bluuebunny/crossref_metadata_2025 huggingface dataset:
Perspectives on production factors, health benefits, safety, and prospects of African fermented cereals and vegetables: a review
Authors: Fang Kewei , Liu Chunhong , Olatunji Opeyemi Joshua , Suttihkana Itthanan , Ashaolu Tolulope Joshua
Published: January 2025

Africa is home to some of the world’s fermented foods including cereal- and vegetable-based fermented products. The fermentation of cereals (e.g., maize, millet, teff, wheat, sorghum, etc.) and vegetables (e.g., pumpkin leaves, cowpea leaves, amaranth, roselle, melon, etc.) of African origin is affected by several factors, which consequently affect their nutritional status and health benefits. Ethnic and modern knowledge indicate that these fermented products offer numerous health benefits ranging from antioxidant to gut health enhancement. This review provides perspectives on African fermented cereals and vegetables. The factors affecting their production including variety, quality, microbial composition, water quality, pH, temperature, processing techniques, cultural practices, post-fermentation conditions, and good hygiene practices were discussed. Subsequently, the fermented products’ health benefits (e.g., improved nutrient bioavailability, enhanced digestibility, and probiotic effect) and safety concerns (risk of contamination, mycotoxin, biogenic amines formation, etc.) are provided before unravelling the prospects of African fermented foods.
Influence of the Maillard reaction on the structure of β-casein using a simulated cooking system
Authors: Xu Dan , Yang Tangyu , Tan Zhihao , Wu Guixian , Xu Jiancong , Li Lin , Li Bing , Yang Yipeng
Published: January 2025

Glycation during food processing can change the structural characteristics of dietary protein and endow a variety of functionalities. Milk β-casein (MC) with five different types of carbohydrates (i.e., glucose, sucrose, amylose, amylopectin, and soluble starch) in a simulated cooking system at 98 and 115 °C was investigated. The changes in ultraviolet absorption, endogenous fluorescence intensity, surface hydrophobicity, particle size, free amino group, free sulphydryl group, and circular dichroism were measured. For the glucose-added group, the lowest free amino content and most significant spectral changes among all groups were observed after heating at 115 °C for 6 hr (OH-MC-Glu). Results showed that glycation activities of five sugars were glucose > sucrose > soluble starch> amylopectin ≈ amylose. Under the simulated cooking system, the secondary structure and conformation of glycated MC changed to different degrees, which were affected by the glycation degree. Moderate glycation (0–2 hr of heating) may promote the conversion reaction of sulfhydryl-disulfide bond (SH-SS) in MC, causing cross-linking and self-aggregation of MC, and induce the particle size increase of MC. Excessive glycation (2–6 hr of heating) can further reduce the surface hydrophobicity of MC, inhibit self-aggregation of MC, and reduce the particle size of MC.
Safety and Immunogenicity of SARS-CoV-2 Spike Receptor-Binding Domain and N-Terminal Domain mRNA Vaccine
Authors: Chalkias Spyros , Pragalos Antionette , Akinsola Adebayo , Berman Gary , Ampajwala Madhavi , Meyer Jay , Schoch Lorraine , Zhou Wen , Paila Yamuna D , Deng Weiping , Feng Jing , de Windt Elizabeth , Edwards Darin , Miller Jacqueline , Das Rituparna
Published: January 2025

Background

mRNA-1283 is an investigational coronavirus disease 2019 (COVID-19) mRNA vaccine encoding the receptor-binding and N-terminal domains of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein in contrast to the original mRNA-1273 vaccine, which encodes the full-length spike protein.

Methods

A phase 2a, dose-ranging, observer-blind, randomized study conducted in adults (aged ≥18 years) previously vaccinated with mRNA-1273 evaluated the safety and immunogenicity of a single dose of mRNA-1283 (2.5, 5, and 10 µg) and its bivalent formulation, mRNA-1283.211 (5 and 10 µg; encoding original SARS-CoV-2 and Beta) against the comparator mRNA-1273 vaccine, 50 µg (part A). A subsequent, open-label study (part B) evaluated the safety and immunogenicity of a monovalent Omicron BA.1 vaccine, mRNA-1283.529 (5 and 10 µg).

Results

A total of 340 participants were randomized in part A, and 200 participants were enrolled in part B. All dose levels of mRNA-1283 vaccines were well tolerated and increased the neutralizing antibody (nAb) responses at day 29 compared to baseline against SARS-CoV-2 D614G and Beta. The nAb responses elicited by mRNA-1283 were higher than those elicited by mRNA-1273. mRNA-1283.529 (part B) increased nAb at day 29 against Omicron BA.1. Antibody responses remained detectable for a year postvaccination.

Conclusions

mRNA-1283 was well tolerated and exhibited improved immunogenicity compared to mRNA-1273.

Clinical Trials Registration

NCT05137236.
Prevalence of drug resistance mutations in low-level viremia patients under antiretroviral therapy in Southwestern China: a cross-sectional study
Authors: Shu Yuanlu , Liu Jiafa , Yang Cuixian , Li Jianjian , Zhang Mi , Li Yuan , Deng Xuemei , Dong Xingqi
Published: January 2025

Objectives

This study aimed to evaluate the prevalence and characteristics of drug resistance mutations (DRMs) in patients with low-level viremia (LLV) in Southwestern China, as it has become a growing challenge in AIDS clinical practice.

Methods

This cross-sectional study was performed in Yunnan Province, Southwestern China. LLV was defined as 50–999 copies/mL of plasma viral load with antiretroviral therapy (ART) for at least 6 months. HIV-1 DRM detection used validated in-house protocol.

Results

A total of 470 sequences were obtained, and 13 HIV-1 genotypes were identified, among which CRF08_BC (47.5%), CRF07_BC (22.3%) and CRF01_AE (10.0%) subtypes were the most prevalent. The overall prevalence of DRMs was 45.7% (215/470), and the prevalence of DRMs to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) was 39.4% (185/470), 20.6% (97/470) and 5.3% (25/470), respectively. The most common NNRTI-associated mutations were K103N (16.0%), E138A (6.6%), V179D (6.6%) and P225H (4.9%), and those in NRTIs were M184V (17.0%), D67N (3.4%) and K65R (3.0%). PI-associated mutations were infrequent, occurring in less than 1.8% of cases. The prevalence of NNRTI-associated mutations (K101E and Y188C) was found to be statistically significant among various LLV groups. Additionally, significant variations were observed in the prevalence of NNRTI-associated mutations (V106I, V106M, E138A and P225H), NRTI-associated mutation (K65R) and PI-associated mutations (L33F and Q58E) across different subtypes.

Conclusions

The prevalence of DRMs in ART-experienced patients with LLV was high, and HIV-1 genotypes exhibited diversity in Yunnan Province. These findings indicate that regular DRM monitoring during LLV episodes was essential for effective clinical treatment and management in this region.
Smart Imitator: Learning from Imperfect Clinical Decisions
Authors: Perera Dilruk , Liu Siqi , See Kay Choong , Feng Mengling
Published: January 2025

Objectives

This study introduces Smart Imitator (SI), a 2-phase reinforcement learning (RL) solution enhancing personalized treatment policies in healthcare, addressing challenges from imperfect clinician data and complex environments.

Materials and Methods

Smart Imitator’s first phase uses adversarial cooperative imitation learning with a novel sample selection schema to categorize clinician policies from optimal to nonoptimal. The second phase creates a parameterized reward function to guide the learning of superior treatment policies through RL. Smart Imitator’s effectiveness was validated on 2 datasets: a sepsis dataset with 19 711 patient trajectories and a diabetes dataset with 7234 trajectories.

Results

Extensive quantitative and qualitative experiments showed that SI significantly outperformed state-of-the-art baselines in both datasets. For sepsis, SI reduced estimated mortality rates by 19.6% compared to the best baseline. For diabetes, SI reduced HbA1c-High rates by 12.2%. The learned policies aligned closely with successful clinical decisions and deviated strategically when necessary. These deviations aligned with recent clinical findings, suggesting improved outcomes.

Discussion

Smart Imitator advances RL applications by addressing challenges such as imperfect data and environmental complexities, demonstrating effectiveness within the tested conditions of sepsis and diabetes. Further validation across diverse conditions and exploration of additional RL algorithms are needed to enhance precision and generalizability.

Conclusion

This study shows potential in advancing personalized healthcare learning from clinician behaviors to improve treatment outcomes. Its methodology offers a robust approach for adaptive, personalized strategies in various complex and uncertain environments.
Comparing the effects of verbenone, methyl salicylate, and permethrin on attacks of ambrosia beetles (Coleoptera: Curculionidae Scolytinae) in ornamental nurseries
Authors: Govindaraju Ramkumar , Joseph Shimat V
Published: January 2025

The granulate ambrosia beetle, Xylosandrus crassiusculus (Motschulsky), and the black stem borer, Xylosandrus germanus (Blandford) are important pests in ornamental nurseries in the eastern USA. These beetles are managed mainly using preventative trunk applications of pyrethroids, such as permethrin or bifenthrin when females typically fly out of woodlots and attack young trees in the spring. Verbenone and methyl salicylate are potential phytochemicals reported as repellants but not completely validated in ornamental nurseries for ambrosia beetle management as an alternative option. Thus, this study aimed to compare the efficacy of verbenone alone or with methyl salicylate and permethrin on ambrosia beetle attacks. In 2023 and 2024, a study was conducted where verbenone (with methyl salicylate) and permethrin were combined with 10% and 50% ethanol-infused maple bolts. Verbenone alone or combined with methyl salicylate did not reduce ambrosia beetle attacks on bolts compared to permethrin. Permethrin was effective in reducing ambrosia beetle attacks on bolts. This suggests that permethrin is still the best option to prevent ambrosia beetle attacks on young trees in ornamental nurseries.
Antitrust Protectionism: Escaping the Perils of Anti-Suit Injunctions Through WTO Law
Authors: Borgogno Oscar
Published: January 2025

This piece delves into the global surge of antitrust litigation involving intellectual property–related “antisuit injunctions” (“ASIs”), a judicial remedy with extraterritorial impact aimed at curtailing patent holders from enforcing their rights protecting technologies essential for the implementation of technical standards (standard essential patents). Litigants are racing to secure their preferred legal venue for establishing worldwide licensing rates, while also attempting to prevent patent holders from initiating patent infringement proceedings elsewhere using ASIs. This phenomenon poses an inherent risk of exacerbating the current trade fragmentation trend across geopolitical blocks and has already led to an ongoing dispute at the World Trade Organization between the European Union and China. This paper argues that the Agreement on Trade-Related Aspects of Intellectual Property Rights offers a readily available solution to counter the perils of antitrust protectionism by prohibiting barriers to legitimate trade that do not include safeguards against abuse of enforcement procedures (that is, ASIs with an overly broad scope).
Sickle cell disease severity and outcomes in Anuak patients: a scoping review
Authors: Geway Gemechu , Prokop Larry J , Ferdjallah Asmaa
Published: January 2025

Southeast Minnesota is home to a significant population of Anuak individuals who seek care within the Mayo Clinic Health Systems. The city of Austin, MN is home to a population numbering around 450 Anuak individuals who are seen at the Mayo Clinic Austin location as well as the Rochester main campus of Mayo Clinic. In total, more than 3000 Anuak individuals live in Minnesota in what is considered to be the largest Anuak population outside of East Africa. For pediatric patients with SCD, 15 of 20 (75%) are Anuak. The majority of these patients have severe SCD with chronic anemia, frequent pain crises, cardiac ventricular enlargement, acute chest pain, and multiple hospital admissions. The objective of this review is to understand what is known about SCD, the severity of phenotype, and outcomes in the published literature regarding this special population. A scoping review was conducted using primarily OVID databases. Only 2 studies met established criteria. Unfortunately, both sources of literature were dated and not consistent with current trends. Despite communicating with colleagues in Ethiopia, there does not exist accurate or robust data about the incidence or prevalence of SCD among the Anuak people. The local Anuak diaspora in Southeast Minnesota likely represents the best current data and representation in this patient population. There is a need for further research regarding SCD outcomes in this special population.
Mesonephric-like adenocarcinoma of the ovary: a case study
Authors: Assila Saad , Khmou Mouna , Mahdi Youssef , El Khannoussi Basma
Published: January 2025

Mesonephric-like adenocarcinoma (MLA) is a rare and newly recognized subtype of ovarian and endometrial carcinomas, introduced in the 2020 World Health Organization Classification. This tumor likely originates from Müllerian-derived tissues and often mimics more common ovarian cancers, leading to frequent misdiagnosis. This case study details a 36-year-old woman who presented with urinary symptoms following a hysterectomy. Imaging revealed a significant left ovarian mass, initially misdiagnosed as carcinosarcoma. Pathological evaluation ultimately confirmed MLA, characterized by diverse architectural patterns and specific immunohistochemical markers. The patient underwent chemotherapy due to the locally advanced disease. This case highlights the diagnostic challenges of MLA and emphasizes the need for awareness among clinicians to prevent misdiagnosis. Given its aggressive nature and tendency to early recurrence, further research is essential for establishing standardized diagnostic criteria and treatment protocols for this rare malignancy.
The role of thermal feedback in the growth of planetary cores by pebble accretion in dust traps
Authors: Cummins Daniel P , Owen James E
Published: January 2025

High-resolution millimetre-imaging of protoplanetary discs has revealed many containing rings and gaps. These rings can contain large quantities of dust, often in excess of 10 $\mathrm{ M}_{\oplus }$, providing prime sites for efficient and rapid planet formation. Rapid planet formation will produce high accretion luminosities, heating the surrounding disc. We investigate the importance of a planetary embryo’s accretion luminosity by simulating the dynamics of the gas and dust in a dust ring, accounting for the energy liberated as a resident planetary embryo accretes. The resulting heating alters the flow structure near the planet, increasing the accretion rate of large, millimetre-to-centimetre-sized dust grains. We show how this process varies with the mass of dust in the ring and the local background gas temperature, demonstrating that the thermal feedback always acts to increase the planet’s mass. This increase in planet mass is driven primarily by the formation of vortices, created by a baroclinic instability once the accreting planet heats the disc significantly outside its Hill radius. The vortices can then migrate with respect to the planet, resulting in a complex interplay between planetary growth, gap-opening, dust trapping, and vortex dynamics. Planets formed within dust traps can have masses that exceed the classical pebble isolation mass, potentially providing massive seeds for the future formation of giant planets. Once pebble accretion ceases, the local dust size distribution is depleted in large grains, and much of the remaining dust mass is trapped in the system’s L$_5$ Lagrange point, providing potentially observable signatures of this evolution.
Differences in the autoantibody phenotypes and long-term outcomes between juvenile- and adult-onset systemic sclerosis
Authors: Tsuji Hideaki , Shirakashi Mirei , Hiwa Ryosuke , Akizuki Shuji , Nakashima Ran , Onishi Akira , Yoshifuji Hajime , Tanaka Masao , Morinobu Akio
Published: January 2025

Objective

To investigate differences in autoantibodies, clinical features, and long-term outcomes between juvenile- and adult-onset systemic sclerosis (SSc).

Methods

Autoantibodies and survival rates over a maximum of 20 years were retrospectively analysed in 504 Japanese patients with SSc (juvenile-onset SSc, n = 17; adult-onset SSc, n = 487) using data from Kyoto University Registry.

Results

: The autoantibodies observed were anti-topoisomerase-I (71% vs. 26%), anti-centromere (24% vs. 54%), and anti-RNA-polymerase-III (0% vs. 12%). A diffuse type and multiorgan involvement were observed in patients with anti-topoisomerase-I in both juvenile- and adult-onset SSc. In patients with anti-centromere, a diffuse type (juvenile-onset SSc vs. adult-onset SSc, 75% vs. 28%) and pulmonary fibrosis (50% vs. 17%) were more frequently observed in juvenile-onset SSc than in adult-onset SSc. Cox proportional hazard analyses showed that older onset (hazard ratio: 1.06, 95% confidence interval: 1.03–1.09) was associated with death, while autoantibodies were not significantly associated with death. Cumulative survival rates for 20 years were similar between juvenile- and adult-onset SSc when classified based on the presence of anti-centromere (100% vs. 89%, P = .20) and anti-topoisomerase-I (90% vs. 90%, P = .70).

Conclusions

: Juvenile-onset SSc had more frequent diffuse-type and anti-topoisomerase-I. An older onset was slightly associated with mortality, whereas autoantibodies were not associated with mortality.
Coronavirus Disease 2019 (COVID-19) Real World Data Infrastructure: A Big-Data Resource for Study of the Impact of COVID-19 in Patient Populations With Immunocompromising Conditions
Authors: Crawford James M , Penberthy Lynne , Pinto Ligia A , Althoff Keri N , Assimon Magdalene M , Cohen Oren , Gillim Laura , Hammonds Tracy L , Kapur Shilpa , Kaufman Harvey W , Kwasny David , Liew Jean W , Meyer William A , Reynolds Shannon L , Schleicher Cheryl B , Subbiah Suki , Theruviparampil Catherine , Wallace Zachary S , Warner Jeremy L , Yoon Suhyeon , Ziemba Yonah C
Published: January 2025

Background

We developed a United States–based real-world data resource to better understand the continued impact of the coronavirus disease 2019 (COVID-19) pandemic on immunocompromised patients, who are typically underrepresented in prospective studies and clinical trials.

Methods

The COVID-19 Real World Data infrastructure (CRWDi) was created by linking and harmonizing de-identified HealthVerity medical and pharmacy claims data from 1 December 2018 to 31 December 2023, with severe acute respiratory syndrome coronavirus 2 virologic and serologic laboratory data from major commercial laboratories and Northwell Health; COVID-19 vaccination data; and, for patients with cancer, 2010 to 2021 National Cancer Institute Surveillance, Epidemiology, and End Results registry data.

Results

The CRWDi contains 4 cohorts: patients with cancer; patients with rheumatic diseases receiving pharmacotherapy; noncancer solid organ and hematopoietic stem cell transplant recipients; and people from the general population including adults and pediatric patients. The project successfully linked and harmonized longitudinal, de-identified data on 5.2 million unique patients using privacy-preserving record lineage techniques. The system was developed in early 2024 and rapidly deployed, enabling longitudinal analysis of patient healthcare over the full geography of delivery settings and exploration of novel questions for populations at high risk for adverse outcomes.

Conclusions

The successful development of the CRWDi enables researchers to address unanswered questions that have arisen during the COVID-19 pandemic. By making the data broadly and freely available to academic researchers, this real-world data system represents an important complement to existing consortia and clinical trials that have emerged during the healthcare crisis and is readily reproducible for future purposing.
Using mobile phone survey paradata for process evaluations and improvements: best practices and lessons learned from nine surveys in seven sites
Authors: Siesel Casey J , Lee Juliette , Phadnis Rachael , Davlin Stacy , Brevik Tobias , Lea Veronica
Published: January 2025

The use of mobile phone surveys (MPS) for regionally or nationally representative data allows for quick, efficient and affordable data collection for monitoring trends and generating results to guide action. By digitizing this process, data flows can be expanded to include metadata and paradata that allow survey administrators to evaluate and improve survey processes and parameters. Between 2017 and early 2022, the Centers for Disease Control and Prevention provided technical support to country partners to implement MPS gathering indicators on noncommunicable diseases within adult populations in seven countries. These surveys resulted in 37 591 completed interviews containing no personal identifiable information. When combined, these surveys result in over 25 million rows of paradata representing timestamped interactions between the data collection platform and each survey respondent. Using exploratory data analysis, five key metrics were identified which had implications on MPS process optimization: timing of engagement, question randomization, contacts to complete, errors and mode effect. The use of survey paradata allows for real-time process evaluations and identifies factors that can improve efficiency and effectiveness of MPS methods.
What Explains German Länder Governments’ Stances Towards Federalism?
Authors: Barbaro Salvatore , Rode Julia M
Published: January 2025

In federal systems, subnational governments often take highly asymmetric positions on questions of self-rule and shared rule. The German case is emblematic of this dynamic, as some state governments assert their primary role in legislative functions while others highlight the benefits of coordinated and uniform decision-making. Although the existing literature recognizes these differences, it often fails to fully disentangle the underlying reasons for this variation. This article examines several factors shaping the divergent positions of Länder, including historical legacies, party ideology, and cultural and religious differences. Our findings indicate that financial capacity is a key determinant of Länder governments’ stances on federalism questions.
What is rheumatoid factor? From screening to personalized management
Authors: Tanaka Yoshiya
Published: January 2025

The RF is a representative autoantibody against the crystallizable fragment (Fc) of denatured IgG that is primarily detected in patients with RA. Although five types of TNF inhibitors can be used to treat RA, no guidelines are available for selecting the appropriate inhibitor for treatment. High serum RF levels are associated with high disease activity, progressive joint destruction, life prognosis associated with organ damage, decreased treatment responsiveness to TNF inhibitors and other drugs and low treatment retention rates. Meanwhile, certolizumab pegol (CZP), a TNF inhibitor without the Fc region, remains at high concentrations in the blood. Unlike other antibody drugs with the Fc region, CZP maintains efficacy in patients with high serum RF levels. When serum IgM-RF levels are high, antibody drugs with the Fc region are more likely to bind to IgM-RF and be degraded. Thus, CZP without the Fc region may be more favourable for patients with high serum RF levels.
The internationalization of science parks in China from a realist international relations perspective
Authors: Malta-Kira Thomas , Fu Xiaolan , Shi Liu
Published: January 2025

Science parks have been an integral component of the open national innovation system (ONIS). However, science park internationalization as an important yet neglected mechanism of international innovation cooperation is poorly understood. There has been limited understanding of the political dynamics in the international system that affect the nature and process of ‘opening’. This paper fills the gap by exploring the factors affecting internationalization of science parks from a realist perspective of international relations against the background of ONIS, based on case studies on China’s science parks. The results support our propositions that political interference in both China as the rising power and the dominant power (USA) has been a major factor affecting performance of science park internationalization when the process of ‘opening’ is intertwined with the strategic interests of the state on both sides. Findings from the study suggest the reconfiguration of ONIS in geopolitical context with significant policy implications.
Prevalence and impact of exploding head syndrome in a Japanese working population
Authors: Tsovoosed Uyanga , Sumi Yukiyoshi , Ozeki Yuji , Harada Akiko , Kadotani Hiroshi
Published: January 2025

Study Objectives

Exploding head syndrome (EHS) is a parasomnia characterized by the perception of loud noises, or explosions inside the head during the sleep-to-wake transition. The prevalence of EHS remains unclear. This survey aimed to elucidate the prevalence of and factors associated with EHS in this cohort.

Methods

As part of the Night in Japan Home Sleep Monitoring Study (NinjaSleep study), a cross-sectional survey was conducted among government employees in Koka City, Shiga Prefecture, Japan, in 2022. Participants were queried regarding their experiences with EHS as defined in the International Classification of Sleep Disorders, 3rd Edition, including sudden loud noises or sensations of explosions, subsequent abrupt awakenings and feelings of fright. Various standardized instruments were employed to evaluate depression, anxiety, insomnia, quality of life, and fatigue.

Results

Of the 2081 employees invited to participate, 1878 completed the survey. After excluding respondents with epilepsy and incomplete responses, 1843 participants were deemed eligible for analysis. Among them, 46 (2.49%) reported experiencing sudden noises or sensations of explosions, with 23 (1.25%) meeting the diagnostic criteria for EHS. The EHS was significantly related to the scores on the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Athens insomnia scale, and Chalder fatigue scale, even after adjusting for age, sex, body mass index, and categorized mean sleep duration.

Conclusion

This study elucidates the prevalence of EHS among the Japanese population and underscores its potential association with insomnia symptoms and various psychological factors.
Cross-resistance between Pseudomonas chlororaphis strain AFS009 metabolites (Howler EVO) and fludioxonil in Botrytis cinerea
Authors: Wesche Johanna , Repp Jacqueline , Hu Mengjun , Faust James , Schnabel Guido
Published: January 2025

Howler EVO is a biological fungicide based on metabolites of the bacterium Pseudomonas chlororaphis strain AFS009. One of the metabolites, pyrrolnitrin (PRN), is a chemical analogue of the phenylpyrrole fludioxonil used to manage gray mold of fruit crops caused by Botrytis cinerea. Resistance to fludioxonil in B. cinerea is well documented and linked to mutations in the transcription factor mrr1, leading to overexpression of the ATP-Binding Cassette (ABC) transporter gene BcatrB. Moderately resistant isolates are designated MDR1 and MRD1h based on the specific variation of mutations in mrr1 and the level of BcatrB expression. This study investigated EC50 values of 54 B. cinerea isolates sensitive and with moderate resistance to fludioxonil for sensitivity to fludioxonil and Howler EVO. The Pearson correlation coefficient indicated a strong correlation between EC50 values of fludioxonil and Howler EVO. Isolates that were moderately resistant to fludioxonil and classified as MDR strains were also moderately resistant to Howler EVO. The effect of Howler EVO and fludioxonil on BcatrB gene expression was studied by qPCR. Both fungicides induced the BcatrB gene expression significantly up to 100-fold in sensitive B. cinerea isolates. Howler EVO significantly induced the BcatrB gene expression in all MDR1 isolate but not in the MDR1h isolate. In detached fruit assays on cherry, sensitive B. cinerea isolates were completely inhibited by formulated fludioxonil (Scholar) and significantly suppressed in growth by Howler EVO. However, MDR1 and MDR1h isolates produced disease in Scholar and Howler EVO treatments. Our results indicate cross-resistance between the synthetic fungicide fludioxonil and the biofungicide Howler EVO, indicating that, at least for some biofungicides, resistance management is necessary.
Pseudocercospora fengxinensis, a new species causing sooty spot of kiwifruit in China
Authors: Hu Yuzhuan , Yuan Xinen , Cheng Shuyuan , Liu Bing , Zhang Jinyi , Peng Zhen , Gao Xinyu , Jiang Junxi , Xiong Guihong
Published: January 2025

Pseudocercospora is a large cosmopolitan genus of plant pathogenic fungi that are commonly associated with leaf and fruit spots as well as blights on a wide range of plant hosts. P. actinidiae is a member of this genus, causing sooty spot on kiwifruit worldwide. With the expansion of kiwifruit cultivation, the incidence of sooty spot has become severe in Fengxin County, Jiangxi Province, China. Based on a survey conducted in 2022 across nine kiwifruit cultivars in six local orchards, the results showed that the disease incidence was higher in ‘Donghong’, ‘Jinyan’, ‘Jinkui’, ‘Fenghuang No. 1’ and ‘Jinguo’. In contrast, it was lower in ‘Gold3’ and ‘Hongshi No. 2’. No lesions were observed on ‘Kuilv’ and ‘Miliang No. 1’. 31 fungal strains were isolated from infected leaves using single-spore isolation. Phylogenetic analysis of combined sequence data from the internal transcribed spacer region of ribosomal DNA (ITS), partial actin (actA), translation elongation factor 1-alpha (tef1), and the second largest subunit of RNA polymerase II (rpb2) sequence data, using maximum-likelihood (ML) and Bayesian inference (BI), revealed their taxonomic placement within Pseudocercospora. Both morphological and molecular phylogenetic analysis supported Pseudocercospora fengxinensis as a new taxon within Pseudocercospora. Pathogenicity tests confirmed P. fengxinensis as the causal agent of sooty spot on kiwifruit. This study is the first report of P. fengxinensis causing sooty spot of kiwifruit worldwide, enriching our understanding of Pseudocercospora diversity in China and providing a foundation for improved disease management strategies.
FABP5 regulates ROS‐NLRP3 inflammasome in glutamate‐induced retinal excitotoxic glaucomatous model
Authors: Zeng Zhou , You Mengling , Fan Cong , Jiang Jian , Xia Xiaobo
Published: January 2025

Fatty acid binding proteins (FABPs) are a class of small molecular mass intracellular lipid chaperone proteins that bind to hydrophobic ligands, such as long‐chain fatty acids. FABP5 expression was significantly upregulated in the N‐methyl‐d‐aspartic acid (NMDA) model, the microbead‐induced chronic glaucoma model, and the DBA/2J mice. Previous studies have demonstrated that FABP5 can mediate mitochondrial dysfunction and oxidative stress in ischemic neurons, but the role of FABP5 in oxidative stress and cell death in retina NMDA injury models is unclear. In this study, we found that FABP5 is significantly altered in a model of glutamate excitotoxicity and is regulated by Stat3. Inhibition of FABP5 alleviated oxidative stress imbalance and activation of NLRP3 inflammasome, reduced the release of inflammatory factors, and ultimately attenuated glutamate excitotoxicity‐induced retinal ganglion cell loss. Meanwhile, caspase1 inhibitors could alleviate the retinal ganglion cell loss induced by glutamate excitotoxicity. In conclusion, FABP5 inhibition protects retina ganglion cells from excitotoxic damage by suppressing the ROS‐NLRP3 inflammasome pathway. FABP5 maybe a promising new target for glaucoma diagnosis and treatment.
Hantaan virus glycoprotein Gc induces NEDD4‐dependent PTEN ubiquitination and degradation to escape the restriction of autophagosomes and facilitate viral propagation
Authors: Lu Shuang , Chen Shuliang , Zhang Yuqing , Mou Xiaoli , Li Mingyang , Zhu Shaowei , Chen Xingyuan , Strandin Tomas M. , Jiang Yale , Xiang Zhoufu , Liu Yuanyuan , Xiong Hairong , Guo Deyin , Chen Liangjun , Li Yirong , Hou Wei , Luo Fan
Published: January 2025

Hantaan virus (HTNV) infection causes severe hemorrhagic fever with renal syndrome (HFRS) in humans and the infectious process can be regulated by autophagy. The phosphatase and tensin homolog (PTEN) protein has antiviral effects and plays a critical role in the autophagy pathway. However, the relationship between PTEN and HTNV infection is not clear and whether PTEN‐regulated autophagy involves in HTNV replication is unknown. Here, we identified that HTNV infection inhibits PTEN expression in vitro and in vivo. The HTNV glycoprotein Gc promotes PTEN ubiquitination and degradation through 26S‐proteasome pathway via the E3 ubiquitin ligase NEDD4. In addition, knockdown of PTEN prevents autophagy and increases HTNV production, while overexpression of PTEN induces autophagosome formation which can wrap HTNV particles, thus leading to restrain the production of progeny viruses. Altogether, our findings reveal the role of PTEN in HTNV infection by autophagy, highlighting the potential importance of PTEN and autophagy in the treatment of HFRS diseases.
What is the Surgical Burden of Treatment for High-Energy Lower Extremity Trauma? A Secondary Analysis of the OUTLET Study
Authors: Stewart Christopher C. , Reider Lisa , Soifer Rachel , Namiri Nikan K. , O'Toole Robert V. , Karunakar Madhav A , Potter Benjamin K. , Bosse Michael , Morshed Saam ,   METRC
Published: January 2025

OBJECTIVES:

To describe and enumerate surgeries for patients who underwent reconstruction or amputation after severe distal tibia, ankle, and mid to hindfoot injuries.

METHODS:

Design: Secondary analysis of a multicenter prospective observational study

Setting:

31 U.S. level-I trauma centers and 3 military treatment facilities

Patient Selection Criteria:

Participants aged 18 to 60 with Gustilo type-III pilon (OTA 43B or 43C), IIIB or C ankle fracture (OTA 44A, 44B, or 44C), type-III talar or calcaneal fracture (OTA 81B, 82B, or 82C), or open or closed crush or blast injuries to the hindfoot or midfoot who underwent limb reconstruction or amputation from 2012 to 2017.

Outcome Measurements and Comparisons:

Number of temporizing, definitive, and complication surgeries were compared by treatment and injury.

RESULTS:

574 participants with 221 ankle and pilon, 140 talus and calcaneal, and 213 other foot injuries were followed for 18 months. The mean age was 38 (range 8-64) and 33% were female. Participants underwent reconstruction (n=472), primary amputation (n=76), and failed reconstruction followed by amputation (n=26). 841 temporizing, 958 definitive, and 501 complication surgeries were performed. The number of surgeries was highest for those who underwent failed reconstruction (mean 5.8, 95% CI: 4.9-6.8, range 3-13) compared to reconstruction (mean 3.8, 95% CI: 3.5-4.0, range 1-21), and primary amputation (mean 4.9, 95% CI: 4.3-5.5, range 2-14) (p<0.01). Those with ankle and pilon injuries required more surgeries (4.7, 95% CI: 4.3-5.1, range 1-21) than hindfoot (3.4, 95% CI: 3.0-3.7, range 1-10), and other foot injuries (3.7, 95% CI: 3.4-4.0, range 1-14) (p<0.01). The average participant would complete definitive treatment 23 days after their injury, and those who required surgery for a complication spent 41 days in the complication phase of treatment.

CONCLUSIONS:

Patients with high-energy lower extremity trauma underwent nearly 4 surgeries over 3 weeks until completion of definitive treatment, regardless of whether they underwent limb reconstruction or amputation. Those with ankle or pilon injuries and failed reconstruction attempts experienced the most operations, and those with complications required over an additional month of surgical care. These data may inform a shared decision-making process around limb optimization.

LEVEL OF EVIDENCE:

Therapeutic Level II
“Atlanta Is Like Wakanda … but With Real Big, Big Issues”
Authors: Tran Thi Phuong Thao , Menyongai Jeremiah , Foster Jordan , Scheib Isabel , Allen Ashley Kay , Graham Lisa , Li Fei , Spears Claire A. , Stauber Christine E. , Dolan Kathleen A. , Owen-Smith Ashli A. , Lynch Nicole A. , Weaver Scott R. , Huang Jidong , Arias Jalayne J. , Cormier Jacque-Corey , Popova Lucy
Published: January 2025

Background and Objectives: This qualitative study explored perceived community strengths and health issues among 3 underserved and under-studied populations in the Atlanta, Georgia—older adults, Black or African American persons, and refugees/immigrants/migrants. Methods: Eight focus groups were conducted with 92 participants who were members of the 3 populations in Atlanta between November 2022 and March 2023. Results: Although there were variations among groups, all groups emphasized diversity within their community as the foundation of community strength. Elements of the built environment such as parks, convenience stores, the Atlanta Beltline, and food outlets bolstered community strength. Furthermore, community members being able to voice concerns and the responsiveness of governmental institutions helped form strong relationships to build a strong community. Regarding health issues, common physical health concerns included hypertension and obesity, with varied mental health issues. Accessibility and affordability of healthy foods were significant social concerns, alongside challenges in healthcare access such as navigating complex systems and high medical costs. Conclusion: Tailored interventions recognizing community strengths and addressing specific health issues are crucial for improving outcomes in marginalized communities, necessitating a health-in-all policies approach considering social, cultural, and structural determinants of health.
Resolution of hypertension after kidney transplantation is associated with improved kidney transplant outcomes: a nationwide cohort study
Authors: Lee Kyungho , Kim Bong-Sung , Jeon Junseok , Shin Dong Wook , Lee Jung Eun , Huh Wooseong , Han Kyung-Do , Jang Hye Ryoun
Published: January 2025

Objectives:

Patients with advanced chronic kidney disease suffer from hypertension, and kidney transplantation (KT) has potential to induce hypertension resolution. We hypothesized that hypertension resolution after KT is associated with better KT outcomes.

Methods:

We identified KT recipients (2006–2015) who had pretransplant hypertension. They were categorized into two groups based on their hypertension status after KT: persistent vs. resolved hypertension, using data from the Korea National Health Insurance System. Cox proportional hazard analyses were performed to assess the risk of graft failure and mortality, adjusting for various clinical factors.

Results:

Among 11 317 KT recipients with pretransplant hypertension, 7269 (64%) remained hypertensive, while 4048 (36%) experienced hypertension resolution. Recipients with resolved hypertension exhibited a lower prevalence of delayed graft function and major comorbidities, including diabetes, ischemic heart disease, and stroke. Graft failure and mortality rates were significantly lower in resolved hypertension group. After adjusting for multiple covariates, hazard ratios of resolved hypertension were 0.61 (95% confidence interval 0.52–0.72) for graft failure and 0.68 (0.56–0.81) for all-cause mortality.

Conclusions:

A significant proportion of patients experienced hypertension resolution after KT, which is associated with improved graft and overall survival. The post-KT hypertension resolution can be used as a prognostic indicator for predicting better KT outcomes.
Impacts of hypertension and diabetes on the incidence of cardiovascular diseases and all-cause mortality: findings from the China Health and Retirement Longitudinal Study cohort
Authors: Tu Qiang , Hyun Karice , Lin Shuanglan , Hafiz Nashid , Manandi Deborah , Li Emily , Wang Xinzheng , Wu Haisheng , Redfern Julie
Published: January 2025

Objective:

The study aimed to examine the individual and joint effects of hypertension and diabetes on cardiovascular diseases and all-cause mortality among the middle-aged and older Chinese population.

Methods:

A total of 9681 individuals without preexisting CVD from the China Health and Retirement Longitudinal Study (CHARLS) were included. Participants were classified into four different groups: hypertension alone, diabetes alone, both conditions, neither condition. Multivariate Cox proportional hazards models were performed to estimate the risks of all-cause mortality and CVD.

Results:

During the 7-year follow-up, 967 deaths and 1535 CVD events were documented. Compared to individuals without hypertension and diabetes, hypertension alone [adjusted hazard ratio (aHR) 1.571, 95% confidence interval (CI) 1.316–1.875, P < 0.001], diabetes alone (aHR 1.618, 95% CI 1.187–2.205, P < 0.01) and comorbid hypertension and diabetes (aHR 2.041, 95% CI 1.557–2.677, P < 0.001) increased risks of all-cause mortality. The aHRs for CVD events in individuals with both conditions, hypertension alone and diabetes only were 2.011 (95% CI 1.651–2.449, P < 0.001), 1.408 (95% CI 1.233–1.608, P < 0.001) and 1.036 (95% CI 0.808–1.327, P > 0.05), respectively. The risk of CVD among those with comorbid hypertension and diabetes exceeded the sum of the risks due to hypertension and diabetes alone (relative excess risk ratio = 0.567, 95% CI 0.136–0.999).

Conclusion:

Individuals with comorbid hypertension and diabetes had greater risks of CVD and all-cause mortality, beyond those associated with either condition alone. The synergistic interaction between hypertension and diabetes aggravated the risk of CVD.
Formulas to estimate dietary sodium intake from spot urine lead to misleading associations with cardiovascular disease risk and mortality
Authors: Song Jing , Wang Changqiong , Pombo-Rodrigues Sonia , MacGregor Graham A. , Campbell Norm R.C. , He Feng J.
Published: January 2025

Objectives:

To test the hypothesis that the association of formula-estimated sodium intake from spot urine with cardiovascular disease is independent of spot urinary sodium concentration.

Methods:

We included 435 336 participants in the UK Biobank whose sodium intake was estimated from spot urine using INTERSALT, Kawasaki, and Tanaka formulas. Hazard ratios for cardiovascular disease (CVD) events and deaths were estimated using Cox proportional-hazard model adjusted for multiple covariates. Penalized Cox regression was used to assess nonlinear relations. Hazard ratios were recalculated after replacement of the sodium concentration term with sex-specific mean values (women: 67.5 mmol/l; men: 89.8 mmol/l) to assess how other components of the formulas influenced these associations.

Results:

Forty-four thousand two hundred and sixty-eight CVD events and 3251 CVD deaths occurred during a median follow-up of 12 years. The mean estimated sodium intake was 143 (SD = 35), 178 (52), and 147 (33) mmol/day based on INTERSALT, Kawasaki, and Tanaka formulas, respectively. For CVD incidence, linear inverse associations were observed for INTERSALT and Tanaka estimates [hazard ratios (95% CIs) for every 50 mmol increase in estimated sodium intake: 0.9 (0.83–0.97) and 0.93 (0.89– 0.97); P-linear = 0.0047 and 0.0021], and a U-shaped association for the Kawasaki estimates (P-nonlinear = 0.0026). When the sodium concentration term was fixed, inverse associations were seen for all formulas [0.86 (0.77–0.95), 0.96 (0.93–0.99) and 0.94 (0.89–0.99) for INTERSALT, Kawasaki, and Tanaka; P linear = 0.0054, 0.0166 and 0.0188]. For CVD mortality, no association was observed, but a nonlinear association was identified for the INTERSALT equation (P-nonlinear = 0.0287) after fixing the sodium concentration.

Conclusion:

These formula-estimated sodium intakes were associated with CVD incidence and mortality independently of spot urinary sodium concentration. We recommend these formulas not be used in studies associating sodium intake with CVD outcomes to avoid generating misleading evidence.
Diabetes Endothelial Keratoplasty Study: Methods and Impact on the Use of Corneas From Donors With Diabetes for Descemet Membrane Endothelial Keratoplasty
Authors: Price Marianne O. , Szczotka-Flynn Loretta B. , Bauza Colleen E. , Reed Zachariah W. , Benetz Beth Ann , Greiner Mark A. , Verdier David D. , Soper Mark C. , Titus Michael S. , Monnier Vincent M. , Arafah Baha M. , Kollman Craig , Beck Roy W. , Lass Jonathan H. ,   Writing Committee for the Diabetes Endothelial Keratoplasty Study Group
Published: January 2025

Purpose:

Describe aims, methods, characteristics of donors, donor corneas and recipients, and potential impact of the Diabetes Endothelial Keratoplasty Study (DEKS).

Methods:

The DEKS is a randomized, clinical trial to assess graft success and endothelial cell density (ECD) 1 year after Descemet membrane endothelial keratoplasty (DMEK) using corneas from donors with versus without diabetes in a 1:2 minimization assignment. Diabetes severity in the donor is assessed by medical history, postmortem HbA1c, and donor skin advanced glycation end-products and oxidation markers. A central image analysis reading center assesses baseline donor, 1-month and 1-year postoperative ECD.

Results:

The DEKS used corneas from 1154 donors for 1421 DMEK procedures on 1097 participants (324 bilateral) at 28 clinical sites. Forty-eight tissue preparations failed (3%). Mean donor age was 65 years; mean eye bank–determined screening ECD was 2709 cells/mm2. Ultimately, 106 (9%) of 1154 donors without diabetes history were classified as diabetic based on postmortem HbA1c ≥6.5%, and 509 (36%) of 1421 donor lenticules were classified as coming from diabetic donors. Recipients were 58% female, 96% White, and 53% phakic. Study eyes were treated for Fuchs endothelial corneal dystrophy (96%), pseudophakic corneal edema (2%), and failed endothelial keratoplasty (2%). Mean recipient age was 70 years; 21% had diabetes history and 26 (2%) had central laboratory determined HbA1c ≥6.5% without diabetes history.

Conclusions:

The DEKS will increase understanding of factors related to DMEK success while determining whether diabetes and/or diabetes severity in the donor and/or recipient adversely affects graft success and endothelial cell loss.
Lucia Keratoprosthesis in a Sclerocorneal Graft for Recurrent Graft Rejection Secondary to Herpetic Keratitis
Authors: Ortiz-Morales Gustavo , Serrano-Robles José Gerardo , Vera-Duarte Guillermo Raul , Rodríguez-Loaiza José Luis , Navas Alejandro , Ramirez-Miranda Arturo , Graue-Hernandez Enrique O.
Published: January 2025

Purpose:

To report the surgical approach of a Lucia keratoprosthesis (KPro) on a sclerocorneal graft in the setting of recurrent graft rejection and perilimbal scleral thinning.

Methods:

A case report.

Results:

We report the case of a 26-year-old man with a history of herpes simplex keratitis, 2 penetrating keratoplasties, graft failure, secondary glaucoma, and a conjunctival flap in the right eye who underwent a Lucia KPro, lens extraction, glaucoma drainage device, and pars plana vitrectomy. The surgery involved releasing the conjunctival flap, revealing severe perilimbal scleral thinning. The use of a sclerocorneal graft to mount the Lucia KPro allowed an effective combined procedure by providing a healthy sclera. At the last follow-up (34 months), the patient had retained the Lucia KPro and had a best-corrected visual acuity of 20/400.

Conclusions:

The Lucia KPro on a sclerocorneal graft may be a viable option to provide healthy sclera in patients requiring combined KPro surgery.