bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simulated exposures of oritavancin in in vitro pharmacodynamic models select for methicillin-resistant Staphylococcus aureus with reduced susceptibility to oritavancin but minimal cross-resistance or seesaw effect with other antimicrobials
Authors: Werth Brian J , Zhang Rutan , Barreras Beltran Ismael A , Penewit Kelsi , Waalkes Adam , Holmes Elizabeth A , Salipante Stephen J , Xu Libin 
Published: February 2025

Abstract

Background
Dalbavancin exposures select for VAN and daptomycin cross-resistance in Staphylococcus aureus often by walK-related mutations. Oritavancin is another long-acting lipoglycopeptide, but its proclivity to select for cross-resistance is unknown. The objective of this study was to determine if post-distributional pharmacokinetic oritavancin exposures select for meaningful susceptibility changes in S. aureus.

Methods
We simulated average post-distributional, free-drug exposures of oritavancin 1200 mg IV once (fCmax 11.2 µg/mL; β-elimination t1/2 13.4 h; γ-elimination t1/2 245 h) in an in vitro pharmacodynamic model for 28 days against five S. aureus including four MRSA. Samples were taken daily for colony enumeration and resistance screening. Susceptibility testing was repeated on isolates from resistance screening plates against oritavancin, vancomycin, daptomycin, dalbavancin and 6 beta-lactams with varying penicillin-binding protein affinities.

Results
Tested oritavancin exposures were bactericidal against 5/5 strains for 2–17 days before regrowth of less-susceptible subpopulations occurred. Isolates with reduced susceptibility to oritavancin were detected as early as 5 days, but the MIC increased above the susceptibility breakpoint (&gt;0.125 mg/L) in 4/5 strains eventually. Vancomycin and daptomycin MICs increased by 2- to 8-fold but did not exceed the susceptibility breakpoints in most isolates. β-lactam MICs were largely unchanged among the recovered isolates with reduced oritavancin susceptibility. Mutations were diverse but often involved purR with 13 unique variants identified among 4/5 strains.

Conclusions
Oritavancin-selected resistance was primarily associated with purR mutation and less frequently associated with cross-resistance and walK mutation than dalbavancin-selected resistance in similar strains and conditions. The reason for this is unclear but may stem from differences in the mechanism(s) and divergent mutational pathways.
Evaluation of dietary acid-binding capacity level on nursery pig growth performance and fecal dry matter
Authors: Stas Ethan B , Tokach Mike D , Woodworth Jason C , DeRouchey Joel M , Goodband Robert D , Gebhardt Jordan T 
Published: February 2025

Abstract
Two experiments were conducted to evaluate dietary acid-binding capacity-4 (ABC-4) level on weanling pig performance and fecal dry matter (DM). In both experiments, there were 5 pigs per pen and 12 replications per dietary treatment fed in two phases. In Exp. 1, 360 barrows, initially 5.9 kg, were allotted to 1 of 6 treatments. Five treatments were formulated with increasing ABC-4 ranging from 150 (low ABC-4) to 312 meq/kg (high ABC-4) in phase 1 and 200 (low ABC-4) to 343 meq/kg (high ABC-4) in phase 2. The low ABC-4 diet was formulated with specialty soy protein concentrate (SSPC; AX3 Digest, Protekta, Newport Beach, CA) and a combination of dietary acidifiers. Increasing ABC-4 was achieved by progressively replacing SSPC with enzymatically treated soybean meal (ESBM; HP 300, Hamlet Protein, Findlay, OH) on a standardized ileal digestible (SID) Lys basis and decreasing acidifiers. Diets were formulated to contain 100 mg/kg of Zn. For the sixth treatment, pharmacological levels of Zn from ZnO was added to the high ABC-4 diet. From d 0 to 23 and d 0 to 38, increasing ABC-4 increased then decreased (quadratic, P ≤ 0.046) ADG and ADFI. On d 10 and 17, increasing ABC-4 decreased (linear, P ≤ 0.022) fecal DM. From d 0 to 23, pigs fed the diet containing ZnO had increased (P ≤ 0.009) BW, ADG and ADFI compared to the high ABC-4 diet without ZnO. In Exp 2, 300 pigs, initially 6.0 kg, were allotted to 1 of 5 dietary treatments. Diet 1 was a low ABC-4 diet formulated to 200 and 250 meq/kg in phase 1 and 2, respectively. Two intermediate ABC-4 levels were formulated by either replacing SSPC with ESBM on an SID Lys basis (diet 2) or removing acidifiers (diet 3). Diet 4 was a high ABC-4 diet formulated by replacing SSPC and removing acidifiers to increase ABC-4. Diet 5 was diet 4 but with pharmacological levels of Zn from ZnO. Diets 1 through 4 contained 110 mg/kg of Zn. From d 0 to 24 and d 0 to 38, increasing ABC-4 decreased (linear, P ≤ 0.046) G:F. On d 10 and 24, increasing ABC-4 decreased (linear, P ≤ 0.005) fecal DM. From d 0 to 24, pigs fed the diet containing ZnO had increased (P ≤ 0.047) BW, ADG, ADFI, and G:F compared to the high ABC-4 diet without ZnO. In conclusion, an ABC-4 of 200 meq/kg from d 0 to 10 post-weaning and 250 meq/kg from d 10 to 24 post-weaning improves pig growth performance and fecal DM for compared to higher ABC-4 diets. In diets without ZnO, low ABC-4 diet formulation can improve performance and fecal DM of weanling pigs.
Evaluation of Low-Resistivity Reservoirs Based on the New Three-Water Model and Comprehensive Identification of Fluid Properties Using a Committee Machine-A Case Study of the Dongying Formation Member 1 Reservoir in the Gangdong Fault Zone
Authors: Chen Changwei , Pan Baozhi , Lin Xuechun , Zhang Pengji , Zhang Lihua , Ren Shulian , Xie Fei , Li Yan 
Published: February 2025

Abstract
Member 1 of the Dongying Formation in the Gangdong Fault Zone is characterized by shallow-water delta front deposits influenced by faults and sedimentation, which have led to the development of various lithological-structural micro oil reservoirs. The area's high irreducible water saturation and additional clay conductivity have contributed to the formation of low-resistivity reservoirs, complicating the identification of oil and gas layers. This has led to significant discrepancies between well-logging interpretations and actual production outcomes. Based on rock physics experiments and geological characteristics, this study identifies the main controlling factors of low-resistivity reservoirs and proposes specific identification criteria for these reservoirs. For the first time, a new three-water saturation model is applied in the quantitative evaluation of low-resistivity reservoirs in the study area, with processing results that align with production conclusions. By integrating the processing results from the new three-water model with multiple methods, the fluid properties are comprehensively assessed using a committee machine. This study establishes a set of well logging reservoir parameter evaluation methods specifically tailored for low-resistivity reservoirs, enhancing the accuracy of fluid identification and providing valuable insights for further promotion and application.
Diagnosis, clinical characteristics, and treatment of combined hepatocellular-cholangiocarcinoma
Authors: Terashima Takeshi , Harada Kenichi , Yamashita Taro 
Published: February 2025

Abstract
The concept and definition of combined hepatocellular-cholangiocarcinoma (cHCC-CCA), an extremely rare condition accounting for only 1% of all primary liver cancers, has shifted in recent years. The latest World Health Organization Classification (fifth edition) includes two types of cHCC-CCAs, (i) the classical type described in the previous edition, which contains a mixture of distinctly differentiated components of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) and (ii) intermediate cell carcinoma wherein all cells comprising the tumor express both hepatocellular and cholangiocellular features. However, the pathogenesis of cHCC-CCA, including its origins, remains controversial even among experts. Treatment strategies for cHCC-CCA in clinical practice have been determined based on imaging findings, tumor markers, and pathologically predominant tumor components for either HCC or ICC, suggesting that cHCC-CCA has yet to be been established as an independent disease entity. As with HCC and ICC, the treatment strategy for HCC-CCA involves initially considering resectability. Although systemic therapy has been considered for patients unsuitable for local treatment, no prospective clinical trials have evaluated the efficacy and safety of systemic therapy for cHCC-CCA, which could explain the lack of a standard of care. In recent years, however, studies have demonstrated the efficacy of immune checkpoint inhibitors for HCC and ICC, with therapeutic results having been reported for cHCC-CCA. Hence, further accumulation of cases is expected to facilitate the establishment of a consensus on treatment strategies in the near future.
Perturbations in levels of essential metals less severe in Parkinson's disease without dementia than in Parkinson's disease dementia
Authors: Scholefield Melissa , Church Stephanie J , Cooper Garth J S 
Published: February 2025

Abstract

Background
It is currently unknown why some individuals with Parkinson's disease (PD) go on to develop dementia (Parkinson's disease dementia; PDD), whereas others do not. One possibility is differences in susceptibility to metallomic dysregulation. A previous study of the PDD brain identified substantive perturbations in metal levels, including severe multi-regional decreases in Cu. The current work uses the same methods to ascertain whether this metallomic dysfunction is also present in the PD brain.

Methods
Tissue from nine PD cases free of cognitive decline and 15 equivalent controls was obtained from seven brain regions. Levels of Na, Mg, K, Ca, Mn, Fe, Cu, Zn, and Se were quantified using inductively coupled plasma mass spectrometry (ICP-MS). Multiple linear regression analysis was used to determine any potential confounder effects. Results were compared with those previously obtained for PDD.

Results
Decreased Cu in the medulla was the only statistically significant case–control difference observed in the PD brain; this contrasts markedly with the widespread metallic dysfunction observed in PDD. PD and PDD cases were well-separated by PCA analysis. In the PD cohort, tau Braak stage correlated with Cu concentrations in several regions, but these correlations were not retained when including PDD cases.

Conclusions
There is a marked difference in the metallomic profiles of PD and PDD, with an almost complete lack of metallic involvement observed in the former. This resistance to metallomic dysfunction may contribute to resilience against cognitive impairment in individuals with PD who do not develop dementia.
Doxycycline postexposure prophylaxis for bacterial STIs: Prescribing patterns, use, short-term outcomes among 2083 patients in a Los Angeles Federally Qualified Health Care Program, and implications for widespread use
Authors: Osmundson J , Holloway I W , Gil R M , Jann J T , Hong C , Bolan R K 
Published: February 2025

Abstract

Background
Rates of bacterial sexually transmitted infections (STIs) have risen dramatically over the past decades. Doxycycline postexposure prophylaxis (DP) is a novel intervention to prevent bacterial STIs. Recent randomized controlled clinical trials reported high DP efficacy at preventing syphilis and chlamydia in cisgender men who have sex with men (MSM) and transgender women.

Methods
We abstracted data from the Electronic Health Records of 2083 patients at the Los Angeles LGBT Center (the Center) who were prescribed DP between 2019 and June 2024. Patient information included race, income, gender, sex, DP prescriptions, and STI tests dating back to 1998.

Results
Over half of the patients prescribed DP patients at the Center were white, and 48.1% were between 31 and 40 years old. Most of these patients were not diagnosed with an STI in the previous year but ever having an STI correlated with early DP initiation. We demonstrate high real-world DP effectiveness in preventing infections with syphilis (86.4%) and chlamydia (89.7%), and moderate effectiveness for gonorrhea (54.7%), all remarkably similar to published clinical trials. DP use was highly variable, and DP failure for syphilis or chlamydia occurred only in patients with low DP use. There was similar effectiveness for chlamydia and gonorrhea regardless of anatomical site (rectal or throat swabs or urine sample).

Conclusions
We show that DP is highly effective at STI prevention in a real-world setting and describe patterns of DP prescribing and use, in addition to STI testing, that can directly inform best clinical practice.
An observational cohort study of bronchoalveolar lavage fluid galactomannan and Aspergillus culture positivity in patients requiring mechanical ventilation
Authors: Gao Catherine A , Markov Nikolay S , Pickens Chiagozie , Pawlowski Anna , Kang Mengjia , Walter James M , Singer Benjamin D , Wunderink Richard G 
Published: February 2025

Abstract

Background
Critically ill patients who develop invasive pulmonary aspergillosis have high mortality rates despite antifungal therapy. Diagnosis is difficult in these patients and incidences vary in the literature. Bronchoalveolar lavage (BAL) fluid galactomannan (GM) is a helpful marker, although the optimal cutoff is unclear.

Methods
This was a single-center cohort study of patients requiring mechanical ventilation in the medical ICU from June 2018-March 2023. Demographics, BAL, and outcome data were extracted from the electronic health record and compared between groups of patients who grew Aspergillus from BAL, those who had elevated BAL GM levels (&gt;0.5, &gt;0.8, or &gt;1.0) but did not grow Aspergillus, and those with neither.

Results
Of &gt;1700 BALs from 688 patients, only 18 BALs from 15 patients grew Aspergillus. Patients who grew Aspergillus had more intubated days (29 vs 11, p=0.002), and more ICU days (34 vs 15, p=0.002). BAL GM level was higher from samples that grew Aspergillus than those that did not (median ODI 7.08 vs 0.11, p&lt;0.001).

Conclusions
In this large cohort of critically ill patients, we found a low rate of Aspergillus growth and variable BAL GM elevation. These data suggest that the pre-test probability of IPA should be considered low in a general ICU population undergoing BAL evaluation to define the etiology of pneumonia. Elevated BAL GM may not reliably indicate invasive disease, but lack of culture positivity may also miss true infection. Improved scoring systems are needed to enhance pre-test probability for diagnostic test stewardship purposes, and tests must be interpreted in their own clinical contexts.
Mitigating overtreatment of ductal carcinoma in situ
Authors: Chung Hannah L , Moseley Tanya W , Wolverton Dulcy E , Whitman Gary J 
Published: February 2025

Abstract
Ductal carcinoma in situ (DCIS) represents a pathologic continuum between a high-risk lesion of the breast and an invasive cancer. Because death from breast cancer is linked to its metastatic spread, the major significance of DCIS is its potential to progress to an invasive cancer and the risk of an occult invasive cancer unrecognized until surgical excision is performed. The standard of care management for DCIS is a minimum of surgical excision, often coupled with adjuvant treatments. For approximately half of the DCIS cases that are at low risk for progression, standard of care treatment represents a potential overtreatment and the source of one of the main criticisms against screening. To minimize overtreatment, the tumor biology of any individual’s DCIS should be considered in the context of the patient’s age, medical co-morbidities, tolerance for risk, to tailor personalized treatments. Just as the management of some high-risk lesions of the breast have evolved to include non-surgical options, it makes sense to personalize the management offered to patients with DCIS. This article reviews the epidemiology, imaging, pathology, ongoing trials, current and possible future treatments of DCIS, comparing and contrasting it with classic high-risk breast lesions and invasive breast cancers.
Sleep Timing, Sleep Timing Regularity, and Cognitive Performance in Women Entering Late Adulthood: The Study of Women's Health Across the Nation (SWAN)
Authors: Swanson Leslie M , Hood Michelle M , Thurston Rebecca C , Butters Meryl A , Kline Christopher E , Kravitz Howard M , Avis Nancy E , Neal-Perry Genevieve , Joffe Hadine , Harlow Siobán D , Derby Carol A 
Published: February 2025

Abstract

Study Objectives
This study examined whether sleep timing and its regularity are associated with cognitive performance in older women and whether associations vary based on cardiometabolic risk factors.

Methods
The cross-sectional analysis included 1,177 community-dwelling females (mean age 65 years) from the observational Study of Women’s Health Across the Nation (SWAN) annual visit 15. Sleep timing (mean midpoint from sleep onset to wake-up) and its regularity (standard deviation of midpoint ) were assessed using actigraphy. Cognitive measures included immediate and delayed verbal memory, working memory, and processing speed. Cardiometabolic risk measures included central obesity, hypertension, diabetes, and the Atherosclerotic Cardiovascular Disease (ASCVD) risk score. Linear regression models, adjusted for covariates, tested associations between sleep and cognitive measures.

Results
After covariate adjustment, early sleep timing was associated with worse delayed verbal memory (β = -0.37; p = 0.047) and late sleep timing was associated with worse processing speed (β = -1.80; p = 0.008). Irregular sleep timing was associated with worse immediate (β = -0.29; p = 0.020) and delayed verbal memory (β = -0.36; p= 0.006), and better working memory (β = 0.50; p = 0.004). Associations between early sleep timing and delayed verbal memory strengthened as ASCVD risk increased (interaction β=-8.83, p=.026), and tsleep timing irregularity’s effect on-working memory was stronger among women with hypertension (interaction β = -3.35, p = .039).

Conclusions
Sleep timing and its regularity are concurrently associated with cognitive performance in older women. Cardiovascular disease risk may modify some of these associations. Future longitudinal studies are needed to clarify these relationships.
Dynamic Impacts of Sleep Disruption on Ecologically Assessed Affective, Behavioral, and Cognitive Risk Factors for Suicide: A Study Protocol
Authors: Bozzay Melanie L , Armey Michael F , Brick Leslie , Nugent Nicole , Huang Jeff , Goldschmidt Andrea B , Schatten Heather T , Primack Jennifer M , Saletin Jared M 
Published: February 2025

Abstract
Diminished sleep health is a known warning sign for suicide. However, the contexts and time periods within which diminished sleep elevates suicide risk are unknown. Modeling the complex process by which diminished sleep health impacts daily functioning and established proximal suicide risk factors can aid in addressing these important knowledge gaps. This paper describes the methods and research protocol for a study that aims to elucidate the nature of the sleep-suicide relationship and develop an integrated model of proximal suicide risk. Participants will be 200 adults at high-risk for suicide recruited from a psychiatric inpatient unit. They will complete a baseline assessment including clinical interviews and self-reports, and laboratory tasks with concurrent electroencephalography to phenotype relevant risk processes. This baseline assessment will be followed by four weeks of ecological momentary assessment and digital phenotyping, coupled with assessments of sleep via a wearable used to generate a minute-by-minute metric of cognitive effectiveness using the Sleep Activity, Fatigue, and Task Effectiveness algorithm (SAFTE) index. Follow-up assessments will be conducted 1-, 3-, and 6-months post hospital discharge to determine how the developed proximal model of risk prospectively predicts suicidal ideation and behavior. The results of this study have the potential to greatly enhance understanding of how and why diminished sleep health is related to real-world fluctuations in suicide risk, knowledge that can inform efforts to better prevent, and intervene to reduce suicides.
biGMamAct: efficient CRISPR/Cas9-mediated docking of large functional DNA cargoes at the ACTB locus
Authors: Pelosse Martin , Marcia Marco 
Published: February 2025

Abstract
Recent advances in molecular and cell biology and imaging have unprecedentedly enabled multi-scale structure-functional studies of entire metabolic pathways from atomic to micrometer resolution, and the visualization of macromolecular complexes in situ, especially if these molecules are expressed with appropriately-engineered and easily-detectable tags. However, genome editing in eukaryotic cells is challenging when generating stable cell lines loaded with large DNA cargoes. To address this limitation, here, we have conceived biGMamAct, a system that allows the straightforward assembly of a multitude of genetic modules and their subsequent integration in the genome at the ACTB locus with high efficacy, through standardized cloning steps. Our system comprises a set of modular plasmids for mammalian expression, which can be efficiently docked into the genome in tandem with a validated Cas9/sgRNA pair through homologous-independent targeted insertion (HITI). As a proof of concept, we have generated a stable cell line loaded with an 18.3-kilobase-long DNA cargo to express 6 fluorescently-tagged proteins and simultaneously visualize 5 different subcellular compartments. Our protocol leads from the in-silico design to the genetic and functional characterization of single clones within 6 weeks and can be implemented by any researcher with familiarity with molecular biology and access to mammalian cell culturing infrastructure.
Doxycycline: lights and shadows of a mysterious treatment for chronic rhinosinusitis
Authors: Hoang Minh P. , Seresirikachorn Kachorn , Snidvongs Kornkiat 
Published: February 2025

Purpose of review
Chronic rhinosinusitis (CRS) is a diverse condition, including different underlying pathophysiologies. Tailoring the treatment for CRS depends on the individual's specific endotype and phenotype rather than using a universal approach. The emergence of biologics in recent years has raised questions about the role of antibiotics, particularly doxycycline, in CRS management. Insights from existing research on the mechanisms and appropriate use of doxycycline therapy may guide physicians in selecting the right treatment target.

Recent findings
CRS with nasal polyps (CRSwNP) is frequently associated with type 2 inflammation and characterized by tissue remodeling process that can result in recalcitrant condition. Doxycycline therapy (100 mg daily) improves CRSwNP by exerting antitissue remodeling effects through matrix metalloproteinase inhibition. Doxycycline seems to provide benefits when used alongside adequate medicine treatment.

Summary
Current evidence on the use of doxycycline therapy is limited to a small number of high-quality studies. Further research is needed to explore the duration and factors of success of doxycycline in treating CRS. Like other antibiotics, doxycycline has limitations related to side effects and the potential for antibiotic resistance. Therefore, treatment decisions should be made with caution, especially when doxycycline is used in combination with other pharmacologic therapies.