bluuebunny/crossref_metadata_2025_split huggingface dataset:
P17 Hepatobiliary parasitic infestation: a case report
Authors: Al-Anee Omar , Bagwan Izhar , Gamage Amila 
Published: January 2024

Abstract

Background
Hepatic parasitic lesions can present with multiple cystic lesions that may simulate inflammatory pseudo-tumour or malignancy in appropriate clinical settings. Here we present a known case of renal cell carcinoma with liver lesions that showed parasitic infestation on histology.

Patient case
A 70-year-old male with a history of right partial nephrectomy for clear cell renal cell carcinoma having an uneventful postoperative follow-up for 2 years underwent a surveillance CT scan. Multiple hepatic cystic lesions were identified, which on subsequent MRI and PET scan were suspicious for metastasis. Partial hepatectomy was performed for histological evaluation.

Results
Multiple discrete cystic hepatic lesions were noted on macroscopy. Histological examination revealed multiple necrotic hyalinized nodules with granulomatous inflammation within the liver and dense neutrophil infiltration with microabscess formation. Within the central necrotic area, there were non-viable parasite eggs and parts of worm, in keeping with parasitic infestation. On further expert opinion, this was diagnosed as Enterobius infestation of liver.

Conclusions
Hepatobiliary parasitic infestations may be encountered as clinically and biochemically asymptomatic lesions, especially in immunocompromised patients. Strong clinical history of travel and parasite serology screen is always helpful to clinch the diagnosis but may not be always available during histological examination. This case highlights the importance of thorough histological and microbiological examination as all nodular lesions in liver are not malignant and could be infective.
P21 A Phase 3 randomized, double-blind, active comparator-controlled study to evaluate the safety, tolerability and immunogenicity of a 21-valent PCV, V116, in pneumococcal vaccine-naive adults (STRIDE-3)
Authors: Bruno Christopher , Buntinx Erik , Pelayo Enrique , Kamerbeek Jackie M , Garcia-Huidobro Diego , Barranco-Santana Elizabeth A , Sjoberg Folke , Song Joon Young , Greenberg David , Grijalva Carlos G , Orenstein Walter A , Morgan Leslie , Fernsler Doreen , Xu Weifeng , Waleed Muhammad , Li Jianing , Buchwald Ulrike K , Platt Heather L 
Published: January 2024

Abstract

Background
Pneumococcal disease (PD) prevention remains an unmet medical need in adults. V116 is an investigational pneumococcal conjugate vaccine (PCV) containing the most prevalent serotypes associated with PD in adults in regions with established paediatric vaccination programmes. This Phase 3 study evaluated safety, tolerability, and immunogenicity of V116 compared with PCV20 in adults.

Methods
Pneumococcal vaccine-naive adults ≥18 years were eligible. Cohort 1 (≥50 years, n=2362) was stratified by age (50–64, 65–74, 75–84 and ≥85) and randomized 1:1 to receive 1 dose of V116 or PCV20, and cohort 2 (18–49 years, n=301) was randomized 2:1 to receive 1 dose of V116 or PCV20. Pneumococcal serotype-specific opsonophagocytic activity (OPA) and IgG responses were measured at baseline (Day 1) and 30 days post vaccination (Day 30). Primary objectives included assessment of (i) non-inferiority of immune responses for the serotypes common to V116 and PCV20 in cohort 1; (ii) superiority of serotypes unique to V116 compared with PCV20 in cohort 1; and (iii) immunobridging from adults 18–49 to adults 50–64 for all 21 serotypes in V116. Safety was evaluated by the proportion of participants with adverse events (AEs).

Results
V116 is non-inferior to PCV20 for the 10 serotypes common to both vaccines as measured by serotype-specific OPA geometric mean titres (GMTs) at Day 30. V116 is superior to PCV20 for 10 of 11 unique serotypes as measured by OPA GMTs at Day 30 as well as based on the proportions of participants with a ≥4-fold rise in OPA from Day 1 to Day 30. V116 elicits comparable immune responses in participants 18–49 years compared with participants 50–64 years for the 21 serotypes in V116 as assessed by serotype-specific OPA GMTs at Day 30, successfully demonstrating immunobridging. In total, 61.7% and 67.2% of participants vaccinated with V116 and PCV20, respectively, had ≥1 AE. There were no vaccine-related serious AEs or vaccine-related deaths.

Conclusions
V116 elicits immune responses that are non-inferior to PCV20 for the common serotypes and superior to PCV20 for 10 of 11 unique serotypes in V116 and has a safety profile comparable to PCV20. This pivotal study supports V116 as a novel population-specific vaccine for the prevention of PD in adults.
P28 Evaluation of one in-house and three commercial phenotypic tests for detection of KPC, NDM and OXA-48-like carbapenemase in Klebsiella pneumoniae: is routine detection possible?
Authors: AlRujaibi Arwa , Rizvi Meher , Al Jabri Zaaima 
Published: January 2024

Abstract

Background
Phenotypic characterization of the OXA-48-like carbapenemase XDR and pandrug-resistant (PDR) Klebsiella pneumoniae in clinical isolates is essential for making informed empirical decisions and critical for strengthening antimicrobial stewardship programmes. This study focused on assessing one in-house and three commercial phenotypic tests for detection of KPC, NDM and OXA-48-like carbapenemases in an attempt to study the feasibility of making detection of OXA-48-like carbapenemases a routine activity of a diagnostic microbiology laboratory.

Methods
A total of 40 representative non-duplicate XDR and PDR clinical Klebsiella pneumoniae isolates were screened on the basis of susceptibility profile, resistance to piperacillin/tazobactam; susceptible, intermediate, or resistant to third generation cephalosporins; elevated MIC for meropenem. These isolates were then subjected to one in-house test (OXA-48 disc test) and three commercial tests: Xpert® Carba-R (Cepheid), MASTDISCS® Combi Carba Plus (D73C), Immunochromatographic assay (ICT); KPC/IMP/NDM/OXA-48 Combo test (LFIA), Medomics.

Results
Xpert ®Carba-R identified OXA-48 in 62.5% (n=25) isolates, NDM in 17.5% (n=7), KPC+NDM co-carriage in 15% (n=6) and KPC in one isolate. Both Xpert® Carba-R and ICT were considered as possible gold standards and the outcomes of the other tests were compared with these two. With Xpert® Carba-R as the gold standard, high sensitivity of 96.15% was detected in OXA-48-like isolates, followed by NDM (92.85%) and NDM+KPC (85.7%). The lowest sensitivity was seen with the OXA-48 disc test (48% in OXA-48, 53.8% in NDM) followed by D73C test (64% in OXA-48, 38.46% in NDM). These two tests could not detect co- carriage of NDM and KPC in six isolates, although in two cases one of the two was detected. Specificity was high among all the tests (96.29%–93.33%). With ICT as the gold standard, 100% sensitivity was reported for NDM and KPC isolates, followed by OXA-48 and KPC+NDM (96% and 83.33%, respectively). The specificity was higher with ICT (99%) than Xpert® Carba-R (96.29%) as in detection of co- carriage of NDM and KPC. In terms of cost ICT ($16 per test) was much cheaper than Xpert® Carba-R($52 per test).

Conclusions
We recommend immunochromatographic assay (ICT) as an excellent tool for detection of carbapenemases (KPC/IMP/NDM/OXA-48). OXA-48 disc test and MASTDISCS® Combi Carba plus (D73C) cannot be considered as good standard since they could not detect co-carriage of NDM and KPC and had lower sensitivity.
P29 Treatment outcomes with rezafungin and caspofungin in people aged 65 years and above with candidaemia and/or invasive candidiasis: integrated analysis of pooled Phase 2 and Phase 3 data
Authors: Cornely Oliver A , Thompson George R , Soriano Alex , Kullberg Bart-Jan , Kollef Marin , Vazquez Jose , Honore Patrick M , Bassetti Matteo , Pullman John , Dignani Cecilia , Das Anita F , Sandison Taylor , Pappas Peter G 
Published: January 2024

Abstract

Background
Factors including frailty and multimorbidity can affect candidaemia and/or invasive candidiasis (C/IC) treatment in older people.1 The current analysis explored data from C/IC patients aged ≥65 years who were treated with rezafungin or caspofungin in the STRIVE (Phase 2: NCT02734862) and ReSTORE (Phase 3: NCT03667690) clinical trials.2,3

Methods
STRIVE and ReSTORE were double-blind, randomized studies. Adults with C/IC, diagnosed by systemic signs and mycological confirmation, received rezafungin once-weekly (Week 1: 400 mg; Weeks 2–4: 200 mg) or once-daily caspofungin (Day 1: 70 mg; Days 2–28: 50 mg) by IV injection for ≥14 days (≤4 weeks). Post hoc analysis examined pooled STRIVE/ReSTORE data for subjects aged ≥65 years. Safety outcomes included treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) in subjects who received ≥1 dose of study drug (safety population). Day 30 all-cause mortality (ACM) and mycological response at Days 5 and 14 were examined for the modified intention-to-treat (mITT) population (subjects with mycological C/IC diagnosis within 96 h of randomization who received ≥1 study drug dose).

Results
The safety population included 132 subjects (rezafungin arm: 64; caspofungin arm: 68). The mITT population included 120 subjects (rezafungin arm: 57; caspofungin arm: 63). The most common TEAEs with rezafungin were hypokalaemia, diarrhoea, vomiting and anaemia (Table 1). Eight subjects reported rezafungin-related TEAEs and seven had caspofungin-related TEAEs. SAEs comprised one case each of first degree atrioventricular block (rezafungin arm) and acute liver injury (caspofungin arm). Day 30 ACM rate was 14.0% (rezafungin arm) and 31.7% (caspofungin arm). The between-group difference (95% CI) was -17.6 (−32.5, −2.8). Day 5 mycological response was 78.9% (rezafungin arm) and 58.7% (caspofungin arm; difference [95% CI]: 19.3 [3.3, 35.2]; Figure 1).

Conclusions
Integrated analysis of pooled STRIVE/ReSTORE study data revealed similar incidence of drug-related TEAEs and SAEs in patients aged ≥65 years treated with rezafungin or caspofungin. Further analyses are required to understand underlying factors influencing between-group differences regarding treatment outcomes.
Practical Considerations for Oncogenic Fusion Detection and Reporting in Solid Tumors
Authors: Solomon James P 
Published: January 2024

Abstract

Background
Chromosomal rearrangements that result in oncogenic fusions can hold tremendous clinical significance in solid tumors, often with diagnostic or treatment implications.

Content
Traditionally, low-throughput methods such as fluorescence in situ hybridization were used to identify fusions in the clinical laboratory. With the rise of next-generation sequencing techniques and the broad adoption of comprehensive genomic profiling, the practice of screening for fusions as part of an oncologic workup has evolved. RNA sequencing methods are increasingly used, as these comprehensive high-throughput assays have many advantages over traditional techniques. Several RNA sequencing platforms are available, each with benefits and drawbacks. Regardless of the approach, systematic evaluation of the RNA sequencing results and the fusions identified by the assay should be performed. Assessment of fusion events relies upon evaluation of quality evidence, structural evidence, and functional evidence to ensure accurate fusion reporting and interpretation.

Summary
Given the clinical significance of gene fusions in oncology, understanding the variety of assays available for fusion detection, their benefits and drawbacks, and how they are used in the identification and interpretation of gene fusions is important for the modern precision oncology practice.
FRAX predicts cardiovascular risk in women undergoing osteoporosis screening: the Manitoba bone mineral density registry
Authors: Ye Carrie , Schousboe John T , Morin Suzanne N , Lix Lisa M , McCloskey Eugene V , Johansson Helena , Harvey Nicholas C , Kanis John A , Leslie William D 
Published: January 2024

Abstract
Osteoporosis and cardiovascular disease (CVD) are highly prevalent in older women, with increasing evidence for shared risk factors and pathogenesis. Although FRAX was developed for the assessment of fracture risk, we hypothesized that it might also provide information on CVD risk. To test the ability of the FRAX tool and FRAX-defined risk factors to predict incident CVD in women undergoing osteoporosis screening with DXA, we performed a retrospective prognostic cohort study which included women aged 50 yr or older with a baseline DXA scan in the Manitoba Bone Mineral Density Registry between March 31, 1999 and March 31, 2018. FRAX scores for major osteoporotic fracture (MOF) were calculated on all participants. Incident MOF and major adverse CV events (MACE; hospitalized acute myocardial infarction [AMI], hospitalized non-hemorrhagic cerebrovascular disease [CVA], or all-cause death) were ascertained from linkage to population-based healthcare data.
The study population comprised 59 696 women (mean age 65.7 ± 9.4 yr). Over mean 8.7 yr of observation, 6021 (10.1%) had MOF, 12 277 women (20.6%) had MACE, 2274 (3.8%) had AMI, 2061 (3.5%) had CVA, and 10 253 (17.2%) died. MACE rates per 1000 person-years by FRAX risk categories low (10-yr predicted MOF &lt;10%), moderate (10%–19.9%) and high (≥20%) were 13.5, 34.0, and 64.6, respectively. Although weaker than the association with incident MOF, increasing FRAX quintile was associated with increasing risk for MACE (all P-trend &lt;.001), even after excluding prior CVD and adjusting for age. HR for MACE per SD increase in FRAX was 1.99 (95%CI, 1.96–2.02). All FRAX-defined risk factors (except parental hip fracture and lower BMI) were independently associated with higher non-death CV events.
Although FRAX is intended for fracture risk prediction, it has predictive value for cardiovascular risk.
Bone remodeling and responsiveness to mechanical stimuli in individuals with type 1 diabetes mellitus
Authors: Walle Matthias , Duseja Ankita , Whittier Danielle E , Vilaca Tatiane , Paggiosi Margaret , Eastell Richard , Müller Ralph , Collins Caitlyn J 
Published: January 2024

Abstract
Type 1 diabetes mellitus (T1DM) has been linked to increased osteocyte apoptosis, local accumulation of mineralized lacunar spaces, and microdamage suggesting an impairment of the mechanoregulation network in affected individuals. Diabetic neuropathy might exacerbate this dysfunction through direct effects on bone turnover, and indirect effects on balance, muscle strength, and gait. However, the in vivo effects of impaired bone mechanoregulation on bone remodeling in humans remain underexplored. This longitudinal cohort study assessed consenting participants with T1DM and varying degree of distal symmetric sensorimotor polyneuropathy (T1DM, n = 20, median age 46.5 yr, eight female) and controls (CTRL; n = 9, median age 59.0 yr, four female) at baseline and 4–yr follow-up. Nerve conduction in participants with T1DM was tested using DPNCheck and bone remodeling was quantified with longitudinal high–resolution peripheral quantitative–computed tomography (HR-pQCT, 82 μm) at the standard distal sites. Local trabecular bone formation (Tb.F) and resorption (Tb.R) sites were captured by implementing 3D rigid image registration of HR-pQCT images, and the mechanical environment across the bone microarchitecture at these sites was simulated using micro–finite element analysis. We calculated odds ratios to determine the likelihood of bone formation (ORF) and resorption (ORR) with increasing/decreasing strain in percent as markers for mechanoregulation. At the distal radius, Tb.F was 47% lower and Tb.R was 59% lower in T1DM participants compared with CTRL (P &lt; .05). Tb.F correlated positively with nerve conduction amplitude (R = 0.69, P &lt; .05) in participants with T1DM and negatively with glycated hemoglobin (HbA1c) (R = −0.45, P &lt; .05). Additionally, ORF was 34% lower and ORR was 18% lower in T1DM compared with CTRL (P &lt; .05). Our findings represent in vivo evidence suggesting that bone remodeling in individuals with T1DM is in a state of low responsiveness to mechanical stimuli, resulting in impaired bone formation and resorption rates; these correlate to the degree of neuropathy and level of diabetes control.
Fracture discrimination capability of ulnar flexural rigidity measured via Cortical Bone Mechanics Technology: study protocol for The STRONGER Study
Authors: Warden Stuart J , Dick Andrew , Simon Janet E , Manini Todd M , Russ David W , Lyssikatos Charalampos , Clark Leatha A , Clark Brian C 
Published: January 2024

Abstract
Osteoporosis is characterized by low bone mass and structural deterioration of bone tissue, which leads to bone fragility (ie, weakness) and an increased risk for fracture. The current standard for assessing bone health and diagnosing osteoporosis is DXA, which quantifies areal BMD, typically at the hip and spine. However, DXA-derived BMD assesses only one component of bone health and is notably limited in evaluating the bone strength, a critical factor in fracture resistance. Although multifrequency vibration analysis can quickly and painlessly assay bone strength, there has been limited success in advancing a device of this nature. Recent progress has resulted in the development of Cortical Bone Mechanics Technology (CBMT), which conducts a dynamic 3-point bending test to assess the flexural rigidity (EI) of ulnar cortical bone. Data indicate that ulnar EI accurately estimates ulnar whole bone strength and provides unique and independent information about cortical bone compared to DXA-derived BMD. Consequently, CBMT has the potential to address a critical unmet need: Better identification of patients with diminished bone strength who are at high risk of experiencing a fragility fracture. However, the clinical utility of CBMT-derived EI has not yet been demonstrated. We have designed a clinical study to assess the accuracy of CBMT-derived ulnar EI in discriminating post-menopausal women who have suffered a fragility fracture from those who have not. These data will be compared to DXA-derived peripheral and central measures of BMD obtained from the same subjects. In this article, we describe the study protocol for this multi-center fracture discrimination study (The STRONGER Study).
Fitness consequences of intraguild predation between Spodoptera frugiperda (Lepidoptera: Noctuidae) and Ostrinia furnacalis (Lepidoptera: Crambidae)
Authors: Sripontan Yuwatida , Wanthathaen Chatchaton , Chiu Chun-I 
Published: January 2024

Abstract
The introduction of the fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), into Thailand has significantly altered the dynamics of maize pests. It has overshadowed Ostrinia furnacalis (Guenée) (Asian corn borer) (Lepidoptera: Crambidae), previously the most severe maize insect in Thailand. This transition is postulated to stem from the superior intraguild predation (IGP) capabilities of S. frugiperda. To validate this supposition, we assessed the co-distribution patterns and damage locales of both pests within maize fields and analyzed the IGP’s repercussions on their larval growth, survival, and fecundity. Our findings demonstrate that: (i) incidence of O. furnacalis in maize fields is markedly reduced following the introduction of S. frugiperda; (ii) abundance of S. frugiperda and O. furnacalis is negatively correlated in field; (iii) interspecific interactions affect the spatial distributions of S. frugiperda and O. furnacalis on shared plants; (iv) S. frugiperda has lower generation time and higher fecundity; and (v) IGP amplifies the growth rate of S. frugiperda and elevates mortality in O. furnacalis. Moreover, in response to the competitive pressure exerted by S. frugiperda, O. furnacalis exhibited expedited molting and growth without a commensurate increase in size. Our data suggest IGP proficiency underpins S. frugiperda’s dominance in Thai maize fields. We propose a niche differentiation on spatiotemporal distribution facilitating the coexistence of S. frugiperda and O. furnacalis. The impact of S. frugiperda on pest management strategies is discussed.
Coarsening Natural Deduction Proofs I: Finding Perfect Proofs
Authors: Brauer Ethan 
Published: January 2024

Abstract
This paper explores how, given a proof, we can systematically transform it into a proof that contains no irrelevancies and which is as strong as possible. I define a weaker and stronger notion of what counts as a proof with no irrelevancies, calling them perfect proofs and gaunt proofs, respectively. Using classical core logic to study classical validities and core logic to study intuitionistic validities, I show that every core proof or classical core proof can be transformed into a perfect proof. In a sequel paper, I show how proofs in core logic can also be transformed into gaunt proofs and I observe that this property fails for classical core logic.
Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Subvariant Neutralization Following a Primary Vaccine Series of NVX-CoV2373 and BNT162b2 Monovalent Booster Vaccine
Authors: Babu Tara M , Shen Xiaoying , McClelland R Scott , Wang Zijun , Selke Stacy , Wilkens Chloe , Hauge Kirsten A , McClurkan Christopher L , Goecker Erin , Laing Kerry J , Koelle David M , Greninger Alexander L , Nussenzweig Michel C , Montefiori David C , Corey Lawrence , Wald Anna 
Published: January 2024

Abstract
We evaluated the immunologic response to a novel vaccine regimen that included 2 doses of NVX-CoV2373 (Novavax) followed by 1 dose of BNT162b2 (Pfizer-BioNTech) monovalent booster vaccine. A durable neutralizing antibody response to Omicron BA.4/BA.5 and BA.1 variants was observed at month 6 after the booster, while immune escape was noted for the XBB.1.5 variant.
Metastatic Undifferentiated Melanoma Mimicking a Primary Bone Tumor: A Potential Diagnostic Pitfall
Authors: Wills Abby , Dibbern Megan , Frierson Henry F. , Raghavan Shyam S. 
Published: January 2024

Abstract:
Undifferentiated melanoma (UM) is defined by the loss of classic morphologic and immunohistochemical melanocytic markers. Reports in the literature are rare and show that UM usually occurs as a metastasis in the setting of a known primary cutaneous melanoma. The most common mutations in UM include those involving BRAF, NRAS, and KIT, which are almost invariably present in the parent melanoma. In this study, we report a case of a primary sinonasal melanoma with metastatic UM presenting with osteoclast-like giant cells and resembling a primary bone tumor. The retention of an unusual KRAS mutation in UM that was also present in the primary lesion provided critical information for the diagnosis. Our report highlights the importance of considering mutational analysis to identify undifferentiated melanomas in patients with metastatic tumors which do not have the typical histopathologic and immunohistochemical features of melanoma.