bluuebunny/crossref_metadata_2025 huggingface dataset:
Deconstructing dams and disease: predictions for salmon disease risk following Klamath River dam removals
Authors: Bartholomew Jerri L. , Alexander Julie D. , Alvarez Justin , Atkinson Stephen D. , Belchik Michael , Bjork Sarah J. , Foott J. Scott , Gonyaw Alex , Hereford Mark E. , Holt Richard A. , McCovey Barry , Som Nicholas A. , Soto Toz , Voss Anne , Williams Thomas H. , Wise Ted G. , Hallett Sascha L.
Published: October 2023

The health of fish populations and the river systems they inhabit have broad ecological, cultural, recreational, and economic relevance. This is exemplified by the iconic anadromous salmonid fishes native to the West Coast of North America. Salmon populations have been constrained since the mid nineteenth century by dam construction and water reallocation. In the Klamath River (Oregon and California, USA), a series of dams built in the early-mid 20th century cut the basin in two and blocked anadromous fish access to more than 600 river kilometers. This dramatic loss of habitat, coupled with infectious diseases and resulting epizootics, have impacted the wellbeing of these salmonid populations. In 2023-2024, the Klamath River will undergo the largest river restoration project in US history. Removal of the four lowermost dams will cause profound physical changes to the river, including flow, water temperature, and channel geomorphology. The dam removals will reconnect the lower and upper portions of the basin, and provide fish passage after a century of segregation. Reestablishment of upstream and downstream fish movements will also alter the occupancy and abundance of the salmonid hosts and their pathogens. The increased habitat availability and longer migration routes will increase duration of pathogen exposure and potential impacts on juvenile survival and adult pre-spawn mortality. However, restoration of more natural flow and sediment regimes will decrease overall fish disease risk by disrupting complex parasite life cycles. To better understand these multifarious, competing factors, we review the salmonid species in the Klamath River, and provide an overview of their historical pathogen challenges and associated diseases and use this as a framework to predict the effects of dam removals on disease dynamics. Our review and predictions are a synthesis of expertise from tribal biologists, fish health specialists and fish biologists, many of whom have lived and worked on the Klamath River for decades. We conclude with recommendations for expansion of current pathogen monitoring and research efforts to measure changes in host-pathogen dynamics basin-wide.
Mediport use as an acceptable standard for CAR T cell infusion
Authors: Eylon Maya , Prabhu Snehit , John Samuel , King Maxwell J. M. , Bhatt Dhruv , Curran Kevin J. , Erickson Courtney , Karras Nicole A. , Phillips Christine L. , Satwani Prakash , Hermiston Michelle , Southworth Erica , Baumeister Susanne H. C. , Talano Julie-An , MacMillan Margaret L. , Rossoff Jenna , Bonifant Challice L. , Myers Gary Doug , Rouce Rayne H. , Toner Keri , Driscoll Timothy A. , Katsanis Emmanuel , Salzberg Dana B. , Schiff Deborah , De Oliveira Satiro N. , Capitini Christian M. , Pacenta Holly L. , Pfeiffer Thomas , Shah Niketa C. , Huynh Van , Skiles Jodi L. , Fraint Ellen , McNerney Kevin O. , Quigg Troy C. , Krueger Joerg , Ligon John A. , Fabrizio Vanessa A. , Baggott Christina , Laetsch Theodore W. , Schultz Liora M.
Published: October 2023

Introduction

Mediport use as a clinical option for the administration of chimeric antigen receptor T cell (CAR T cell) therapy in patients with B-cell malignancies has yet to be standardized. Concern for mediport dislodgement, cell infiltration, and ineffective therapy delivery to systemic circulation has resulted in variable practice with intravenous administration of CAR T cell therapy. With CAR T cell commercialization, it is important to establish practice standards for CAR T cell delivery. We conducted a study to establish usage patterns of mediports in the clinical setting and provide a standard of care recommendation for mediport use as an acceptable form of access for CAR T cell infusions.

Methods

In this retrospective cohort study, data on mediport use and infiltration rate was collected from a survey across 34 medical centers in the Pediatric Real-World CAR Consortium, capturing 504 CAR T cell infusion routes across 489 patients. Data represents the largest, and to our knowledge sole, report on clinical CAR T cell infusion practice patterns since FDA approval and CAR T cell commercialization in 2017.

Results

Across 34 sites, all reported tunneled central venous catheters, including Broviac® and Hickman® catheters, as accepted standard venous options for CAR T cell infusion. Use of mediports as a standard clinical practice was reported in 29 of 34 sites (85%). Of 489 evaluable patients with reported route of CAR T cell infusion, 184 patients were infused using mediports, with no reported incidences of CAR T cell infiltration.

Discussion/Conclusion

Based on current clinical practice, mediports are a commonly utilized form of access for CAR T cell therapy administration. These findings support the safe practice of mediport usage as an accepted standard line option for CAR T cell infusion.
Simian immunodeficiency virus-infected rhesus macaques with AIDS co-develop cardiovascular pathology and encephalitis
Authors: White Kevin S. , Walker Joshua A. , Wang John , Autissier Patrick , Miller Andrew D. , Abuelezan Nadia N. , Burrack Rachel , Li Qingsheng , Kim Woong-Ki , Williams Kenneth C.
Published: October 2023

Despite effective antiretroviral therapy, HIV co-morbidities remain where central nervous system (CNS) neurocognitive disorders and cardiovascular disease (CVD)-pathology that are linked with myeloid activation are most prevalent. Comorbidities such as neurocogntive dysfunction and cardiovascular disease (CVD) remain prevalent among people living with HIV. We sought to investigate if cardiac pathology (inflammation, fibrosis, cardiomyocyte damage) and CNS pathology (encephalitis) develop together during simian immunodeficiency virus (SIV) infection and if their co-development is linked with monocyte/macrophage activation. We used a cohort of SIV-infected rhesus macaques with rapid AIDS and demonstrated that SIV encephalitis (SIVE) and CVD pathology occur together more frequently than SIVE or CVD pathology alone. Their co-development correlated more strongly with activated myeloid cells, increased numbers of CD14+CD16+ monocytes, plasma CD163 and interleukin-18 (IL-18) than did SIVE or CVD pathology alone, or no pathology. Animals with both SIVE and CVD pathology had greater numbers of cardiac macrophages and increased collagen and monocyte/macrophage accumulation, which were better correlates of CVD-pathology than SIV-RNA. Animals with SIVE alone had higher levels of activated macrophage biomarkers and cardiac macrophage accumulation than SIVnoE animals. These observations were confirmed in HIV infected individuals with HIV encephalitis (HIVE) that had greater numbers of cardiac macrophages and fibrosis than HIV-infected controls without HIVE. These results underscore the notion that CNS and CVD pathologies frequently occur together in HIV and SIV infection, and demonstrate an unmet need for adjunctive therapies targeting macrophages.
Exosomes multifunctional roles in HIV-1: insight into the immune regulation, vaccine development and current progress in delivery system
Authors: Habib Arslan , Liang Yulai , Zhu Naishuo
Published: October 2023

Human Immunodeficiency Virus (HIV-1) is known to establish a persistent latent infection. The use of combination antiretroviral therapy (cART) can effectively reduce the viral load, but the treatment can be costly and may lead to the development of drug resistance and life-shortening side effects. It is important to develop an ideal and safer in vivo target therapy that will effectively block viral replication and expression in the body. Exosomes have recently emerged as a promising drug delivery vehicle due to their low immunogenicity, nanoscale size (30-150nm), high biocompatibility, and stability in the targeted area. Exosomes, which are genetically produced by different types of cells such as dendritic cells, neurons, T and B cells, epithelial cells, tumor cells, and mast cells, are designed for efficient delivery to targeted cells. In this article, we review and highlight recent developments in the strategy and application of exosome-based HIV-1 vaccines. We also discuss the use of exosome-based antigen delivery systems in vaccine development. HIV-1 antigen can be loaded into exosomes, and this modified cargo can be delivered to target cells or tissues through different loading approaches. This review also discusses the immunological prospects of exosomes and their role as biomarkers in disease progression. However, there are significant administrative and technological obstacles that need to be overcome to fully harness the potential of exosome drug delivery systems.
Recombinant C1 inhibitor in the prevention of severe COVID-19: a randomized, open-label, multi-center phase IIa trial
Authors: Urwyler Pascal , Leimbacher Marina , Charitos Panteleimon , Moser Stephan , Heijnen Ingmar A. F. M. , Trendelenburg Marten , Thoma Reto , Sumer Johannes , Camacho-Ortiz Adrián , Bacci Marcelo R. , Huber Lars C. , Stüssi-Helbling Melina , Albrich Werner C. , Sendi Parham , Osthoff Michael
Published: October 2023

Background

Conestat alfa (ConA), a recombinant human C1 inhibitor, may prevent thromboinflammation.

Methods

We conducted a randomized, open-label, multi-national clinical trial in which hospitalized adults at risk for progression to severe COVID-19 were assigned in a 2:1 ratio to receive either 3 days of ConA plus standard of care (SOC) or SOC alone. Primary and secondary endpoints were day 7 disease severity on the WHO Ordinal Scale, time to clinical improvement within 14 days, and safety, respectively.

Results

The trial was prematurely terminated because of futility after randomization of 84 patients, 56 in the ConA and 28 in the control arm. At baseline, higher WHO Ordinal Scale scores were more frequently observed in the ConA than in the control arm. On day 7, no relevant differences in the primary outcome were noted between the two arms (p = 0.11). The median time to defervescence was 3 days, and the median time to clinical improvement was 7 days in both arms (p = 0.22 and 0.56, respectively). Activation of plasma cascades and endothelial cells over time was similar in both groups. The incidence of adverse events (AEs) was higher in the intervention arm (any AE, 30% with ConA vs. 19% with SOC alone; serious AE, 27% vs. 15%; death, 11% vs. 0%). None of these were judged as being related to the study drug.

Conclusion

The study results do not support the use of ConA to prevent COVID-19 progression.

Clinical trial registration

https://clinicaltrials.gov, identifier NCT04414631.
A census of quality-controlled Biogeochemical-Argo float measurements
Authors: Stoer Adam C. , Takeshita Yuichiro , Maurer Tanya Lea , Begouen Demeaux Charlotte , Bittig Henry C. , Boss Emmanuel , Claustre Hervé , Dall’Olmo Giorgio , Gordon Christopher , Greenan Blair John William , Johnson Kenneth S. , Organelli Emanuele , Sauzède Raphaëlle , Schmechtig Catherine Marie , Fennel Katja
Published: October 2023

Biogeochemical- (BGC-) Argo aims to deploy and maintain a global array of autonomous profiling floats to monitor ocean biogeochemistry. With over 250,000 profiles collected so far, the BGC-Argo network is rapidly expanding toward the target of a sustained fleet of 1,000 floats. These floats prioritize the measurement of six key properties: oxygen, nitrate, pH, chlorophyll-a, suspended particles, and downwelling light. To assess the current biogeochemical state of the ocean, its variability, and trends with confidence, it is crucial to quality control these measurements. Accordingly, BGC-Argo maintains a quality control system using manual inspection and parameter-specific algorithms for flagging and adjusting data. In this study, we provide a census of the quantity and quality of measurements from BGC-Argo based on their quality flagging system. The purpose of this census is to assess the current status of the array in terms of data quality, how data quality has changed over time, and to provide a better understanding of the quality-controlled data to current and future users. Alongside increasing profile numbers and spatial coverage, we report that for most parameters between 80 and 95% of the profiles collected so far contain high-quality BGC data, with an exception for pH. The quality of pH profiles has seen a large improvement in the last five years and is on track to match the data quality of other BGC parameters. We highlight how BGC-Argo is improving and discuss strategies to increase the quality and quantity of BGC profiles available to users. This census shows that tracking percentages of high-quality data through time is useful for monitoring float sensor technology and helpful for ensuring the long-term success of BGC-Argo.
Ecological risk assessment of heavy metals in the coastal sediment in the South-western Bay of Bengal
Authors: Naik Subrat , Pradhan Umakanta , Karthikeyan P. , Bandyopadhyay Debasmita , Sahoo Rabindra Kumar , Panda Uma Sankar , Mishra Pravakar , Murthy M. V. Ramana
Published: October 2023

Dynamic coastal waters are often polluted by chemical pollutants, affecting coastal ecosystems. A total of four scientific coastal cruises up to 10 km offshore from the coastline along the Chennai-Puducherry coast during 2019-20 were conducted. This study examined the spatiotemporal distribution of heavy metals (Cr, Cu, Pb, Cd, Ni, Zn, As, Co, Mn) in the coastal sediments using various geochemical indices, including the Geo-accumulation Index (Igeo), Enrichment Factor (EF), Contamination Factor (CF), and Ecological Risk Index (ERI), to understand the impacts, environmental risks, and pollution status in coastal and marine systems. The heavy metal concentrations of Cr, Cu, Pb, Cd, Ni, Zn, As, Co, and Mn in sediments are 16.48-74.70 μg/g, 2.01-3.78 μg/g, 1.37-17.54 μg/g, 0.20-21.76 μg/g, and 5.73-40.53 μg/g, 4.73-53.54 μg/g, 2.09-28.18 μg/g, 1.80-9.02 μg/g, 70.27-346.22 μg/g, respectively. The Igeo results revealed that none of the metals reached up to the contamination level except for Cd and As which showed a slightly contaminated level of the sediment. ERI indicated that coastal sediments are at moderate to high ecological risk from heavy metals. This study will help policymakers make informed decisions for combating or remediating metal pollution to safeguard the coastal environment.
The philosophy of pharmaceutical regulation—Paternalism or freedom of choice?
Authors: Mahlich Jörg , Riou Sybille , Verry Matthieu
Published: October 2023

When assessing the value of new drugs regulatory authorities across the world frequently make different decisions even though their decisions are based on the same evidence package. In this perspective we argue that even in today’s world regulatory and medical decision making is framed by conflicting philosophical schools of thought, namely the liberal tradition of the Anglo Saxon countries pioneered by the Scotsman Adam Smith and the continental European tradition of paternalism that roots back to the German philosopher Georg Friedrich Hegel. We outline the basics of these two philosophical theories and show that countries following the liberal tradition are more reluctant to reject new drugs due to weak evidence. Instead, they leave decisions to a greater extend to those who are affected, namely patients and their caregivers.
Lonicera caerulea L. polyphenols improve short-chain fatty acid levels by reshaping the microbial structure of fermented feces in vitro
Authors: Cao Xinbo , Wang Xuemeng , Ren Yanxin , Sun Yangcun , Yang Zhichao , Ge Jingping , Ping Wenxiang
Published: October 2023

Increasing evidence suggests that the pathogenesis of type 2 diabetes mellitus (T2DM) is closely related to the gut microbiota. Polyphenols have been shown to alleviate T2DM, but the effects of L. caerulea L. polyphenols (LPs) on the gut microbiota and metabolites remain elusive. In this study, the inhibitory effects of fermented L. caerulea L. polyphenols (FLPs) and unfermented L. caerulea L. polyphenols (ULPs) on α-amylase and α-glucosidase and the impact of LP on the gut microbiota and metabolites were investigated. Furthermore, the relationship between the two was revealed through correlation analysis. The results showed that ULP and FLP had the highest inhibitory rates against α-amylase and α-glucosidase at 4 mg ml−1, indicating a strong inhibitory ability. In addition, LP plays a regulatory role in the concentration of short-chain fatty acids (SCFAs) and tends to restore them to their normal levels. LP reversed the dysbiosis of the gut microbiota caused by T2DM, as evidenced by an increase in the abundance of bacterial genera such as Lactobacillus, Blautia, and Bacteroides and a decrease in the abundance of bacterial genera such as Escherichia-Shigella and Streptococcus. Similarly, after LP intervention, the relationships among microbial species became more complex and interconnected. In addition, the correlation between the gut microbiota and metabolites was established through correlation analysis. These further findings clarify the mechanism of action of LP against T2DM and provide a new target for T2DM interventions.
Pleiotropic effects of Mentha longifolia L. extract on the regulation of genes involved in inflammation and apoptosis induced by Clostridioides difficile ribotype 001
Authors: Raeisi Hamideh , Azimirad Masoumeh , Abdemohamadi Elham , Pezzani Raffaele , Zali Mohammad Reza , Yadegar Abbas
Published: October 2023

Introduction

The dramatic increase in multidrug-resistance of Clostridioides difficile isolates has led to the search for new complementary medicines against C. difficile infection (CDI). In this study, we aimed to examine the inhibitory effects of hydroethanolic extract of Mentha longifolia L. (ETOH-ML) on the growth of C. difficile RT001 and its toxigenic cell-free supernatant (Tox-S)-induced inflammation and apoptosis.

Methods

The active phytochemical components of ETOH-ML were detected using GC and HPLC. The antimicrobial properties of the extract were examined against C. difficile RT001. Furthermore, cell viability and cytotoxicity of Caco-2 and Vero cells treated with various concentrations of ETOH-ML, Tox-S of C. difficile RT001, and their combination were assessed. Anti-inflammatory and anti-apoptotic activities of ETOH-ML were explored in Tox-S stimulated Caco-2 cells using RT-qPCR.

Results

Based on our results, rosmarinic acid was the main phytochemical component of ETOH-ML. The extract showed significant antimicrobial activity against C. difficile RT001 by agar dilution and broth microdilution methods. Moreover, ETOH-ML at concentrations of <25 μg/ml had no significant effect on cell viability compared to untreated cells. Treatment cells with the extract (10 or 25 μg/ml) significantly increased the cell viability and reduced the percentage of cell rounding in Caco-2 and Vero cells treated by Tox-S, respectively (P < 0.0001). Co-treatment of Tox-S stimulated Caco-2 cells with ETOH-ML showed significant anti-inflammatory and anti-apoptotic activities by downregulating the gene expression level of IL-8, IL-1β, TNF-α, iNOS, TGF-β, NF-κB, Bax, and caspase-3, while upregulating the expression level of Bcl-2.

Discussion

Our results demonstrated for the first time the antimicrobial, anti-inflammatory, and anti-apoptotic effects of M. longifolia extract on C. difficile RT001 and its Tox-S. However, further research is needed to evaluate the potential application of M. longifolia extract on CDI treatment in clinical setting.
Preliminary evaluation of the proteomic profiling in the hippocampus of aged grazing cattle
Authors: Cozzolino Flora , Canè Luisa , Sacchettino Luigi , Gatto Maria Claudia , Iacobucci Ilaria , Gatta Claudia , De Biase Davide , Di Napoli Evaristo , Paciello Orlando , Avallone Luigi , Monti Maria , d’Angelo Danila , Napolitano Francesco
Published: October 2023

Brain aging is a physiological process associated with physical and cognitive decline; however, in both humans and animals, it can be regarded as a risk factor for neurodegenerative disorders, such as Alzheimer’s disease. Among several brain regions, hippocampus appears to be more susceptible to detrimental effects of aging. Hippocampus belongs to limbic system and is mainly involved in declarative memories and context-dependent spatial-learning, whose integrity is compromised in an age-dependent manner. In the present work, taking advantage of liquid chromatography–tandem mass spectrometry (LC–MS/MS)-based proteomics, we sought to identify proteins differentially expressed in the hippocampus of the aged grazing milk cows. Our exploratory findings showed that, out of 707 identified proteins, 112 were significantly altered in old cattle, when compared to the adult controls, and functional clusterization highlighted their involvement in myelination, synaptic vesicle, metabolism, and calcium-related biological pathways. Overall, our preliminary data pave the way for the future studies, aimed at better characterizing the role of such a subcortical brain region in the age-dependent cognitive decline, as well as identifying early aging markers to improve animal welfare and husbandry practices of dairy cattle from intensive livestock.
Optimizing acute stroke treatment process: insights from sub-tasks durations in a prospective observational time and motion study
Authors: Koca Gizem , Kumar Mukesh , Gubitz Gord , Kamal Noreen
Published: October 2023

Background

Rapid treatment is critical in managing acute ischemic stroke (AIS) to improve patient outcomes. Various strategies have been used to optimize this treatment process, including the Acute Stroke Protocol (ASP) activation, and minimizing the duration of key performance metrices, such as door-to-needle time (DNT), CT-to-needle time (CTNT), CT-to-groin puncture time (CTGP), and door-to-groin puncture time (DGPT). However, identifying the delay-causing sub-tasks within the ASP could yield novel insights, facilitating optimization strategies for the AIS treatment process.

Methods

This two-phase prospective observational time and motion study aimed to identify sub-tasks and compare their respective durations involved in the treatment process for AIS patients within ASPs. The study compared sub-task durations between “routine working hours” and “evenings and weekends” (after-hours), as well as between stroke neurologists and non-stroke neurologists. Additionally, the established performance metrices of AIS were compared among the aforementioned groups.

Results

Phase 1 identified and categorized 34 sub-tasks into five broad categories, while Phase 2 analyzed the ASP for 389 patients. Among the 185 patients included in the study, 57 received revascularization treatment, with 30 receiving intravenous (IV) thrombolysis only, 20 receiving endovascular thrombectomy (EVT) only, and 7 receiving both IV thrombolysis and EVT. Significant delays were observed in sub-tasks including triage, registration, patient history sharing, treatment decisions, preparation of patients, preparation of thrombolytic agents, and angiosuite preparation. The majority of these significant delays (P < 0.05) were observed when were performed by a non-stroke neurologist and during after-hours operations. Furthermore, certain sub-tasks were exclusively performed during after-hours or when the treatment was provided by a non-stroke neurologist. Consequently, DNT, CTNT, and CTGP were significantly prolonged for both non-stroke neurologists and off-hours treatment. DGPT was significantly longer only when the ASP was conducted by non-stroke neurologists.

Conclusions

The study identified several sub-tasks that lead to significant delays during the execution of the ASP. These findings provide a premise to design targeted quality improvement interventions to optimize the ASP for these specific delay-causing sub-tasks, particularly for non-stroke neurologists and after-hours. This approach has the potential to significantly enhance the efficiency of the AIS treatment process.
Cognitive and balance functions of astronauts after spaceflight are comparable to those of individuals with bilateral vestibulopathy
Authors: Clément Gilles , Kuldavletova Olga , Macaulay Timothy R. , Wood Scott J. , Navarro Morales Deborah C. , Toupet Michel , Hautefort Charlotte , Van Nechel Christian , Quarck Gaëlle , Denise Pierre
Published: October 2023

Introduction

This study compares the balance control and cognitive responses of subjects with bilateral vestibulopathy (BVP) to those of astronauts immediately after they return from long-duration spaceflight on board the International Space Station.

Methods

Twenty-eight astronauts and thirty subjects with BVP performed five tests using the same procedures: sit-to-stand, walk-and-turn, tandem walk, duration judgment, and reaction time.

Results

Compared to the astronauts' preflight responses, the BVP subjects' responses were impaired in all five tests. However, the BVP subjects' performance during the walk-and-turn and the tandem walk tests were comparable to the astronauts' performance on the day they returned from space. Moreover, the BVP subjects' time perception and reaction time were comparable to those of the astronauts during spaceflight. The BVP subjects performed the sit-to-stand test at a level that fell between the astronauts' performance on the day of landing and 1 day later.

Discussion

These results indicate that the alterations in dynamic balance control, time perception, and reaction time that astronauts experience after spaceflight are likely driven by central vestibular adaptations. Vestibular and somatosensory training in orbit and vestibular rehabilitation after spaceflight could be effective countermeasures for mitigating these post-flight performance decrements.
Serotonin syndrome in the acute treatment landscape of migraine: the lasmiditan experience
Authors: Blumenfeld Andrew , Tepper Stewart J. , Khanna Rashna , Doty Erin , Vincent Maurice , Miller Sheila I.
Published: October 2023

Background

Serotonin syndrome (SS) symptoms overlap with adverse events associated with lasmiditan, a 5-HT (serotonin)1F receptor agonist for acute treatment of migraine. Because SS symptoms are heterogeneous, diagnosis can be challenging, and potential cases observed with lasmiditan treatment led to questions about SS pathophysiology. Here, we provide an overview of the potential risk of SS based on experience with lasmiditan.

Methods

Results of eight phase 2 and phase 3 lasmiditan trials (n = 5,916) and a controlled intravenous trial of lasmiditan (n = 88) were analyzed for symptomatology consistent with SS. Post-marketing surveillance data from lasmiditan’s US launch date (January 2020) until data cut-off (April 2021) were also examined. Established Sternbach and Hunter diagnostic criteria were used for formal determination of SS.

Results

Of 6,004 lasmiditan-treated clinical trial patients, 15 reported ≥1 treatment-emergent adverse event consistent with signs and symptom(s) of SS. After review, one case met Sternbach and Hunter criteria, two cases potentially met Sternbach criteria, and three cases reported as SS had limited/no information to determine if either criterion was met. During post-marketing surveillance (approximately 13,400 lasmiditan prescriptions), 17 cases with symptom complexes consistent with SS were reported; 3/17 cases had adequate case descriptions to apply predefined criteria. Of these, two met Sternbach and Hunter criteria, and one met Sternbach criteria.

Conclusion

Awareness of clinical symptomatology and diagnostic criteria of SS can help clinicians with recognition of rare instances of SS that may occur with lasmiditan.

Clinical trial registration

NCT03670810, NCT00384774, NCT00883051, NCT02565186.
3D U-Net for automated detection of multiple sclerosis lesions: utility of transfer learning from other pathologies
Authors: Wahlig Stephen G. , Nedelec Pierre , Weiss David A. , Rudie Jeffrey D. , Sugrue Leo P. , Rauschecker Andreas M.
Published: October 2023

Background and purpose

Deep learning algorithms for segmentation of multiple sclerosis (MS) plaques generally require training on large datasets. This manuscript evaluates the effect of transfer learning from segmentation of another pathology to facilitate use of smaller MS-specific training datasets. That is, a model trained for detection of one type of pathology was re-trained to identify MS lesions and active demyelination.

Materials and methods

In this retrospective study using MRI exams from 149 patients spanning 4/18/2014 to 7/8/2021, 3D convolutional neural networks were trained with a variable number of manually-segmented MS studies. Models were trained for FLAIR lesion segmentation at a single timepoint, new FLAIR lesion segmentation comparing two timepoints, and enhancing (actively demyelinating) lesion segmentation on T1 post-contrast imaging. Models were trained either de-novo or fine-tuned with transfer learning applied to a pre-existing model initially trained on non-MS data. Performance was evaluated with lesionwise sensitivity and positive predictive value (PPV).

Results

For single timepoint FLAIR lesion segmentation with 10 training studies, a fine-tuned model demonstrated improved performance [lesionwise sensitivity 0.55 ± 0.02 (mean ± standard error), PPV 0.66 ± 0.02] compared to a de-novo model (sensitivity 0.49 ± 0.02, p = 0.001; PPV 0.32 ± 0.02, p < 0.001). For new lesion segmentation with 30 training studies and their prior comparisons, a fine-tuned model demonstrated similar sensitivity (0.49 ± 0.05) and significantly improved PPV (0.60 ± 0.05) compared to a de-novo model (sensitivity 0.51 ± 0.04, p = 0.437; PPV 0.43 ± 0.04, p = 0.002). For enhancement segmentation with 20 training studies, a fine-tuned model demonstrated significantly improved overall performance (sensitivity 0.74 ± 0.06, PPV 0.69 ± 0.05) compared to a de-novo model (sensitivity 0.44 ± 0.09, p = 0.001; PPV 0.37 ± 0.05, p = 0.001).

Conclusion

By fine-tuning models trained for other disease pathologies with MS-specific data, competitive models identifying existing MS plaques, new MS plaques, and active demyelination can be built with substantially smaller datasets than would otherwise be required to train new models.
Adoption and implementation of produce prescription programs for under-resourced populations: clinic staff perspectives
Authors: Folta Sara C. , Li Zhongyu , Cash Sean B. , Hager Kurt , Zhang Fang Fang
Published: October 2023

Background

Produce prescription programs represent a promising intervention strategy in the healthcare setting to address disparities in diet quality and diet-related chronic disease. The objective of this study was to understand adoption and implementation factors related to these programs that are common across contexts and those that are context-specific.

Methods

In this qualitative case comparison study, we conducted qualitative interviews with eight clinic staff from five primary care “safety net” clinics, identified by a partnering non-profit organization that operated the programs, in April–July 2021.

Results

Across clinics, the ability to provide a tangible benefit to patients was a key factor in adoption. Flexibility in integrating into clinic workflows was a facilitator of implementation. Fit with usual operations varied across clinics. Common challenges were the need for changes to the workflow and extra staff time. Clinic staff were skeptical about the sustainability of both the benefits to patients and the ability to continue the program at their clinics.

Discussion

This study adds to a growing body of knowledge on the adoption and implementation of produce prescription programs. Future research will further this understanding, providing the evidence necessary to guide adopting clinics and to make informed policy decisions to best promote the growth and financial sustainability of these programs.
Impact of food-based fortification on nutritional outcomes and acceptability in older adults: systematic literature review
Authors: Geny Alexia , Petitjean Maité , Van Wymelbeke-Delannoy Virginie , Sulmont-Rossé Claire
Published: October 2023

Background

“Do it yourself” (DIY) food-based fortification involves adding fortificants into everyday foods. It is a flexible solution that allows older people with reduced appetite to meet their nutritional needs.

Objectives

The aims of the systematic review are (a) to describe DIY fortified recipes, (b) to evaluate their acceptability, and (c) to evaluate whether they are effective levers to improve nutritional outcomes in older people.

Methods

A systematic search of 3 databases (Web of Science, PubMed, Scopus, last searched on January 2022) was undertaken. Main eligibility criteria include older adults aged ≥60 years living at home, in an institution or in hospital. Studies carried out for a specific medical condition or targeting only micronutrient fortification were excluded. After reviewing all titles/abstracts then full-text papers, key data were extracted and synthesized narratively. The quality of included studies was assessed using Kmet et al.

Results

Of 21,493 papers extracted, 44 original studies were included (3,384 participants), with 31 reporting nutritional outcomes, 3 reporting acceptability outcomes and 10 reporting both nutritional and acceptability outcomes. The review highlighted a wide variety of DIY fortified recipes, with additional energy ranging from 23 to 850 kcal/d (M = 403; SE = 62) and/or protein ranging from 4 to 40 g/d (M = 19; SE = 2). Compared to a standard diet, DIY fortification seems to be a valuable strategy for increasing energy and protein intake in older people. However, no strong evidence was observed on the nutritional status.

Implication for future

Further acceptability studies are crucial to ensure that DIY fortified foods are palatable and thus have a significant impact on the nutritional status. In addition, it would be useful for studies to better describe DIY recipes. This information would result in a better understanding of the factors that maximize the impact of DIY fortification on nutritional outcomes. Study registration: PROSPERO no. CRD42021244689.

Systematic review registration: PROSPERO: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021244689.
Probiotics for the prevention and treatment of COVID-19: a rapid systematic review and meta-analysis
Authors: Sohail Aruba , Cheema Huzaifa Ahmad , Mithani Maidah Sohail , Shahid Abia , Nawaz Ahmad , Hermis Alaa Hamza , Chinnam Sampath , Nashwan Abdulqadir J. , Cherrez-Ojeda Ivan , Awan Rehmat Ullah , Ahmad Sharjeel
Published: October 2023

Background

Although numerous modalities are currently in use for the treatment and prophylaxis of COVID-19, probiotics are a cost-effective alternative that could be used in diverse clinical settings. Hence, we conducted a meta-analysis to investigate the role of probiotics in preventing and treating COVID-19 infection.

Methods

We searched several databases from inception to 30 May 2023 for all randomized controlled trials (RCTs) and comparative observational studies that evaluated probiotics (irrespective of the regimen) for the treatment or prevention of COVID-19. We conducted our meta-analysis using RevMan 5.4 with risk ratio (RR) and mean difference (MD) as the effect measures.

Results

A total of 18 studies (11 RCTs and 7 observational studies) were included in our review. Probiotics reduced the risk of mortality (RR 0.40; 95% CI: 0.25–0.65, I2 = 0%). Probiotics also decreased the length of hospital stay, rate of no recovery, and time to recovery. However, probiotics had no effect on the rates of ICU admission. When used prophylactically, probiotics did not decrease the incidence of COVID-19 cases (RR 0.65; 95% CI: 0.37–1.12; I2 = 66%). The results for all outcomes were consistent across the subgroups of RCTs and observational studies (P for interaction >0.05).

Conclusion

The results of this meta-analysis support the use of probiotics as an adjunct treatment for reducing the risk of mortality or improving other clinical outcomes in patients with COVID-19. However, probiotics are not useful as a prophylactic measure against COVID-19. Large-scale RCTs are still warranted for determining the most efficacious and safe probiotic strains.

Systematic Review Registration

PROSPERO (CRD42023390275: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=390275).
Remission and long-term remission of pediatric-onset systemic lupus erythematosus
Authors: Chen Yi-Chieh , Hsu Chiann-Yi , Tsai Ming-Chin , Fu Lin-Shien , Huang Yung-Chieh
Published: October 2023

Objectives

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with diverse clinical presentations and prognoses. Remission can be achieved with or without glucocorticoid (GC) use, and several recent studies have suggested that long-term remission can be achieved in a small portion of patients. Nevertheless, few studies have investigated remission or long-term remission in the pediatric-onset SLE subgroup. This study analyzed the characteristics and factors associated with long-term remission and GC use in pediatric-onset SLE.

Methods

We enrolled 226 patients aged <18 years who received a diagnosis of SLE between January 2006 and December 2016. Three remission condition groups were defined: (A) complete remission, (B) clinical remission off GCs, and (C) clinical remission on GCs. Long-term remission was defined as remission for more than 5 years. We analyzed the treatment durations before remission, durations of remission, and risk factors for non-remission with persistent GC use.

Results

During follow-up, 8 patients (3.5%) achieved complete remission, 35 patients (15.5%) achieved clinical remission off GCs, and 93 patients (41.2%) achieved clinical remission on GCs. In groups A, B, and C, 12.5%, 68.6%, and 65.6% of patients, respectively, remained in remission for >1 year.

Conclusion

This study assessed remission of pediatric-onset SLE. Up to 60.2% of patients had clinical remission after treatment, and 19% of patients achieved remission off GCs. Long-term remission is rarer in pediatric-onset SLE than in adult-onset SLE.
Global expression patterns of R-genes in tomato and potato
Authors: von Dahlen Janina K. , Schulz Kerstin , Nicolai Jessica , Rose Laura E.
Published: October 2023

Introduction

As key-players of plant immunity, the proteins encoded by resistance genes (R-genes) recognize pathogens and initiate pathogen-specific defense responses. The expression of some R-genes carry fitness costs and therefore inducible immune responses are likely advantageous. To what degree inducible resistance driven by R-genes is triggered by pathogen infection is currently an open question.

Methods

In this study we analyzed the expression of 940 R-genes of tomato and potato across 315 transcriptome libraries to investigate how interspecific interactions with microbes influence R-gene expression in plants.

Results

We found that most R-genes are expressed at a low level. A small subset of R-genes had moderate to high levels of expression and were expressed across many independent libraries, irrespective of infection status. These R-genes include members of the class of genes called NRCs (NLR required for cell death). Approximately 10% of all R-genes were differentially expressed during infection and this included both up- and down-regulation. One factor associated with the large differences in R-gene expression was host tissue, reflecting a considerable degree of tissue-specific transcriptional regulation of this class of genes.

Discussion

These results call into question the widespread view that R-gene expression is induced upon pathogen attack. Instead, a small core set of R-genes is constitutively expressed, imparting upon the plant a ready-to-detect and defend status.
Plant species identity and mycorrhizal type explain the root-associated fungal pathogen community assembly of seedlings based on functional traits in a subtropical forest
Authors: Li Yongning , Xie Yan , Liu Zhengjiao , Shi Liuqing , Liu Xubing , Liang Minxia , Yu Shixiao
Published: October 2023

Introduction

As a crucial factor in determining ecosystem functioning, interaction between plants and soil-borne fungal pathogens deserves considerable attention. However, little attention has been paid into the determinants of root-associated fungal pathogens in subtropical seedlings, especially the influence of different mycorrhizal plants.

Methods

Using high-throughput sequencing techniques, we analyzed the root-associated fungal pathogen community for 19 subtropical forest species, including 10 ectomycorrhizal plants and 9 arbuscular mycorrhizal plants. We identified the roles of different factors in determining the root-associated fungal pathogen community. Further, we identified the community assembly process at species and mycorrhizal level and managed to reveal the drivers underlying the community assembly.

Results

We found that plant species identity, plant habitat, and plant mycorrhizal type accounted for the variations in fungal pathogen community composition, with species identity and mycorrhizal type showing dominant effects. The relative importance of different community assembly processes, mainly, homogeneous selection and drift, varied with plant species identity. Interestingly, functional traits associated with acquisitive resource-use strategy tended to promote the relative importance of homogeneous selection, while traits associated with conservative resource-use strategy showed converse effect. Drift showed the opposite relationships with functional traits compared with homogeneous selection. Notably, the relative importance of different community assembly processes was not structured by plant phylogeny. Drift was stronger in the pathogen community for ectomycorrhizal plants with more conservative traits, suggesting the predominant role of stochastic gain and loss in the community assembly.

Discussion

Our work demonstrates the determinants of root-associated fungal pathogens, addressing the important roles of plant species identity and plant mycorrhizal type. Furthermore, we explored the community assembly mechanisms of root-associated pathogens and stressed the determinant roles of functional traits, especially leaf phosphorus content (LP), root nitrogen content (RN) and root tissue density (RTD), at species and mycorrhizal type levels, offering new perspectives on the microbial dynamics underlying ecosystem functioning.
Realized genomic selection across generations in a reciprocal recurrent selection breeding program of Eucalyptus hybrids
Authors: Simiqueli Guilherme Ferreira , Resende Rafael Tassinari , Takahashi Elizabete Keiko , de Sousa João Edesio , Grattapaglia Dario
Published: October 2023

Introduction

Genomic selection (GS) experiments in forest trees have largely reported estimates of predictive abilities from cross-validation among individuals in the same breeding generation. In such conditions, no effects of recombination, selection, drift, and environmental changes are accounted for. Here, we assessed the effectively realized predictive ability (RPA) for volume growth at harvest age by GS across generations in an operational reciprocal recurrent selection (RRS) program of hybrid Eucalyptus.

Methods

Genomic best linear unbiased prediction with additive (GBLUP_G), additive plus dominance (GBLUP_G+D), and additive single-step (HBLUP) models were trained with different combinations of growth data of hybrids and pure species individuals (N = 17,462) of the G1 generation, 1,944 of which were genotyped with ~16,000 SNPs from SNP arrays. The hybrid G2 progeny trial (HPT267) was the GS target, with 1,400 selection candidates, 197 of which were genotyped still at the seedling stage, and genomically predicted for their breeding and genotypic values at the operational harvest age (6 years). Seedlings were then grown to harvest and measured, and their pedigree-based breeding and genotypic values were compared to their originally predicted genomic counterparts.

Results

Genomic RPAs ≥0.80 were obtained as the genetic relatedness between G1 and G2 increased, especially when the direct parents of selection candidates were used in training. GBLUP_G+D reached RPAs ≥0.70 only when hybrid or pure species data of G1 were included in training. HBLUP was only marginally better than GBLUP. Correlations ≥0.80 were obtained between pedigree and genomic individual ranks. Rank coincidence of the top 2.5% selections was the highest for GBLUP_G (45% to 60%) compared to GBLUP_G+D. To advance the pure species RRS populations, GS models were best when trained on pure species than hybrid data, and HBLUP yielded ~20% higher predictive abilities than GBLUP, but was not better than ABLUP for ungenotyped trees.

Discussion

We demonstrate that genomic data effectively enable accurate ranking of eucalypt hybrid seedlings for their yet-to-be observed volume growth at harvest age. Our results support a two-stage GS approach involving family selection by average genomic breeding value, followed by within-top-families individual GS, significantly increasing selection intensity, optimizing genotyping costs, and accelerating RRS breeding.
Simple cryopreservation protocol for Luffa pollen: enhancing breeding efficiency
Authors: Nagar Arvind , Gowthami Ravi , Sureja Amish Kumar , Munshi Anilabha Das , Verma Manjusha , Singh Awani Kumar , Mallick Niharika , Singh Jogendra , Chander Subhash , Shankar Muthusamy , Pathania Pooja , Rajkumar Subramani
Published: October 2023

This study aimed to develop a long-term pollen storage protocol for Luffa species (L. acutangula, L. cylindrica, L. echinata, and L. graveolens) and assess its potential for crop improvement. The optimal medium for in vitro pollen germination varied by species, with Brewbaker and Kwack (BK) medium with 10% sucrose suitable for L. acutangula, L. cylindrica, and L. echinata, and BK medium with 3% sucrose ideal for L. graveolens. Overestimation in staining tests compared to in vitro pollen germination was observed. The best results for cryopreservation were achieved with desiccation periods of 20, 30, and 40 min, maintaining moisture content between 14.04% and 18.55%. Pollen viability was negatively correlated with storage temperature (25, 4, and −20°C) and duration. Cryopreserved pollen at −196°C exhibited the highest viability over a prolonged period (2 months) and was comparable to fresh pollen in terms of germination, ovule fertilization, and fruit and seed set. This study presents a simple and reproducible pollen cryopreservation protocol applicable across Luffa species, facilitating long-term storage and its use in crop improvement efforts.