bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing neurosurgery clinic operations: a comparative study of interventions in Finland’s public healthcare system
Authors: Huttunen Jukka , Koivisto Timo
Published: November 2024

Background

The Finnish public healthcare system aims to ensure equal access to health services for all but faces challenges in meeting the demand for specialized care, such as neurosurgery, due to resource constraints. This study investigates interventions to increase resources at a neurosurgery outpatient clinic to improve patient care without compromising waiting times for diagnoses and treatments, leveraging Finland’s unique healthcare landscape.

Methods

The study was conducted at Kuopio University Hospital’s Department of Neurosurgery, the sole provider of neurosurgical care in Eastern Finland. Two interventions were designed to optimize clinic operations: one focusing on dynamic resource allocation through continuous monitoring and the other on establishing a fixed additional neurosurgeon slot. Process capability and regression analysis were employed to evaluate the effects of these interventions on the number of outpatient visits and the variability in daily patient numbers.

Results

The preliminary analysis showed an average of 9.3 outpatient visits per day (SD 5.2). The introduction of an additional neurosurgeon led to an increase of 5.014 visits per day, according to the regression analysis performed before the interventions. Following the interventions, the clinic observed an increase in the average number of daily outpatient visits to 9.8 after the first intervention and 11.6 after the second, with corresponding improvements in the number of neurosurgeons present. The second intervention, which established a predictable additional resource, resulted in a more significant improvement in process efficiency and stability. After the interventions, the number of new neurosurgical first patient visits increased by 7% (97 patients).

Conclusion

This study demonstrates the importance of structured and predictable resource allocation in enhancing the efficiency of specialized healthcare services, particularly in neurosurgery. It also underscores the potential of planned interventions to manage and improve patient care in a publicly funded healthcare system, despite the challenges posed by limited resources and the need for prioritization. Moreover, the findings highlight the necessity of ongoing measurement and analysis of development projects to ensure sustained improvement and avoid regression in process quality.
Proof of Concept: Autonomous Machine Vision Software for Botanical Identification
Authors: Stern Nathan , Leidig Jonathan , Wolffe Gregory
Published: November 2024

Background

High-performance thin-layer chromatography (HPTLC) is a widely used and accepted technique for identification of botanicals. Current best practices involve subjective comparison of HPTLC-generated images between test samples and certified botanical reference materials based on specific bands.

Objective

This research was designed to evaluate the potential of cutting-edge machine vision-based machine learning techniques to automate identification of botanicals using native HPTLC image data.

Method

HPTLC images from ginger and its closely related species and common adulterants were used to create large, synthetic datasets using a deep conditional generative adversarial network. This synthetic dataset was used to train and validate a deep convolutional neural network capable of automatically identifying new HPTLC image data. Performance of both neural networks was evaluated over time using appropriate loss functions as an indicator of their progress during learning. Validation of the overall system was measured via the accuracy of the learned model when applied to real HPTLC data.

Results

The machine vision system was able to generate realistic synthetic HPTLC images that were successfully used to train a deep convolutional neural network. The resulting learned model achieved high-accuracy identification from HPTLC images corresponding to ginger and six other related species.

Conclusions

A proof-of-concept HPTLC image-based machine vision system for the identification of botanicals was proven to be feasible, and a fully working prototype was validated for several species related to ginger.

Highlights

This use of an autonomous machine-vision system for botanical identification removed the subjectivity inherent to human-based evaluation. The learned model also accurately evaluated botanical HPTLC images significantly faster than its human counterpart, which could save both time and resources.
FraMiTrACR: A Sustainable and Economical Technology for Analytical Sample Preparation
Authors: Steils Jan-Michael , Kaluza Alexander , Schöne Klaus , Cashman John , Baumgartner Christian , Lang Maren , Kraus Melina
Published: November 2024

Background

There are several globally recognized methods for preparing laboratory samples. Of these, the Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) and Quick Polar Pesticides (QuPPe) methods are commonly used for food laboratory sample preparation. As an alternative, we developed a fractionation method using Fractionation of Milk for Trace Analysis of Contaminats and Residues (FraMiTrACR).

Objective

We present a life-cycle assessment for the QuEChERS, QuPPe, and FraMiTrACR methods. Our objective was to collect data to evaluate the carbon footprint of each method. However, as the ecological factors alone do not inform suitability of any given method, we also evaluated economic factors.

Methods

Our life cycle assessments (LCAs) followed ISO 14040/44 to determine the carbon footprint of each method. Also, we have analyzed existing data to support our comparison of all three methods.

Results

The mass of consumables and packaging for our FraMiTrACR method was observed to decrease by 45 and 34% from those required for the QuPPe and QuEChERS methods, respectively. Furthermore, we calculated a 43% reduction in carbon footprint when using FraMiTrACR compared to QuPPe and a 31% reduction compared to QuEChERS. In addition, we determined that our method offers time savings >87 and >71% compared to QuEChERS and QuPPe, respectively. The main economic benefit of FraMiTrACR comes from 84 and 70% labor cost savings compared to QuEChERS and QuPPe, respectively. The laboratory using the fractionation method can process 320 samples with FraMiTrACR within 8 h, an 87% increase in potential compared to QuEChERS and a 71% increase compared to QuPPe.

Conclusion

Fractionation using FraMiTrACR is a more sustainable method for analytical sample preparation, offering the same quality of results and far-reaching economic advantages.

Highlights

In comparison, FraMiTrACR uses up to 45% less consumables and packaging by weight and a reduction in kg CO2eq of up to 43%. In addition, the fractionation method offers up to 85% time-saving and up to an 84% reduction in labor cost per sample.
Proteomic and metabolomic profiling of aged pork loin chops reveals molecular phenotypes linked to pork tenderness
Authors: Johnson Logan G , Zhai Chaoyu , Prusa Kenneth J , Nair Mahesh N , Prenni Jessica E , Chaparro Jacqueline M , Huff-Lonergan Elisabeth , Lonergan Steven M
Published: November 2024

The ability to predict fresh pork tenderness and quality is hindered by an incomplete understanding of molecular factors that influence these complex traits. It is hypothesized that a comprehensive description of the metabolomic and proteomic phenotypes associated with variation in pork tenderness and quality will enhance the understanding and inform the development of rapid and nondestructive methods to measure pork quality. The objective of this investigation was to examine the proteomic and metabolomic profiles of ~2-wk aged pork chops categorized across instrumental tenderness groups. One hundred pork loin chops from a larger sample (N = 120) were assigned to one of the four categories (n = 25) based on instrumental star probe value (Category A, x¯ =4.23  kg, 3.43–4.55 kg; Category B, x¯ =4.79  kg, 4.66–5.00 kg; Category C, x¯ =5.43  kg, 5.20–5.64 kg; and Category D, x¯ =6.21  kg, 5.70–7.41 kg). Soluble protein from ~2 wk aged pork loin was prepared using a low-ionic-strength buffer. Proteins were digested with trypsin, labeled with 11-plex isobaric tandem mass tag reagents, and identified and quantified using a Q-Exactive Mass Spectrometer. Metabolites were extracted in 80% methanol from lyophilized and homogenized tissue samples. Derivatized metabolites were identified and quantified using gas chromatography-mass spectrometry. Between Categories A and D, 84 proteins and 22 metabolites were differentially abundant (adjusted P < 0.05). Fewer differences were detected in comparison between categories with less divergent tenderness measures. The molecular phenotype of the more tender (Category A) aged chops is consistent with a slower and less extended pH decline and markedly less abundance of glycolytic metabolites. The presence and greater abundance of proteins in the low-ionic-strength extract, including desmin, filamin C, calsequestrin, and fumarate hydratase, indicates a greater disruption of sarcoplasmic reticulum and mitochondrial membranes and the degradation and release of structural proteins from the continuous connections of myofibrils and the sarcolemma.
A new Col1a1 conditional knock-in mouse model to study osteogenesis imperfecta
Authors: Dimori Milena , Toulany Mahtab , Sultana Lira Samia , Onal Melda , Thostenson Jeff D , Carroll John L , O’Brien Charles A , Morello Roy
Published: November 2024

Osteogenesis imperfecta (OI) constitutes a family of bone fragility disorders characterized by both genetic and clinical heterogeneity. Several different mouse models reproduce the classic features of OI, and the most commonly studied carry either a spontaneous or genetically induced pathogenic variant in the Col1a1 or Col1a2 gene. When OI is caused by primary alterations of type I collagen, it represents a systemic connective tissue disease that, in addition to the skeleton, also affects several extra-skeletal tissues and organs, such as skin, teeth, lung, heart, and others, where the altered type I collagen is also expressed. Currently, existing mouse models harbor a disease-causing genetic variant in all tissues and do not allow assessing the primary vs secondary consequences of the mutation on a specific organ/system. Here, we describe the generation of the first conditional knock-in allele for Col1a1 that can express a severe OI-causing glycine substitution (p.Gly1146Arg) in the triple helical region of α1(I) but only after Cre-driven recombination in the tissue of choice. We called this new dominant allele Col1a1G1146R-Floxed/+ and introduced it into the murine model. We describe its validation by crossing mice carrying this allele with EIIA-Cre expressing mice and showing that offspring with the recombined allele reproduce the classic features of a severe form of OI. The new mouse model will be useful to study the tissue-specific impact of this severe mutation on organs, such as the lung, the heart, and others.
The role of vitamin D metabolism in regulating bone turnover in adolescents with perinatally-acquired HIV in Southern Africa: a cross-sectional study in Zimbabwe and Zambia
Authors: Madanhire Tafadzwa , Ward Kate A , Macdougall Amy , Mohammed Nuredin , Filteau Suzanne , Kasonka Lackson , Mabuda Hilda B , Chisenga Molly , Tang Jonathan , Fraser William D , Bandason Tsitsi , Dzavakwa Nyasha V , Simms Victoria , Ferrand Rashida A , Gregson Celia L
Published: November 2024

Vitamin D dysregulation can occur in people living with HIV, disrupting calcium homeostasis, and bone turnover. We aimed to investigate the potential mechanisms by which vitamin D regulates bone turnover in adolescents living with perinatally-acquired HIV (ALWH) in Southern Africa. A pre-planned secondary analysis was performed of baseline data from the vitamin D for adolescents with HIV to reduce musculoskeletal morbidity and immunopathology trial (PACTR20200989766029) which enrolled ALWH (11–19 yr) taking antiretroviral therapy for ≥6 mo, and recorded socio-demographic, clinical and dietary data. After over-night fasting, vitamin D metabolites (25(OH)D, 1,25(OH)2D, and 24,25(OH)2D), intact parathyroid hormone (PTH), and bone turnover markers (BTMs) (C-terminal telopeptide of type I collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP)) were measured. Tandem Mass Spectrometry measured vitamin D metabolites, while intact PTH and BTMs were analyzed by electrochemiluminescence immunoassay. Stratified by 25(OH)D (<75 vs ≥75 nmol/L), associations between standardized concentrations (β = standard deviations) of vitamin D metabolites, intact PTH and BTMs were assessed using structural equations modelling (SEM) adjusted for age, sex, and country (Zimbabwe/Zambia). Among the 842 ALWH enrolled, the median dietary calcium intake was 100 mg (IQR: 55–145). The SEM showed PTH was positively associated (β: 0.21; 95% CI, 0.1, 0.32) with 1,25(OH)2D, only when 25(OH)D was <75 vs ≥75 nmol/L (β: 0.23; 95%CI, −0.13, 0.59), with evidence of an interaction (β: −0.11; 95%CI, −0.20, −0.02). A positive relationship between 25(OH)D and 24,25(OH)2D was seen irrespective of 25(OH)D concentration. 24,25(OH)2D was inversely related to BTMs, particularly when 25(OH)D was <75 nmol/L (CTX: β: −0.15; 95% CI, −0.24, −0.06 and P1NP: β: −0.14; 95%CI, −0.22, −0.06). There was interaction between dietary calcium and 25(OH)D on PTH (β: −0.15; 95% CI, −0.22, −0.07) suggesting an interaction between low 25(OH)D and low dietary calcium which increases PTH. In conclusion, associations between 25(OH)D, PTH, 1,25(OH)2D, and BTMs in ALWH appear dependent upon 25(OH)D concentrations <75 nmol/L and calcium intake. A novel, potentially causal pathway between 25(OH)D, 24,25(OH)2D, and BTMs was seen. Findings enhance understanding of vitamin D metabolism in people living with HIV.
Assessing the potential spread of Zaprionus tuberculatus (Diptera: Drosophilidae) in the Americas: insights for proactive management and agricultural protection
Authors: Viana José Pedro Cavalcante , Viana Matheus Cavalcante , Cavalcanti Fábio André Gomes Silva , Mateus Rogério Pincela , Bitner-Mathé Blanche Christine , Garcia Flávio Roberto Mello , Jobim Karina , Madi-Ravazzi Lilian , Rohde Claudia , Martins Marlucia Bonifácio , Tidon Rosana
Published: November 2024

Invasive species pose significant ecological and economic threats globally. Zaprionus tuberculatus Malloch, a drosophilid fruit fly native to the Afrotropical region and Indian Ocean islands, is included in the pest list of the Center for Agriculture and Bioscience (CABI) because it uses fruit as breeding sites and can damage cultivated areas. This fly species extended its range across Europe in the late 20th century; in 2020, it was recorded in South America, and currently, it is widely distributed in Brazil. Here, we assess the potential spreading of Zaprionus tuberculatus in Central and North America based on 2 distinct origins of propagules: from South America and from Europe. To this end, we developed species distribution models using bioclimatic variables and elevation data to project potentially suitable habitats and infer invasion routes. In any case, our results indicate suitability for Z. tuberculatus colonization in Central and North America, including major fruit-producing areas in Central American countries and the United States (Florida and California). The rapid dispersal ability of Z. tuberculatus, coupled with its adaptability to diverse environments, underscores the urgency for proactive monitoring and control measures. Therefore, this study provides valuable insights for developing proactive measures to mitigate the spread of Z. tuberculatus and protect agricultural productivity in the Americas.
Direct and indirect effects of selective insecticides on 2 generalist predators of Bemisia tabaci (Hemiptera: Aleyrodidae)
Authors: Parkins Albertha J , Kheirodin Arash , Perier Jermaine D , Cremonez Paulo S G , Riley David G , Simmons Alvin M , Schmidt Jason M
Published: November 2024

Generalist arthropod predators have historically contributed to the suppression of arthropod pests in many agroecosystems. The successful implementation of integrated pest management (IPM) programs hinges on the incorporation of insecticides that are compatible with the biological attributes of natural enemies of pests. A potentially promising pathway is improving biological control by natural enemies through the timely application of selective insecticides. In our study, adult predators were exposed to commercially available insecticides (cyantraniliprole and pyriproxyfen) using a combined laboratory and field approach to assess their effects on survivorship and predation. We isolated 2 predators, Hippodamia convergens Guérin-Méneville and Geocoris punctipes (Say), in the laboratory to estimate the survivorship and consumption of whitefly nymphs, Bemisia tabaci (Gennadius). In the field, we deployed whitefly nymph-infested potted cotton plants in replicated cotton plots with both insecticide treatments. We enumerated whitefly nymph populations on enclosed (predator-exclusion) and open (predator-accessible) potted plants. While pyriproxyfen had a negligible effect on the predators, cyantraniliprole exposure directly affected H. convergence by reducing survivorship duration and indirectly influenced both predators by reducing prey consumption and altering the consumption of alternative prey. In field conditions, regardless of pesticide exposure, whitefly-infested potted plants that excluded predators had more whiteflies than predator-accessible potted plants. Overall, pyriproxyfen demonstrated minimal impact on the predators in the laboratory or field, while cyantraniliprole adversely influenced mortality and indirect foraging under controlled laboratory conditions but did not have a significant impact in the field.
Population records reveal expanded habitat preference for the endemic, predaceous Jamaican fungus gnat Neoditomyia farri (Diptera, Keroplatidae)
Authors: Stewart Ronald S , Kouwenberg Silvia , Pauel Johannes , Stellwagen Sarah
Published: November 2024

The predaceous fly Neoditomyia farri Coher is currently regarded as having an unknown population distribution in Jamaica. The larvae are known for their production of sticky “fishing lines” that are covered in adhesive droplets for prey capture and hang down from cave walls and ceilings. Published research beyond early observational records of the species is limited to one site—Dromilly Cave in the parish of Trelawny. The Jamaican Caves Organisation has observed larvae of the species at 26 caves visited over the last 2 decades and compiled a database with details of approximate numbers, internal and external environmental conditions, and accurate positions. Based on these records, we present evidence that the species is not cave obligate and describe factors that may suggest potential additional sites where the species can be found. Taken together, our observations paint a picture of a species which is ubiquitous and not under discernible threat, making it an excellent candidate for further research on its unique life history and behavior, which remain poorly understood.
Challenges in the Vespertilionidae phylogeny: resolving Pipistrellus nathusii placement and affirming generic status for Asian pipistrelles
Authors: Dool Serena E , Puechmaille Sébastien J
Published: November 2024

Vespertilionidae is a species-rich family of bats that experienced rapid diversification events and contains many morphologically conserved taxa, resulting in challenges to taxonomic and phylogenetic resolution for members of this family. One example of a challenging group is the pipistrelles, which several studies have recovered as paraphyletic. Pipistrellus nathusii is noteworthy for being recovered either as sister to other European Pipistrellus species, more closely related to Nyctalus, or sister to the clade comprising Nyctalus and European Pipistrellus species. Using a core data set of 6 nuclear introns, and an extended data set of 10 nuclear introns, we employ multiple independent phylogenetic methods that are robust in the presence of incomplete lineage sorting or hybridization to resolve the placement of P. nathusii. In addition, our data confirm the distinction of the Asian Pipistrelle taxa which form a distinct genus sister to the clade comprising Vansonia, Pipistrellus, and Nyctalus.
Elevated risk of lung cancer among Asian American women who have never smoked: an emerging cancer disparity
Authors: Gomez Scarlett Lin , DeRouen Mindy , Chen Jr Moon S , Wakelee Heather , Velotta Jeffrey B , Sakoda Lori C , Shariff-Marco Salma , Reynolds Peggy , Cheng Iona
Published: November 2024

Lung cancer is a leading cause of cancer mortality for most ethnic groups of Asian American women, including Chinese, Korean, Japanese, and Vietnamese Americans, a striking pattern given the exceedingly low prevalence of smoking among Asian American women in the general population. Recent research demonstrates that among Asian American women with a lung cancer diagnosis, the vast majority of patients have never smoked, a rate as high as 80% among Chinese and Asian Indian American women. Despite declining rates in lung cancer overall in the United States, rates among Asian American women who have never smoked appear to be increasing. This commentary articulates extant knowledge, based on studies in Asia, of a range of risk factors, such as a family history of lung cancer; a history of lung diseases, including tuberculosis and chronic obstructive pulmonary disease; exposure to cooking fumes and second-hand smoke; and various putative risk factors. Unique mutational profiles at the tumor level, including a higher prevalence of EGFR variations among Asian populations, highlight the importance of tumor genomic testing of newly diagnosed patients. Additional research is essential, given the high burden of disease among Asian American women who have never smoked and the limited knowledge regarding contributing risk factors specific to Asian American women, because the risk factors identified in Asian people living in Asia may not apply.
Potential of the pharmacological inhibition of CCL2-CCR2 axis via targeting FROUNT to prevent the initiation and the progression of intracranial aneurysms in rats
Authors: Ono Isao , Itani Masahiko , Okada Akihiro , Kawashima Akitsugu , Toda Etsuko , Arakawa Yoshiki , Terashima Yuya , Aoki Tomohiro
Published: November 2024

Intracranial aneurysms (IAs) affect 1%-5% of the public and are a major cause of subarachnoid hemorrhage. Currently, there is no medical treatment to prevent the progression or rupture of IAs. Recent studies have defined IA as a chronic inflammatory disease in which macrophages infiltrate intracranial arteries via the CCL2-CCR2 axis. The chemokine signal regulator FROUNT mediates this axis, and it can be inhibited by the anti-alcoholism drug disulfiram. Therefore, inhibition of macrophage infiltration by interfering with FROUNT using disulfiram may represent a strategy to prevent exacerbation of IAs. Here, effects of disulfiram were investigated in vitro and in an animal model of IAs. FROUNT expression was observed on infiltrated macrophages both in human IAs and in the rat IA model by immunohistochemistry. In vitro treatment with disulfiram suppressed CCL2-mediated migration of cultured rat macrophages in a transwell system. Disulfiram administered in a rat model of IAs inhibited both the initiation and the enlargement of IAs in a dose-dependent manner; this was accompanied by suppression of macrophage infiltration. These results suggest that pharmacological inhibition of the CCL2-CCR2-FROUNT signaling cascade could be a treatment of patients with IAs.
Use model averaging instead of model selection in pulsar timing
Authors: van Haasteren Rutger
Published: November 2024

Over the past decade and a half, adoption of Bayesian inference in pulsar timing analysis has led to increasingly sophisticated models. The recent announcement of evidence for a stochastic background of gravitational waves by various pulsar timing array (PTA) projects highlighted Bayesian inference as a central tool for parameter estimation and model selection. Despite its success, Bayesian inference is occasionally misused in the pulsar timing community. A common workflow is that the data is analysed in multiple steps: a first analysis of single pulsars individually, and a subsequent analysis of the whole array of pulsars. A mistake that is then sometimes introduced stems from using the posterior distribution to craft the prior for the analysis of the same data in a second step, a practice referred to in the statistics literature as ‘circular analysis’. This is done to prune the model for computational efficiency. Multiple recent high-profile searches for gravitational waves by PTA projects have this workflow. This letter highlights this error and suggests that Spike and Slab priors can be used to carry out model averaging instead of model selection in a single pass. Spike and Slab priors are proved to be equal to log-uniform priors.
Linking the transcriptome to physiology: response of the proteome of Cupriavidus metallidurans to changing metal availability
Authors: Galea Diana , Herzberg Martin , Dobritzsch Dirk , Fuszard Matt , Nies Dietrich H
Published: November 2024

Cupriavidus metallidurans CH34 is a metal-resistant bacterium. Its metal homeostasis is based on a flow equilibrium of metal ion uptake and efflux reactions, which adapts to changing metal concentrations within an hour. At high metal concentrations, upregulation of the genes for metal efflux systems occurs within minutes. Here, we investigate the changes in the bacterial proteome accompanying these genetic and physiological events after 1.5 cell duplications, which took 3 h. To that end, C. metallidurans CH34 and its plasmid-free derivative, AE104, either were challenged with a toxic metal mix or were cultivated under metal-starvation conditions, followed by bottom-up proteomics. When metal-shocked or -starved cells were compared with their respective controls, 3540 proteins changed in abundance, with 76% appearing in one, but not the other, condition; the remaining 24% were up- or downregulated. Metal-shocked C. metallidurans strains had adjusted their proteomes to combat metal stress. The most prominent polypeptides were the products of the plasmid-encoded metal-resistance determinants in strain CH34, particularly the CzcCBA transenvelope efflux system. Moreover, the influence of antisense transcripts on the proteome was also revealed. In one specific example, the impact of an asRNA on the abundance of gene products could be demonstrated and this yielded new insights into the function of the transmembrane efflux complex ZniCBA under conditions of metal starvation.
Mercury records from natural archives reveal ecosystem responses to changing atmospheric deposition
Authors: Chen Qinqin , Wu Qingru , Cui Yuying , Wang Shuxiao
Published: November 2024

Global ecosystems face mercury contamination, yet long-term data are scarce, hindering understanding of ecosystem responses to atmospheric Hg input changes. To bridge the data gap and assess ecosystem responses, we compiled and compared a mercury accumulation database from peat, lake, ice and marine deposits worldwide with atmospheric mercury deposition modelled by GEOS-Chem, focusing on trends, magnitudes, spatial–temporal distributions and impact factors. The mercury fluxes in all four deposits showed a 5- to 9-fold increase over 1700–2012, with lake and peat mercury fluxes that generally mirrored atmospheric deposition trends. Significant decreases in lake and peat mercury fluxes post-1950 in Europe evidenced effective environmental policies, whereas rises in East Asia, Africa and Oceania highlighted coal-use impacts, inter alia. Conversely, mercury fluxes in marine and high-altitude ecosystems did not align well with atmospheric deposition, emphasizing natural influences over anthropogenic impacts. Our study underscores the importance of these key regions and ecosystems for future mercury management.
Development of a City-wide Rapid Antiretroviral Therapy Initiation Toolkit for People Newly Diagnosed With HIV in the Southern United States
Authors: Pettit A C , Ahonkhai A A , Pierce L , Rebeiro P F , Valdebenito C M , Woods J , Gregory L , Walton C , Nash R , Summers N A , Van Wylen A , Thompson D , Hayes-Winton M , Eke A , Pichon L C , Audet C M
Published: November 2024

Background

Rapid antiretroviral therapy (ART) initiation, in which individuals with HIV start treatment within days of diagnosis, is a key component of the United States (US) Ending the HIV Epidemic initiative. The Memphis Metropolitan Statistical Area ranks second in the US for HIV incidence, yet only ∼60% of individuals link to treatment within 1 month of diagnosis. This study aimed to identify barriers and strategies for implementing rapid ART initiation in Memphis.

Methods

From August to December 2022, we conducted process mapping guided by the Consolidated Framework for Implementation Research to outline the steps from 3 HIV testing sites to ART prescription at 3 Ryan White-funded clinics in Memphis, Tennessee. We used modified conjoint analyses to prioritize barriers and identify strategies for improving rapid ART implementation, focusing on the importance and feasibility of changes.

Findings

Prioritized barriers included intersectional stigma and a lack of access to centralized information about the rapid ART program, branding and logo development, inter- and intra-organizational networking and communication, testing and treatment resources (HIV testing kits and ART starter packs), rapid ART knowledge, and organizational champions. Strategies to address these barriers were compiled into a local rapid ART toolkit.

Conclusions

We identified modifiable systemic barriers to rapid ART initiation in Memphis, a community disproportionately affected by HIV. The strategies developed to address these barriers informed the creation of a locally relevant rapid ART toolkit for future evaluation. These methods could be applied in other high-burden areas seeking to develop local rapid ART models.
Bizarre intravascular leiomyoma with intracardiac extension starting in the ovarian vein: a case report from Syria
Authors: Babi Amal , Shebli Baraa , Ghabally Mike , Alkanj Hussein
Published: November 2024

Intravascular leiomyoma (IVL) with intracardiac extension (ICE) represents an exceedingly rare diagnosis of a cardiac mass. We present the case of a 42-year-old woman with recurrent syncopal episodes. Cardiac investigations revealed an extensive, mobile mass stretching from the inferior vena cava (IVC) through the right heart to the bifurcation of the pulmonary artery. Emergent surgery was conducted to excise the mass. Post-operative assessment indicated a potential malignancy in the adnexa. A subsequent surgery to resect the uterus with the adnexa, the primary origin of the mass, confirmed the diagnosis of IVL with ICE. The initial diagnostic ambiguity and the urgent pulmonary artery involvement necessitated a two-step surgical approach. Despite the propensity for recurrence, a 5-year follow-up remained unremarkable. This case underscores the importance of considering IVL with ICE in the differential diagnosis, which can expedite both diagnosis and treatment.
Transfusion related babesiosis in a non-endemic region (Western New York)
Authors: Aladeen Joseph , Wadhawan Pranav , Pendyala Reshub , Bajwa Bikram , Bajwa Rajinder P
Published: November 2024

Babesiosis, an emerging tick-borne zoonosis caused by parasites of the genus Babesia, is typically transmitted via the black-legged tick. Occasionally, Babesia can also be transmitted through red blood cell transfusion. In this report, we present a case of babesiosis resulting from a red blood cell transfusion in an area where the pathogen is not endemic. The patient presented with a high-grade fever and hemolytic anemia. This case underscores the critical importance of recognizing Babesia as a cause of hemolysis and emphasizes the necessity of implementing universal screening of blood products for Babesia. Enhanced vigilance in blood safety protocols is imperative to prevent transfusion-associated babesiosis.
Real-world effectiveness and prognostic factors of durvalumab plus chemotherapy in a multicentric cohort with advanced biliary tract cancer
Authors: Huang Wen-Kuan , Tang Yan-Jei , Wu Chiao-En , Hou Ming-Mo , Hsu Hung-Chih , Su Po-Jung , Chiang Nai-Jung , Chen San-Chi , Yeh Chun-Nan , Chen Jen-Shi , Chen Ming-Huang , Hsieh Chia-Hsun , Chou Wen-Chi
Published: November 2024

Background

Biliary tract cancer (BTC) is an aggressive biliary tract cancer, arising from the bile ducts and gallbladder, with a poor prognosis. The TOPAZ-1 trial of durvalumab plus first-line chemotherapy (gemcitabine plus cisplatin) showed improved survival vs chemotherapy alone. This real-world study aimed to confirm the effectiveness of this regimen.

Methods

This retrospective, multicenter study included patients with advanced BTC treated with first-line durvalumab plus platinum chemotherapy at the Linkou, Taoyuan, and Tucheng branches of Chang Gung Memorial Hospital as well as at Taipei Veterans General Hospital between August 2021 and June 2023.

Results

Among the 45 patients with advanced biliary tree cancer treated with durvalumab plus cisplatin and gemcitabine as first-line treatment, the objective response rate was 31.1% (14 partial responses). An additional 40% (18 patients) had stable disease. The median progression-free survival was 5.6 months (95%CI, 4.4-6.9) and median overall survival was 15.8 months (95%CI, 7.9-23.8). Responders had significantly longer survival than non-responders (15.8 vs 3.3 months). Although higher durvalumab doses (1000-1500 mg) appeared to have improved efficacy compared to lower doses (<1000 mg), the difference was not statistically significant. On multivariate analysis, poor ECOG performance status (≥2) and a high neutrophil-lymphocyte ratio were independent prognostic factors for shorter overall survival.

Conclusion

This real-world study demonstrated the comparable efficacy of durvalumab plus chemotherapy to the TOPAZ-1 trial for patients with advanced BTC and identified prognostic factors. There was a trend toward improved efficacy with higher durvalumab dosing (1000-1500 mg) vs lower dosing, though further research is needed to confirm this relationship.
Management of severe immune-related adverse events and outcomes in patients with advanced non-small cell lung cancer receiving immune checkpoint inhibitors
Authors: Naidoo Jarushka , Johnson Douglas B , Doran Charlotte , Wang Yuexi , Zhang Yan , Le Trong Kim , Hopson Sari , Dreyfus Brian , Lal Lincy S , Vyas Charmy , Goldstein Shay , Izadi Zara
Published: November 2024

Background

Immune checkpoint inhibitors (ICIs) are associated with severe immune-related adverse events (s-irAEs) that result in hospitalization, emergency department (ED) visits, treatment discontinuation, or death. This study examined the impact of s-irAEs and their earliest management strategies on clinical outcomes in advanced non-small cell lung cancer (NSCLC).

Methods

Data were derived from ConcertAI Patient360 NSCLC, a US-based electronic medical record database, between January 2012 and May 2021. Eligible patients had advanced NSCLC and received ICI-containing therapy. s-irAEs and management actions were abstracted from unstructured EHR data from ICI initiation through the earliest of 100 days after ICI discontinuation, start of a non-ICI-containing regimen, loss to follow up, end of study period, or death. Multivariable Cox regression analysis was used to evaluate the association between s-irAEs and their earliest management strategies, and real-world progression-free survival (rwPFS) and real-world overall survival (rwOS).

Results

The study included 3211 patients. Median (IQR) age was 67 (60-73) years, and 44.9% were female. Most patients (61.6%) initiated ICIs as first-line therapy; half (50.1%) initiated ICIs as monotherapy, with nivolumab monotherapy (29.5%) as the most common initial ICI-containing regimen in any line. Overall, 8.6% of patients experienced s-irAEs, most often diarrhea (3.5%), pneumonitis (1.4%), and rash (1.3%). Among patients who experienced at least one s-irAEs, over half (57.4%) were hospitalized, and 71.8% were treated with corticosteroids, any time after the occurrence of their first s-irAEs. Median rwPFS was 4.9 (95%CI, 4.6-5.2) months, and median rwOS was 13.6 (12.6-14.7) months from ICI initiation. rwPFS and rwOS were comparable between patients with s-irAEs vs patients without s-irAEs when s-irAEs were first managed with anti-cancer treatment interruptions. Patients with s-irAEs had a 53% (22.3%-91.4%) higher risk of death than patients without s-irAEs when s-irAEs initially required corticosteroids or other immunosuppressants, and a 61% (37.9%-87.9%) higher risk of death when s-irAEs first required hospitalization or ED admission.

Conclusion

The impact of s-irAEs on clinical outcomes may depend on the initial intervention required to manage the adverse event. s-irAEs were associated with worse outcomes when they initially required hospital/ED admission, corticosteroids, or other immunosuppression.
The German Bible from Martin Luther to Johann Eck
Authors: Leppin Volker
Published: November 2024

The Middle Ages provided German-speaking readers with a good number of vernacular translations. All of them followed the Vulgate with the exception of Luther’s which took Erasmus’s Greek New Testament as a basis for what would become his tremendously successful translation of the New Testament. The Scripture principle and the idea of the priesthood of all baptized together formed the Reformation’s impulse in translating the Bible. Even Catholic authors could not ignore joining in the success of the Bible in the vernacular. Jerome Emser edited a translation of the New Testament in 1527 meant to replace Luther’s version with a Catholic one, which nonetheless followed Luther’s translation almost completely, even as Emser raised some issues about alleged dogmatic prejudices staining Luther’s efforts. In the end, the history of German Bible translations in the Reformation era is a story that revolves around the Luther Bible.
Reformation Children’s Bibles from Martin Luther to Wendelin Rihel
Authors: Keuchen Marion
Published: November 2024

Through the Reformation, the Bible and education gained central importance. The Reformation principle that the Bible as Holy Scripture should be the only basis and norm for faith (sola Scriptura) emphasized the importance of reading and writing. The Reformers wanted children and laypeople to become independent church members. Teaching material was needed for school lessons, and study Bibles with pictures were produced; Martin Luther’s Little Prayer Book (1529) served as a prototype. The Lay Bible (1540) by Wendelin Rihel was a continuation of Luther’s Little Prayer Book. This innovative period laid the foundation for later children’s Bible traditions.
The Medieval Four Senses of Scripture and Nicholas of Lyra’s Literal Interpretation of the Bible
Authors: Smith Lesley
Published: November 2024

This chapter seeks to show that many of the characteristics associated with Reformation biblical interpretation can already be found in the exegesis of the fourteenth-century Franciscan scholar Nicholas of Lyra (d. 1349), said to be Martin Luther’s favorite exegete. Nicholas’s vast biblical commentary, Postilla litteralis super totam bibliam (1322–31), with its shorter companion, the Postilla moralis (1333–39), was enormously popular, surviving even today in hundreds of manuscripts. Commonly comparing Christian and Jewish understanding of the same text (including through a set of comparative exegetical drawings, especially for Exodus and Ezekiel), Nicholas almost always comes down on the side of the Jewish interpretation as being superior to the Christian. Nevertheless, this does not alter his view of the fundamental wrongness of the Jewish understanding of God’s word.
Reformers and the Biblia Hebraica
Authors: Graves Michael
Published: November 2024

Christian Hebraism in this era arose out of Renaissance humanistic scholarship and Christian interest in Jewish mysticism. As the Protestant Reformation took shape, Protestants devoted significant attention to the Biblia Hebraica as part of their emphasis on scriptural authority. New translations were made into Latin and vernacular languages based on the Hebrew, and biblical commentaries offered fresh exegesis of the Old Testament that combined rabbinic learning, historical interest, and Christian theological interpretation. Important Protestant Bibles include Sebastian Münster’s Latin Biblia Hebraica, Luther’s German Bible, Pierre Olivétan’s French Bible, and the King James Version. Influential Protestant commentators on the Hebrew Bible include Johannes Oecolampadius, Martin Bucer, John Calvin, and Johannes Drusius. Through Protestant–Catholic debates over the reliability of the Masoretic Bible, Hebrew textual criticism emerged as a field of study. Eventually, Protestant Hebrew scholarship became less defined by doctrinal distinctives and focused more on text-critical investigations.
Martin Luther’s Biblical Hermeneutics
Authors: Brown Christopher Boyd
Published: November 2024

Martin Luther’s Reformation “breakthrough” centered on a new approach to understanding the Bible which he unfolded throughout his subsequent career. Insisting on the distinction between God’s “two sermons” of Law and Gospel and on the centrality of Christ as Savior throughout the biblical canon, Luther upheld Scripture as the sole judge of Christian teaching and encouraged the study of the original Hebrew and Greek texts. Against the “Enthusiasts,” Luther identified this external Word in all its forms not simply as the authoritative description of God’s action but as the sole means through which the Holy Spirit was active among human beings to create faith. In his theological treatises, lectures, sermons, and especially in his annotated German translation of the Bible, as well as in his catechism, hymns, and their accompanying art, Luther applied and exemplified his hermeneutical approach for other readers and interpreters of Scripture, theologians, and laity alike.
The Authority and Interpretation of the Bible by Huldrych Zwingli and the Zürich Reformation
Authors: Opitz Peter
Published: November 2024

The first establishment of the church on the basis of sola Scriptura in the Reformation period took place in Zurich in 1523. The theological ground was provided by the Zurich reformer Huldrych Zwingli. On the one hand, Zwingli interpreted the Bible with the best humanistic methods of his time. On the other hand, he taught that only the Holy Spirit can bring about the proper understanding of the Bible. The Spirit that spoke to the people in the Bible also speaks to its readers today. Because of the exclusive supremacy of God’s Word, all interpretations of the Bible must be further examined according to Christ, the living Word of God in human form. The accuracy of interpretations remains relative. The divine truth is ultimately in God’s hands. Zwingli and his teaching laid the foundation for the entire Reformed tradition.
Biblical Authority and the Radical Reformation
Authors: Hamilton Alastair
Published: November 2024

The emphasis on mysticism and personal inspiration became particularly prominent in circles connected with the Radical Reformation. During a time of spiritual and political turmoil, with its quick changes of the official religion, radical reform emphasized the interiorization of religious piety, at times to the abandonment of the authority of the visible churches as well as to a demotion of the Bible’s unique role as inspired. The work of the same Holy Spirit that had inspired the Evangelists could be detected in other writings, including the biblical apocrypha and extra-biblical works of piety such as the Imitation of Christ and the Theologia Germanica. In the end, Nicodemism became an increasingly common feature of the period, entailing outward conformity, the readiness to attend the religious services of any church chosen by the state, while the individual could retain an inner religious conviction that transcended ceremonial and liturgical differences.
Thomas de Vio Cajetan (1469–1534)
Authors: Arnold Claus
Published: November 2024

Although a papalist and a Thomist who opposed Luther in 1518, Tommaso de Vio (Cardinal Cajetan) proposed later in his life a type of biblical hermeneutics which was less inspired by Counter-Reformation than by a humanist textual criticism and a strict orientation towards the literal sense of Scripture. Cajetan’s criticism of the Vulgate, of traditional patristic exegesis, and of ecclesiastical precepts not founded on the literal meaning of Scripture found a direct, if not explicit, rejection by the Council of Trent. But ultimately his exegetical works escaped censuring and expurgation. In 1639, the Spanish Dominicans of Alcala, seat of the famous Universitas Complutense, decided to republish Cajetan’s commentaries in five volumes at Lyons, outside the reach of the Spanish Inquisition. In the form of the Alcala opera omnia, Cajetan’s exegesis continued to exert influence in Catholicism and beyond well into the twentieth century.
Heinrich Bullinger (1504–1575)
Authors: Giselbrecht Rebecca A.
Published: November 2024

Heinrich Bullinger (1504–75) discovered the Bible as a young man and this discovery resulted in a lifelong intensive working with and from the Bible in his pastoral, homiletical, and theological work. His theology of the covenant was a leading hermeneutical principle in his work. The scriptural principle, schrift prinzip, that Scripture interprets Scripture, also defined and determined Bullinger’s hermeneutic and exegetical work. The reformer cared for the spiritual needs of his congregation and influenced the world with practical pastoral theological wisdom rooted in scriptural warrant and prayer. Bullinger understood the Bible as the truth, meaning that the word of God defines reality and testifies to Christ the witness, who attests to the presence of God in our lives.
Roman Catholicism and the Biblical Canon
Authors: Murray Luke
Published: November 2024

What was the position of the Catholic Church on the canon of Scripture during the Reformation and early modern era? How did Catholics respond to Luther’s decision to exclude certain books from his German Bible? This essay will examine the influence of Jerome, Augustine, and early councils on the question as well as the views prominent Catholics such as Cajetan, Cisneros, and Erasmus. With the rise of Luther and the reformers’ rejection of the “deuterocanonicals,” the essay will also examine the response of five early modern Catholic apologists on the issue: Johann Cochlaeus (1479–1552), Johann Eck (1486–1543), Johann Dietenberger (1475–1537), Alfonso de Castro (1495–1558), and Johannes Driedo (c.1480–1535). The article will then conclude by looking at Trent’s response and how Catholics understood the issue after the council by briefly examining Sixtus of Sienna (1520–69) and Cornelius a Lapide’s (1567–1637) comments on the question.
The Eucharist (John 6; 1 Cor. 10–11)
Authors: Nelson Burnett Amy
Published: November 2024

From the beginning of the eucharistic controversy, Luther and the Swiss reformers disagreed on whether John 6:63 was relevant to the Lord’s Supper, whether “this is my body” should be interpreted literally or figuratively, and whether 1 Cor. 10:16 referred to the fellowship among Christians or the distribution of Christ’s body in the bread. Martin Bucer advocated an alternative position that used John 6:53–58 and 1 Cor. 10:16 to highlight the believer’s spiritual reception of Christ’s true body. This allowed agreement with Melanchthon and made possible the 1536 Wittenberg Concord. While Calvin was initially influenced by Bucer’s exegesis, Bullinger remained loyal to Zwingli’s interpretation, and his position influenced the major Reformed confessions.