangjun , Wang Li 
Published: September 2024

Abstract
The ocular surface ectoderm (OSE) is essential for the development of the ocular surface, yet the molecular mechanisms driving its differentiation are not fully understood. In this study, we used single-cell transcriptomic analysis to explore the dynamic cellular trajectories and regulatory networks during the in vitro differentiation of embryonic stem cells (ESCs) into the OSE lineage. We identified nine distinct cell subpopulations undergoing differentiation along three main developmental branches: neural crest, neuroectodermal, and surface ectodermal lineages. Key marker gene expression, transcription factor activity, and signaling pathway insights revealed stepwise transitions from undifferentiated ESCs to fate-specified cell types, including a PAX6 + TP63 + population indicative of OSE precursors. Comparative analysis with mouse embryonic development confirmed the model’s accuracy in mimicking in vivo epiblast-to-surface ectoderm dynamics. By integrating temporal dynamics of transcription factor activation and cell–cell communication, we constructed a comprehensive molecular atlas of the differentiation pathway from ESCs to distinct ectodermal lineages. This study provides new insights into the cellular heterogeneity and regulatory mechanisms of OSE development, aiding the understanding of ocular surface biology and the design of cell-based therapies for ocular surface disorders.
Rapid Loss of Nutritional Symbionts in an Endemic Hawaiian Herbivore Radiation Is Associated with Plant Galling Habit
Authors: Hansen Allison K , Argondona Jacob A , Miao Sen , Percy Diana M , Degnan Patrick H 
Published: September 2024

Abstract
Insect herbivores frequently cospeciate with symbionts that enable them to survive on nutritionally unbalanced diets. While ancient symbiont gain and loss events have been pivotal for insect diversification and feeding niche specialization, evidence of recent events is scarce. We examine the recent loss of nutritional symbionts (in as little as 1 MY) in sap-feeding Pariaconus, an endemic Hawaiian insect genus that has undergone adaptive radiation, evolving various galling and free-living ecologies on a single host-plant species, Metrosideros polymorpha within the last ∼5 MY. Using 16S rRNA sequencing, we investigated the bacterial microbiomes of 19 Pariaconus species and identified distinct symbiont profiles associated with specific host-plant ecologies. Phylogenetic analyses and metagenomic reconstructions revealed significant differences in microbial diversity and functions among psyllids with different host-plant ecologies. Within a few millions of years, Pariaconus species convergently evolved the closed-gall habit twice. This shift to enclosed galls coincided with the loss of the Morganella-like symbiont that provides the essential amino acid arginine to free-living and open-gall sister species. After the Pariaconus lineage left Kauai and colonized younger islands, both open- and closed-gall species lost the Dickeya-like symbiont. This symbiont is crucial for synthesizing essential amino acids (phenylalanine, tyrosine, and lysine) as well as B vitamins in free-living species. The recurrent loss of these symbionts in galling species reinforces evidence that galls are nutrient sinks and, combined with the rapidity of the evolutionary timeline, highlights the dynamic role of insect–symbiont relationships during the diversification of feeding ecologies. We propose new Candidatus names for the novel Morganella-like and Dickeya-like symbionts.
Acute heart failure with reduced ejection fraction following ozoralizumab in a patient with rheumatoid arthritis: A case report
Authors: Ito Takaaki , Miyoshi Yuji 
Published: September 2024

ABSTRACT
Ozoralizumab (OZR), a novel next-generation tumor necrosis factor (TNF) inhibitor with variable heavy-chain domains of heavy-chain-only antibodies, named Nanobody®, was approved in September 2022 as the sixth TNF inhibitor in Japan. Other previous TNF inhibitors have been associated with various adverse drug reactions (ADRs), including heart failure (HF). The real-world data on these rare but clinically significant ADRs associated with OZR is lacking. Herein, we report a case of an 81-year-old female patient with rheumatoid arthritis who was insufficiently responsive to previous TNF inhibitors and developed HF with reduced ejection fraction (HFrEF) after the first OZR administration. Her condition improved after OZR discontinuation, suggesting that OZR may have precipitated the HF with reduced ejection fraction despite tolerance with previous TNF inhibitors. Further studies are warranted to elucidate the mechanism and incidence of OZR-associated HF.