bluuebunny/crossref_metadata_2025 huggingface dataset:
Barriers to research in family medicine—interviews with Portuguese family physician researchers
Authors: Gil Conde Margarida , Rodrigues Vera L , Ramos Raquel C , Rente Ana , Broeiro-Gonçalves Paula , Ribeiro Cristina , Nicola Paulo J
Published: February 2024

Background

There is a need for a deeper understanding of the barriers to research in family medicine (FM) and to consider the perceptions and perspectives of professionals. Our study aims to provide a strategic view for research capacity building in FM. We included the perspective of family physician researchers (FPR) on the existing barriers to investigation in this context.

Objectives

To understand and characterize the barriers to research in FM (personal and structural), from the perspective of Portuguese family physicians who are researchers.

Methods

A qualitative study, of phenomenological nature, was performed, through the conduction of semi-structured interviews with FPR, from 2019 to 2022. Data analysis and thematic coding were done on MAxQDA®, with inductive and deductive approaches, until data saturation was reached.

Results

A total of 12 family physicians/researchers were interviewed. Seven main themes were identified as barriers to research: time, professional valorization, funding, ethics committees, infrastructure, management/institutions, and participants. Each theme is divided into subthemes that make it possible to assess how a barrier can affect researchers in performing research activities.

Conclusion

Our study highlights the identification of 7 main barriers. Structuring them into sub-themes not only improved the organization of our results but also provided robust support for the next phase, namely the application of a survey with the aim of gaining a deeper insight into the repercussions that these barriers to FPR have at a national level. This research is crucial to laying the foundations for a policy document that offers well-defined and tailored recommendations to address the barriers we have uncovered.
Excessive tubulin glutamylation leads to progressive cone-rod dystrophy and loss of outer segment integrity
Authors: Aljammal Rawaa , Saravanan Thamaraiselvi , Guan Tongju , Rhodes Scott , Robichaux Michael A , Ramamurthy Visvanathan
Published: February 2024

Mutations in Cytosolic Carboxypeptidase-like Protein 5 (CCP5) are associated with vision loss in humans. To decipher the mechanisms behind CCP5-associated blindness, we generated a novel mouse model lacking CCP5. In this model, we found that increased tubulin glutamylation led to progressive cone-rod dystrophy, with cones showing a more pronounced and earlier functional loss than rod photoreceptors. The observed functional reduction was not due to cell death, levels, or the mislocalization of major phototransduction proteins. Instead, the increased tubulin glutamylation caused shortened photoreceptor axonemes and the formation of numerous abnormal membranous whorls that disrupted the integrity of photoreceptor outer segments (OS). Ultimately, excessive tubulin glutamylation led to the progressive loss of photoreceptors, affecting cones more severely than rods. Our results highlight the importance of maintaining tubulin glutamylation for normal photoreceptor function. Furthermore, we demonstrate that murine cone photoreceptors are more sensitive to disrupted tubulin glutamylation levels than rods, suggesting an essential role for axoneme in the structural integrity of the cone outer segment. This study provides valuable insights into the mechanisms of photoreceptor diseases linked to excessive tubulin glutamylation.
Identification and characterization of two P450 enzymes from Citrus sinensis involved in TMTT and DMNT biosyntheses and Asian citrus psyllid defense
Authors: Sun Xueli , Hu Chunhua , Yi Ganjun , Zhang Xinxin
Published: February 2024

The homoterpenes (3E)-4,8-dimethyl-1,3,7-nonatriene (DMNT) and (E,E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene (TMTT) are the major herbivore-induced plant volatiles that help in defense directly by acting as repellants and indirectly by recruiting insects’ natural enemies. In this study, DMNT and TMTT were confirmed to be emitted from citrus (Citrus sinensis) leaves infested with Asian citrus psyllid (Diaphorina citri Kuwayama; ACP), and two cytochrome P450 (CYP) genes (CsCYP82L1 and CsCYP82L2) were newly identified and characterized. Understanding the functions of these genes in citrus defense will help plan strategies to manage huanglongbing caused by Candidatus Liberibacter asiaticus (CLas) and spread by ACP. Quantitative real-time PCR (qPCR) analysis showed that CsCYP82L1 and CsCYP82L2 were significantly upregulated in citrus leaves after ACP infestation. Yeast recombinant expression and enzyme assays indicated that CsCYP82L1 and CsCYP82L2 convert (E)-nerolidol to DMNT and (E,E)-geranyllinalool to TMTT. However, citrus calluses stably overexpressing CsCYP82L1 generated only DMNT, whereas those overexpressing CsCYP82L2 produced DMNT and TMTT. Furthermore, ACPs preferred wild-type lemon (Citrus limon) over the CsCYP82L1-overexpressing line in dual-choice feeding assays and mineral oil over TMTT or DMNT in behavioral bioassays. Finally, yeast one-hybrid, electrophoretic mobility shift, and dual luciferase assays demonstrated that CsERF017, an AP2/ERF transcription factor, directly bound to the CCGAC motif and activated CsCYP82L1. Moreover, the transient overexpression of CsERF017 in lemon leaves upregulated CsCYP82L1 in the absence and presence of ACP infestation. These results provide novel insights into homoterpene biosynthesis in C. sinensis and demonstrate the effect of homoterpenes on ACP behavior, laying a foundation to genetically manipulate homoterpene biosynthesis for application in huanglongbing and ACP control.
Bacterial infection in endometriosis: a silver-lining for the development of new non-hormonal therapy?
Authors: Khan Khaleque N , de Ziegler Dominique , Guo Sun-Wei
Published: February 2024

The pathogenesis of endometriosis is a hotly debated topic, yet still cloaked in multiple layers of hypothetical theories. A recent report raises the possibility that bacterial infection, especially those of the genus Fusobacterium, may be the cause of endometriosis, at least in certain women. More importantly, the demonstration that treatment with broad-spectrum antibiotics significantly reduced the size of lesions in a mouse endometriosis model rekindles the hope for new non-hormonal treatments. The development of new therapies has been plagued by strings of unsuccessful clinical trials over the last two decades. Is this antibiotic therapy, a silver lining for the research and development of non-hormonal drugs for endometriosis?
Assembling China’s Belt and Road Initiative: Discourse, Institution, and Materials
Authors: Hu Ran
Published: February 2024

The article uses the concept of assemblage to analyze the becoming, not being, of China’s Belt and Road Initiative (BRI), that is, the ways in which different elements were framed and constructed so as to constitute the BRI, often seen as China’s “grand” or “global” strategy. Different from rational and more-than-rational perspectives, the assemblage approach pays attention to the role of materials as well as the contingencies that were associated with the BRI. Thus, the article argues that the global BRI is best conceptualized as an assemblage that emerged through (de)territorializing processes in which various practices, institutions, discourses, and materials came together to form different relations with specific effects, rather than a set of principles simply conceived and imposed by China’s central government. The Chinese governmental institutions and national discourses are critical to its emergence, but so are materials such as the forms of policy papers and infrastructure. Seeing it this way allows us to understand how such a broad and heterogenous strategy as the BRI is held together without ceasing to be heterogenous; in other words, how the BRI emerges, travels, and mutates.
Coral mucus as a reservoir of bacteriophages targeting Vibrio pathogens
Authors: Rubio-Portillo Esther , Robertson Sophia , Antón Josefa
Published: February 2024

The increasing trend in sea surface temperature promotes the spread of Vibrio species, which are known to cause diseases in a wide range of marine organisms. Among these pathogens, Vibrio mediterranei has emerged as a significant threat, leading to bleaching in the coral species Oculina patagonica. Bacteriophages, or phages, are viruses that infect bacteria, thereby regulating microbial communities and playing a crucial role in the coral’s defense against pathogens. However, our understanding of phages that infect V. mediterranei is limited. In this study, we identified two phage species capable of infecting V. mediterranei by utilizing a combination of cultivation and metagenomic approaches. These phages are low-abundance specialists within the coral mucus layer that exhibit rapid proliferation in the presence of their hosts, suggesting a potential role in coral defense. Additionally, one of these phages possesses a conserved domain of a leucine-rich repeat protein, similar to those harbored in the coral genome, that plays a key role in pathogen recognition, hinting at potential coral–phage coevolution. Furthermore, our research suggests that lytic Vibrio infections could trigger prophage induction, which may disseminate genetic elements, including virulence factors, in the coral mucus layer. Overall, our findings underscore the importance of historical coral–phage interactions as a form of coral immunity against invasive Vibrio pathogens.
The Separability Thesis
Authors: Spoor Iris
Published: February 2024

Debates over the metaphysical status of aesthetic properties have persisted for decades in Aesthetics. One question that consistently arises in any discussion of aesthetic properties is whether they are fundamentally evaluative or descriptive in character. Aesthetic properties are often treated as parallel to moral properties which means many philosophers take it for granted that aesthetic properties are fundamentally evaluative. There are some philosophers, like Frank Sibley and Jerrold Levinson, who take the road less traveled and treat aesthetic properties as primarily descriptive in character. In this paper, I outline Levinson’s intriguing view that the evaluative aspect of an aesthetic property can be canceled leaving us with the descriptive essence of the property. I refer to this as the separability thesis. It contends that evaluative reactions to aesthetic properties can be separated from the objective, perceptual content of an aesthetic experience thereby leaving us with the non-evaluative core of the property. I go on to defend the separability thesis from a powerful challenge developed by Rafael De Clercq. Ultimately, I contend that while De Clercq’s argument is clever and insightful it fails to undermine the separability thesis.
In vitro activity of cefiderocol and comparator antibiotics against multidrug-resistant non-fermenting Gram-negative bacilli
Authors: Huang Yu-Shan , Chuang Yu-Chung , Chen Pao-Yu , Chou Pei-Chun , Wang Jann-Tay
Published: February 2024

Background

This study evaluated the in vitro activity of cefiderocol, ceftazidime/avibactam, and aztreonam/avibactam against clinically important multidrug-resistant non-fermenting Gram-negative bacilli.

Methods

Bacteraemic isolates of 126 multidrug-resistant Acinetobacter baumannii (MDRAB), 110 imipenem-resistant Pseudamoas aeruginosa [including 14 difficult-to-treat resistant P. aeruginosa (DTRPA)], 45 beta-lactam-non-susceptible Burkholderia cepacia complex (BCC), 47 levofloxacin or trimethoprim/sulfamethoxazole-non-susceptible Stenotrophomonas maltophilia and 22 ciprofloxacin-non-susceptible Elizabethkingia spp. collected between 2019 and 2021 were subjected to MIC determination for cefiderocol, ceftazidime/avibactam and aztreonam/avibactam.

Results

The MIC50/90s of ceﬁderocol for drug-resistant A. baumannii, P. aeruginosa, BCC, S. maltophilia and Elizabethkingia spp. were 0.25/2, 0.25/1, ≤0.06/≤0.06, ≤0.06/0.25 and >32/>32 mg/L, respectively. Cefiderocol inhibited 94.4% (119/126) of MDRAB, 100% of imipenem-resistant P. aeruginosa, 100% of DTRPA and 100% of BCC at an MIC ≤4 mg/L, and 97.9% (46/47) of S. maltophilia at ≤1 mg/L. Ceftazidime/avibactam inhibited 76.4% (84/110) of imipenem-resistant P. aeruginosa, 21.4% (3/14) of DTRPA and 68.9% (31/45) of BCC at an MIC ≤8 mg/L. Aztreonam/avibactam had MIC50/90s of 16/>32, 8/16 and 4/8 mg/L for imipenem-resistant P. aeruginosa, BCC and S. maltophilia, respectively. At ≤8 mg/L, aztreonam/avibactam inhibited 7.1% (1/14) of DTRPA and 93.6% (44/47) of S. maltophilia isolates. Elizabethkingia spp. demonstrated high MICs for cefiderocol, ceftazidime/avibactam and aztreonam/avibactam, with all MIC50s and MIC90s > 32 mg/L.

Conclusion

Cefiderocol may serve as an alternative treatment for multidrug-resistant A. baumannii, P. aeruginosa, BCC and S. maltophilia when other antibiotics have been ineffective or intolerable. The role of ceftazidime/avibactam and aztreonam/avibactam in the management of BCC or S. maltophilia infections warrants further investigation.
Effect of the initial pH of the culture medium on the nutrient consumption pattern of Bifidobacterium animalis subsp. lactis Bb12 and the improvement of acid resistance by purine and pyrimidine compounds
Authors: Zhang Zongcai , Yin Boxing , Liu Fei , Zhou Wei , Wang Mengrui , Chang Ziqing , Zhou Junping , Yue Mingzhe , Chen Junxia , Feng Zhen
Published: February 2024

Aims

During fermentation, the accumulation of acidic products can induce media acidification, which restrains the growth of Bifidobacterium animalis subsp. lactis Bb12 (Bb12). This study investigated the nutrient consumption patterns of Bb12 under acid stress and effects of specific nutrients on the acid resistance of Bb12.

Methods and results

Bb12 was cultured in chemically defined medium (CDM) at different initial pH values. Nutrient consumption patterns were analyzed in CDM at pH 5.3, 5.7, and 6.7. The patterns varied with pH: Asp + Asn had the highest consumption rate at pH 5.3 and 5.7, while Ala was predominant at pH 6.7. Regardless of the pH levels (5.3, 5.7, or 6.7), ascorbic acid, adenine, and Fe2+ were vitamins, nucleobases, and metal ions with the highest consumption rates, respectively. Nutrients whose consumption rates exceeded 50% were added individually in CDM at pH 5.3, 5.7, and 6.7. It was demonstrated that only some of them could promote the growth of Bb12. Mixed nutrients that could promote the growth of Bb12 were added to three different CDM. In CDM at pH 5.3, 5.7, and 6.7, it was found that the viable cell count of Bb12 was the highest after adding mixed nutrients, which were 8.87, 9.02, and 9.10 log CFU ml−1, respectively.

Conclusions

The findings suggest that the initial pH of the culture medium affects the nutrient consumption patterns of Bb12. Specific nutrients can enhance the growth of Bb12 under acidic conditions and increase its acid resistance.
Human technology intermediation to reduce cognitive load: understanding healthcare staff members’ practices to facilitate telehealth access in a Federally Qualified Health Center patient population
Authors: Williamson Alicia K , Antonio Marcy G , Davis Sage , Kameswaran Vaishnav , Dillahunt Tawanna R , Buis Lorraine R , Veinot Tiffany C
Published: February 2024

Objectives

The aim of this study was to investigate how healthcare staff intermediaries support Federally Qualified Health Center (FQHC) patients’ access to telehealth, how their approaches reflect cognitive load theory (CLT) and determine which approaches FQHC patients find helpful and whether their perceptions suggest cognitive load (CL) reduction.

Materials and Methods

Semistructured interviews with staff (n = 9) and patients (n = 22) at an FQHC in a Midwestern state. First-cycle coding of interview transcripts was performed inductively to identify helping processes and participants’ evaluations of them. Next, these inductive codes were mapped onto deductive codes from CLT.

Results

Staff intermediaries used 4 approaches to support access to, and usage of, video visits and patient portals for FQHC patients: (1) shielding patients from cognitive overload; (2) drawing from long-term memory; (3) supporting the development of schemas; and (4) reducing the extraneous load of negative emotions. These approaches could contribute to CL reduction and each was viewed as helpful to at least some patients. For patients, there were beneficial impacts on learning, emotions, and perceptions about the self and technology. Intermediation also resulted in successful visits despite challenges.

Discussion

Staff intermediaries made telehealth work for FQHC patients, and emotional support was crucial. Without prior training, staff discovered approaches that aligned with CLT and helped patients access technologies. Future healthcare intermediary interventions may benefit from the application of CLT in their design. Staff providing brief explanations about technical problems and solutions might help patients learn about technologies informally over time.

Conclusion

CLT can help with developing intermediary approaches for facilitating telehealth access.
Job search strategies and early careers of clinical informatics fellowship alumni (2016-2022)
Authors: Kim Ellen , Van Cain Melissa , Hron Jonathan D
Published: February 2024

Objective

To report on clinical informatics (CI) fellows’ job search and early careers.

Materials and Methods

In the summer of 2022, we performed a voluntary and anonymous survey of 242 known clinical informatics fellowship alumni from 2016 to 2022. The survey included questions about their initial job search process; first job, salary, and informatics time after training; and early career progression over the first 1-6 years after fellowship.

Results

Nearly half (101, 41.7%) responded to the survey. Median informatics time was 50%; most were compensated similar/better than a purely clinical position. Most reported CI fellowship significantly impacted their career, were satisfied with their first and current job after training, and provided advice for current fellows and CI education leaders. Graduates in 2022 had a median job search of 5 months, beginning 3-15 months before graduation; most had a position created for them. Nearly all graduates from 2016-2021 (61, 93.8%) had at least one change in roles/benefits since finishing training, with a trend for increased informatics time and salary.

Discussion

There was a wide variety of roles, salary, and funding sources for CI positions. This highlights some of the unique challenges CI fellows face and the importance of networking. These results will help CI education leaders, fellows, alumni, and prospective fellowship applicants.

Conclusion

Graduates felt that CI fellowship had a significant impact on their career, were pleased with their first jobs and early career trajectory. Continued follow-up of the experience of new graduates and alumni is needed to assess emerging patterns over time.
An open-source platform for pediatric cancer data exploration: a report from Data for the Common Good
Authors: Wyatt Kirk D , Graglia Luca , Furner Brian , Kang Bobae , Fitzsimons Michael , Grossman Robert L , Volchenboum Samuel L
Published: February 2024

Objective

The Pediatric Cancer Data Commons (PCDC)—a project of Data for the Common Good—houses clinical pediatric oncology data and utilizes the open-source Gen3 platform. To meet the needs of end users, the PCDC development team expanded the out-of-box functionality and developed additional custom features that should be useful to any group developing similar data commons.

Materials and Methods

Modifications of the PCDC data portal software were implemented to facilitate desired functionality.

Results

Newly developed functionality includes updates to authorization methods, expansion of filtering capabilities, and addition of data analysis functions.

Discussion

We describe the process by which custom functionalities were developed. Features are open source and available to be implemented and adapted to suit needs of data portals that utilize the Gen3 platform.

Conclusion

Data portals are indispensable tools for facilitating data sharing. Open-source infrastructure facilitates a modular and collaborative approach for meeting needs of end users and stakeholders.
smdi: an R package to perform structural missing data investigations on partially observed confounders in real-world evidence studies
Authors: Weberpals Janick , Raman Sudha R , Shaw Pamela A , Lee Hana , Hammill Bradley G , Toh Sengwee , Connolly John G , Dandreo Kimberly J , Tian Fang , Liu Wei , Li Jie , Hernández-Muñoz José J , Glynn Robert J , Desai Rishi J
Published: February 2024

Objectives

Partially observed confounder data pose a major challenge in statistical analyses aimed to inform causal inference using electronic health records (EHRs). While analytic approaches such as imputation are available, assumptions on underlying missingness patterns and mechanisms must be verified. We aimed to develop a toolkit to streamline missing data diagnostics to guide choice of analytic approaches based on meeting necessary assumptions.

Materials and methods

We developed the smdi (structural missing data investigations) R package based on results of a previous simulation study which considered structural assumptions of common missing data mechanisms in EHR.

Results

smdi enables users to run principled missing data investigations on partially observed confounders and implement functions to visualize, describe, and infer potential missingness patterns and mechanisms based on observed data.

Conclusions

The smdi R package is freely available on CRAN and can provide valuable insights into underlying missingness patterns and mechanisms and thereby help improve the robustness of real-world evidence studies.
Montenegro in the Works of Patrick Mac Swiney de Mashanaglass
Authors: Burzanović Slavko , Popović Olivera
Published: February 2024

This article analyzes texts about Montenegro of the Catholic Irish publicist Patrick Mac Swiney de Mashanaglass, who visited the country in 1899. He published two works about his experience and the information he collected: a travel account and a historical overview. The article discusses the motive for his arrival on the eastern Adriatic coast, the historical, political, and cultural context of this visit, and the factors that influenced the creation of a certain image of Montenegro in his works. Special attention is paid to the issues of the relationship between Montenegro and the Holy See, which Swiney analyzed from various standpoints, and which contributed to the growing interest in Catholic circles in the small Balkan principality. The key events in that sense were the signing and implementation of the Concordat between Montenegro and the Holy See, the first legal act of this type signed between the Vatican and an Orthodox country, and the political-religious problem that emerged around an institute in Rome dedicated to St Jerome.
Cultivation of recombinant Aspergillus niger strains on dairy whey as a carbohydrate source
Authors: Crament Teagan C , Arendsen Kayline , Rose Shaunita H , Jansen Trudy
Published: February 2024

Agricultural waste valorisation provides a sustainable solution to waste management, and combining waste utilisation with commodity production allows for responsible production processes. Recombinant Aspergillus niger D15 strains expressing fungal endoglucanases (Trichoderma reesei eg1 and eg2 and Aspergillus carneus aceg) were evaluated for their ability to utilise lactose as a carbon source to determine whether dairy waste could be used as a feedstock for enzyme production. The recombinant A. niger D15[eg1]PyrG, D15[eg2]PyrG, and D15[aceg]PyrG strains produced maximum endoglucanase activities of 34, 54, and 34 U/mL, respectively, on lactose and 23, 27, and 22 U/mL, respectively, on whey. The A. niger D15[eg2]PyrG strain was used to optimise the whey medium. Maximum endoglucanase activity of 46 U/mL was produced on 10% whey medium containing 0.6% NaNO3. The results obtained indicate that dairy whey can be utilised as a feedstock for recombinant enzyme production. However, variations in enzyme activities were observed and require further investigation.
The rise of the metaverse: tethering effect and intellectual property of crypto tokens
Authors: Wyczik Jakub
Published: February 2024

Tokens, as digital content and virtual goods, require a comprehensive, multi-layered approach for analysis. This approach, which is generally applicable to various such goods, examines the legal status of tokens on three distinct layers: first, the rights to the virtual good itself; second, the rights to the assets linked to the virtual good; third, the rights to the intellectual property (IP) intricately associated with the token. This article examines issues of the associated rights concerning the general tethering effect, formal requirements for the transfer of IP rights, licensing, the doctrine of first sale (exhaustion), the concept of the lawful acquirer and other crucial cross-border aspects of IP in the realm of virtual goods, particularly in the emerging metaverse. The present contribution provides practitioners and researchers with a guide to tethering effects and IP in the context of tokens. It also highlights the need to change current paradigms due to the growing importance and actual existence of virtual property.
Association of N-terminal pro–brain natriuretic peptide with survival among US cancer survivors
Authors: Cao Chao , Yang Lin , Nohria Anju , Mayer Erica L , Partridge Ann H , Ligibel Jennifer A
Published: February 2024

Background

N-terminal pro–brain natriuretic peptide (NT-proBNP) is a cardiac biomarker associated with the risk of heart failure and death in the general population, but it has not been explored in cancer survivors.

Methods

Using a US nationally representative sample of adults 20 years of age and older from the National Health and Nutrition Examination Survey from 1999 to 2004, this study compared NT-proBNP levels between adults without cancer (n = 12 574) and adult cancer survivors (n = 787). It examined the association of NT-proBNP with all-cause and cause-specific mortality among cancer survivors.

Results

Cancer survivors had higher NT-proBNP levels than adults without cancer (median [interquartile range] = 125.4 pg/mL [52.4-286.0] vs 43.2 pg/mL [20.3-95.0]). In particular, survivors of breast, prostate, and colorectal cancers had higher NT-proBNP levels than adults without cancer (multivariable-adjusted P < .05). In total, 471 survivors died (141 from cancer; 95 from cardiac disease) during a median follow-up period of 13.4 years (9393 person-years). Among cancer survivors, higher NT-proBNP levels were statistically associated with increased risks of all-cause death (hazard ratio [HR] = 1.31, 95% confidence interval [CI] = 1.18 to 1.46) and cardiac death (HR = 1.55, 95% CI = 1.21 to 2.00) but not with death from cancer (HR = 1.10, 95% CI = 0.92 to 1.32]). Higher NT-proBNP levels were associated with elevated overall mortality in survivors of prostate cancer (HR = 1.49, 95% CI = 1.22 to 1.81) and colorectal cancer (HR = 1.78, 95% CI = 1.00 to 3.16) (P = .169 for interaction). Nonlinear dose-response relationships were observed between NT-proBNP and mortality, with statistically significant relationships emerging above 125 pg/mL.

Conclusions

Cancer survivors had higher NT-proBNP levels than adults without cancer, and elevated NT-proBNP levels were associated with higher risks of all-cause and cardiac mortality in cancer survivors.
Parameterization of height–diameter and crown radius–diameter relationships across the globe
Authors: Song Xiang , Li Jinxu , Zeng Xiaodong
Published: February 2024

The tree height–diameter at breast height (H–DBH) and crown radius–DBH (CR–DBH) relationships are key for forest carbon/biomass estimation, parameterization in vegetation models and vegetation–atmosphere interactions. Although the H–DBH relationship has been widely investigated on site or regional scales, and a few of studies have involved CR–DBH relationships based on plot-level data, few studies have quantitatively verified the universality of these two relationships on a global scale. This study evaluated the ability of 29 functions to fit the H–DBH and CR–DBH relationships for six different plant functional types (PFTs) on a global scale, based on a global plant trait database. Results showed that most functions were able to capture the H–DBH relationship for tropical PFTs and boreal needleleaf trees relatively accurately, but slightly less for temperate PFTs and boreal broadleaf trees (BB). For boreal PFTs, the S-shaped Logistic function fitted the H–DBH relationship best, while for temperate PFTs the Chapman–Richards function performed well. For tropical needleleaf trees, the fractional function of DBH satisfactorily captured the H–DBH relationship, while for tropical broadleaf trees, the Weibull function and a composite function of fractions were the best choices. For CR–DBH, the fitting capabilities of all the functions were comparable for all PFTs except BB. The Logistic function performed best for two boreal PFTs and temperate broadleaf trees, but for temperate needleleaf trees and two tropical PFTs, some exponential functions demonstrated higher skill. This work provides valuable information for parameterization improvements in vegetation models and forest field investigations.
Kinetics of Conventional and New Cardiac Radiotracers
Authors: Klein Ran , deKemp Robert A. , Rotstein Benjamin , Yoshinaga Keiichiro
Published: February 2024

Cardiac nuclear imaging relies on the principles of tracer kinetics for the assessment of cardiovascular physiology, including perfusion, metabolism, neurohormonal signaling, and cell signaling. Tracer kinetics are used to describe the exchange between blood and tissue, and between different biochemical forms within the physical tissue spaces. Properties such as a high extraction fraction are desirable for quantification of myocardial blood flow, whereas a high retention fraction is essential for myocardial perfusion imaging with high tissue-to-blood contrast. Tracer washout rates can be used to measure metabolic substrate utilization or clearance of metabolic byproducts. The combination or balance of tracer uptake and washout rates can be used to measure the apparent volume of distribution, reflecting the combined density and affinity of a receptor or transporter. Appropriate selection of tracer and kinetic parameters provides a powerful means to study a wide range of biological processes in the living body.
Artifacts
Authors: Van Decker William A.
Published: February 2024

Artifacts are not unique to nuclear cardiac imaging and are observed in many aspects of patient care. All imaging modalities (such as echocardiography, chest x-rays, computed tomography of any type, magnetic resonance imaging, coronary angiography, and electrocardiography) may have artifacts due to the imaging technique. Their recognition and correction improves precision and patient management. With nuclear cardiology, artifacts could be observed with SPECT and PET as well as with radionuclide angiography. The greater number of SPECT studies means that more artifacts are observed with SPECT than PET. Artifacts may affect interpretation of perfusion pattern, LV function, and myocardial blood flow. Artifacts are simply defined as changes in any of the above measurements that are created by the imaging process itself rather than any real biologic or physiologic process. Some are obvious, but others are much more subtle. They could be due to image acquisition, processing, software, hardware, automation, and extracardiac activity. Understanding the causes of the common artifacts will allow recognition of the signature “footprint” on final images. Some artifacts lend themselves to image generation mitigation and others to classic pattern recognition. This chapter will characterize artifacts and explain common ways to manage each for clinically improved interpretation.
Nuclear Cardiac Imaging in Women
Authors: Taqueti Viviany R. , de Souza Ana Carolina do A. H.
Published: February 2024

Heart disease is the number-one cause of death in women worldwide, and important sex differences in the rates of diagnosis, utilization of care, response to therapy and clinical outcomes have been described. Conventional diagnostic testing approaches in the evaluation of ischemic heart disease, which were designed primarily for identification of obstructive CAD, can lead to under- or over-testing in women without differentiating those most at risk. Unique factors related to the presentation, diagnosis, and underlying pathophysiology of ischemic heart disease in women underscore the need for a more tailored risk assessment strategy. Extensive evidence supports that MPI with SPECT and PET can effectively risk stratify women with ischemic heart disease. This chapter reviews how advances in nuclear cardiology techniques, including the addition of (1) absolute quantification of coronary blood flow and reserve, (2) multiparametric imaging approaches with MPI and CT, and (3) strategies to reduce radiation dose with the use of ultra-low-dose protocols involving stress-only imaging, solid-state detector SPECT, and PET, are being applied to better capture pathologic phenotypes prevalent in women, including ischemia with no obstructive CAD and coronary microvascular dysfunction, which may be important contributors to their morbidity and mortality.
Approach to the Patient With Abnormal Liver Test Results and Acute Liver Failure
Authors: Poterucha John J.
Published: February 2024

Abnormal liver test results are defined as abnormal results for aminotransferases (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) or hepatic alkaline phosphatase (ALP). Determination of currently used “normal” values most likely included patients who had clinically unrecognized liver disease such as nonalcoholic fatty liver disease. It has been suggested that the upper limit of the normal value for ALT should be 33 U/L for men and 25 U/L for women. Population-based studies suggest that 25% of the population has an abnormal ALT value and 33% an abnormal ALP value. Abnormal liver test results are generally defined as acute if the duration is less than 3 months or chronic if the duration is more than 3 months.
Clinical Approach to Liver Mass Lesions
Authors: Roberts Lewis R.
Published: February 2024

The clinical approach to liver mass lesions requires attention to the clinical context within which the mass is identified, the symptoms of the patient, and the physical examination, laboratory tests, and imaging studies. With the advent of frequent ultrasonographic or cross-sectional imaging of the abdomen for various abdominal symptoms, many liver mass lesions are now discovered incidentally during imaging performed for unrelated symptoms. These incidentally discovered lesions should be evaluated fully because a large proportion of them indicate the presence of malignant or premalignant disease that requires appropriate management. This chapter describes the overall approach to the evaluation and diagnosis of liver mass lesions and summarizes the clinical features and management of the most common benign and malignant liver masses.
Ascites, Hepatorenal Syndrome, and Encephalopathy
Authors: Kulai Tasha B. , Simonetto Douglas A.
Published: February 2024

The portal hypertension and hepatic synthetic dysfunction of cirrhosis cause 3 main complications as liver disease progresses from compensated to decompensated disease: variceal bleeding, ascites, and hepatic encephalopathy. Ascites is the most common major complication of cirrhosis and occurs within 10 years in about 50% of patients who have compensated cirrhosis. The development of ascites denotes the transition from compensated to decompensated cirrhosis as it is often the first decompensating event.
Gallstones
Authors: Vargas Valls Eric J.
Published: February 2024

Over 20 million people in the US are affected by gallbladder-related diseases, and the estimated direct annual costs exceed $6.3 billion. The formation of gallstones, cholelithiasis, affects people throughout the world, but the prevalence varies among different groups, ranging from 60% to 70% among American Indians to 5% among persons in sub-Saharan Africa. In the US, 20% of patients with cholelithiasis have gallstone-related complications (annual incidence rate, 1%-4%), and more than 700,000 cholecystectomies are performed annually. This chapter reviews the anatomy, development, physiology, clinical manifestations, diagnosis, and management of gallstone and gallstone-related diseases.
A 63-Year-Old Woman With Recurrent Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: Kanj Amjad N. , Nelson Darlene R.
Published: February 2024

Bronchoscopic lung volume reduction benefits a subset of patients who have severe emphysema and are still symptomatic after receiving optimal medical therapy. Target lobe selection and careful assessment of collateral ventilation are important for successful bronchoscopic lung volume reduction. An important risk for patients undergoing bronchoscopic lung volume reduction is pneumothorax.
A 67-Year-Old Woman With Hyperglycemia
Authors: Subat Yosuf W. , Nguyen Kianna M. , Oeckler Richard A.
Published: February 2024

Small cell lung cancer can cause ectopic corticotropin release and development of Cushing syndrome. Life-threatening complications of rapidly progressive hypercortisolemia include severe electrolyte abnormalities and infections. Etomidate is a highly effective inhibitor of adrenal steroidogenesis and should be considered in patients who require urgent correction of cortisol levels. A low-dose infusion of etomidate is unlikely to cause sedation and may serve as a bridge to surgical intervention in patients with refractory hypercortisolemia.
A 51-Year-Old Man With Fatigue, Dyspnea, and Lung Nodules
Authors: Koslow Matthew , Baqir Misbah , Ryu Jay H.
Published: February 2024

The evaluation of pulmonary nodules requires consideration of several factors, including the patient’s underlying risk for malignancy, nodule characteristics, and systemic conditions associated with pulmonary manifestations. Society guidelines and prediction equations may support management decisions, which should ultimately be made on a case-by-case basis.
A 48-Year-Old Man With Recurrent Pneumonia
Authors: Egan Ashley M. , Limper Andrew H.
Published: February 2024

Although relatively rare, blastomycosis should be considered when patients present with pulmonary symptoms suggestive of pneumonia that have not responded to traditional treatment, especially if other organs are involved. Blastomycosis warrants treatment with antifungal therapy, usually itraconazole, although amphotericin B is appropriate in specific circumstances.
A 37-Year-Old Man With Sudden Loss of Vision
Authors: del Valle Kathryn T. , Edell Eric S.
Published: February 2024

The fungal pathogen C gattii commonly occurs in the Pacific Northwest and most often affects the lungs, central nervous system, and eyes. Unlike its better-known relative, C neoformans, C gattii occurs more often in immunocompetent rather than immunocompromised hosts and is notably more likely to cause large pulmonary and brain mass lesions known as crytococcomas. If a diagnosis of C gattii infection is strongly suspected, lumbar puncture, funduscopic examination, and head and chest imaging should be routinely performed. Standard treatment typically includes induction antifungal therapy with amphotericin B and flucytosine with subsequent prolonged treatment with fluconazole.
A 49-Year-Old Man With Dizziness, Fatigue, Muscle Weakness, and Shortness of Breath
Authors: Wegner Wippel Catherine , Schiavo Dante N. , Kern Ryan M.
Published: February 2024

Pulmonary carcinoids are a subgroup of well-differentiated lung neuroendocrine tumors. Typical carcinoids have a more indolent course and carry a better prognosis than atypical carcinoids. Most tumors arise in the proximal airways, and patients present with cough, wheeze, hemoptysis, chest pain, and recurrent pneumonia. The preferred treatment is surgery. Radiotherapy with or without chemotherapy can be considered for patients who are not surgical candidates.
A 46-Year-Old Woman With Progressive Shortness of Breath
Authors: Teague Taylor T. , Midthun David E.
Published: February 2024

Chylothorax is a rare cause of pleural effusion. Fluid may not appear chylous, so a high degree of awareness is required, especially when patients have compatible risk factors. Pleural fluid from chylothorax usually has a milky appearance, exudative characteristics, and a predominance of lymphocytes. The diagnosis can be made confidently if the pleural fluid triglyceride level exceeds 110 mg/dL in the appropriate clinical context. Treatment is multimodal and incorporates conservative measures such as the use of dietary modification, TPN, and somatostatin analogues. If conservative therapy is unsuccessful, more aggressive measures, such as pleurodesis or thoracic duct ligation or embolization, can be pursued.
A 59-Year-Old Man With Progressive Shortness of Breath and Fatigue 18 Months After Bilateral Lung Transplant
Authors: Tarmey Tara , Roden Anja C. , Kennedy Cassie C.
Published: February 2024

The differential diagnosis is broad when patients have late-onset dyspnea after lung transplant. After acute and reversible causes have been excluded, chronic lung allograft dysfunction (CLAD) is an important consideration if the patient has a marked, sustained decrease in forced expiratory volume in the first second of expiration. Early recognition and appropriate subtyping of CLAD aid in providing a prognosis and tailoring the therapy.
GW190425: Pan-STARRS and ATLAS coverage of the skymap and limits on optical emission associated with FRB 20190425A
Authors: Smartt S J , Nicholl M , Srivastav S , Huber M E , Chambers K C , Smith K W , Young D R , Fulton M D , Tonry J L , Stubbs C W , Denneau L , Cooper A J , Aamer A , Anderson J P , Andersson A , Bulger J , Chen T -W , Clark P , de Boer T , Gao H , Gillanders J H , Lawrence A , Lin C C , Lowe T B , Magnier E A , Minguez P , Moore T , Rest A , Shingles L , Siverd R , Smith I A , Stalder B , Stevance H F , Wainscoat R , Williams R
Published: February 2024

GW190425 is the second of two binary neutron star (BNS) merger events to be significantly detected by the Laser Interferometer Gravitational Wave (GW) Observatory (LIGO), Virgo and the Kamioka Gravitational Wave (KAGRA) detector network. With a detection only in LIGO Livingston, the skymap containing the source was large and no plausible electromagnetic counterpart was found in real-time searching in 2019. Here, we summarize Asteroid Terrestrial-Impact Last Alert System (ATLAS) and Panoramic Survey Telescope and Rapid Response System (Pan-STARRS) wide-field optical coverage of the skymap beginning within 1 and 3 h, respectively, of the GW190425 merger time. More recently, a potential coincidence between GW190425 and a fast radio burst FRB 20190425A has been suggested, given their spatial and temporal coincidences. The smaller sky localization area of FRB 20190425A and its dispersion measure led to the identification of a likely host galaxy, UGC 10667 at a distance of 141 ± 10 Mpc. Our optical imaging covered the galaxy 6.0 h after GW190425 was detected and 3.5 h after the FRB 20190425A. No optical emission was detected and further imaging at +1.2 and +13.2 d also revealed no emission. If the FRB 20190425A and GW190425 association were real, we highlight our limits on kilonova emission from a BNS merger in UGC 10667. The model for producing FRB 20190425A from a BNS merger involves a supramassive magnetized neutron star spinning down by dipole emission on the time-scale of hours. We show that magnetar-enhanced kilonova emission is ruled out by optical upper limits. The lack of detected optical emission from a kilonova in UGC 10667 disfavours, but does not disprove, the FRB–GW link for this source.
Protoclusters as drivers of stellar mass growth in the early Universe, a case study: Taralay – a massive protocluster at z ∼ 4.57
Authors: Staab Priti , Lemaux Brian C , Forrest Ben , Shah Ekta , Cucciati Olga , Lubin Lori , Gal Roy R , Hung Denise , Shen Lu , Giddings Finn , Khusanova Yana , Zamorani Giovanni , Bardelli Sandro , Cassara Letizia Pasqua , Cassata Paolo , Chiang Yi-Kuan , Fudamoto Yoshinobu , Fukushima Shuma , Garilli Bianca , Giavalisco Mauro , Gruppioni Carlotta , Guaita Lucia , Gururajan Gayathri , Hathi Nimish , Kashino Daichi , Scoville Nick , Talia Margherita , Vergani Daniela , Zucca Elena
Published: February 2024

Simulations predict that the galaxy populations inhabiting protoclusters may contribute considerably to the total amount of stellar mass growth of galaxies in the early universe. In this study, we test these predictions observationally, using the Taralay protocluster (formerly PCl J1001+0220) at z ∼ 4.57 in the COSMOS field. With the Charting Cluster Construction with VUDS and ORELSE (C3VO) survey, we spectroscopically confirmed 44 galaxies within the adopted redshift range of the protocluster (4.48 < z < 4.64) and incorporate an additional 18 galaxies from ancillary spectroscopic surveys. Using a density mapping technique, we estimate the total mass of Taralay to be ∼1.7 × 1015 M⊙, sufficient to form a massive cluster by the present day. By comparing the star formation rate density (SFRD) within the protocluster (SFRDpc) to that of the coeval field (SFRDfield), we find that SFRDpc surpasses the SFRDfield by Δlog (SFRD/M⊙yr−1 Mpc−3) = 1.08 ± 0.32 (or ∼12 ×). The observed contribution fraction of protoclusters to the cosmic SFRD adopting Taralay as a proxy for typical protoclusters is $33.5~{{\ \rm per\ cent}}^{+8.0~{{\ \rm per\ cent}}}_{-4.3~{{\ \rm per\ cent}}}$, a value ∼2σ higher than the predictions from simulations. Taralay contains three peaks that are 5σ above the average density at these redshifts. Their SFRD is ∼0.5 dex higher than the value derived for the overall protocluster. We show that 68 per cent of all star formation in the protocluster takes place within these peaks, and that the innermost regions of the peaks encase $\sim 50~{{\ \rm per\ cent}}$ of the total star formation in the protocluster. This study strongly suggests that protoclusters drive stellar mass growth in the early universe and that this growth may proceed in an inside-out manner.
Dust-to-neutral gas ratio of the intermediate- and high-velocity H i clouds derived based on the sub-mm dust emission for the whole sky
Authors: Hayakawa Takahiro , Fukui Yasuo
Published: February 2024

We derived the dust-to-H i ratio of the intermediate-velocity clouds (IVCs), the high-velocity clouds (HVCs), and the local H i gas, by carrying out a multiple-regression analysis of the 21 cm H i emission combined with the sub-mm dust optical depth. The method covers over 80 per cent of the sky contiguously at a resolution of 47 arcmin and is distinguished from the absorption-line measurements toward bright galaxies and stars covering a tiny fraction of the sky. Major results include that the ratio of the IVCs is in a range of 0.1–1.5 with a mode at 0.6 (relative to the solar-neighbourhood value, likewise below) and that a significant fraction, ∼20 per cent, of the IVCs include dust-poor gas with a ratio of <0.5. It is confirmed that 50 per cent of the HVC Complex C has a ratio of <0.3, and that the Magellanic Stream has the lowest ratio with a mode at ∼0.1. The results prove that some IVCs have low metallicity gas, contrary to the previous absorption-line measurements. Considering that the recent works show that the IVCs are interacting and exchanging momentum with the high-metallicity Galactic halo gas, we argue that the high-metallicity gas contaminates a significant fraction of the IVCs. Accordingly, we argue that the IVCs include a significant fraction of the low-metallicity gas supplied from outside the Galaxy as an alternative to the Galactic-fountain model.