bluuebunny/crossref_metadata_2025 huggingface dataset:
The International Society of Blood Transfusion (ISBT) Public Health Research Toolkit: A report from the Surveillance, Risk Assessment and Policy Sub‐group of the ISBT Transfusion Transmitted Infectious Diseases Working Party
Authors: Stanley Jean , Busch Michael P. , Erikstrup Christian , Galel Susan A. , Holmberg Jerry A. , Lewin Antoine , O'Brien Sheila F. , Osiowy Carla , Patidar Gopal , Russell W. Alton , Spencer Bryan R. , Higgs Connie ,   the Surveillance, Risk Assessment, Policy Sub‐group of the ISBT Transfusion Transmitted Infectious Diseases Working Party
Published: July 2024

Background and Objectives

Data provided from blood donors have contributed to the understanding of public health epidemiology and policy decisions. A recent example was during the severe acute respiratory syndrome‐related coronavirus (SARS‐CoV‐2) pandemic when blood services monitored the seroprevalence in blood donors. Based on this experience, blood services have the opportunity to expand their role and participate in public health surveillance and research. The aim of this report is to share available resources to assist blood services in this area.

Materials and Methods

The Surveillance, Risk Assessment and Policy (SRAP) Sub‐group of the International Society of Blood Transfusion (ISBT) Transfusion Transmitted Infectious Diseases (TTID) Working Party developed a Public Health Research Toolkit to assist blood services and researchers interested in expanding their role in public health research.

Results

The ISBT Public Health Research Toolkit provides resources for what blood services can offer to public health, examples of donor research studies, the utility of donor data and website links to public health agencies. The toolkit includes a customizable template for those interested in establishing and managing a biobank.

Conclusion

The ISBT Public Health Research Toolkit includes resources to increase the recognition of the role blood donors can play in public health and to help blood services gain commitment and funding from various agencies for new research and surveillance.
Orthoflavivirus surveillance in the Netherlands: Insights from a serosurvey in horses & dogs and a questionnaire among horse owners
Authors: Streng Kiki , Hakze‐van der Honing Renate W. , Graham Heather , van Oort Sophie , de Best Pauline A. , Abourashed Ayat , van der Poel Wim H. M.
Published: July 2024

Aims

Zoonotic arboviruses (arthropod‐borne) of the Orthoflavivirus genus, such as West Nile virus (WNV), Usutu virus (USUV) and Tick‐borne encephalitis virus (TBEV), are emerging in Northwestern Europe and pose a threat to both human and animal health. In the Netherlands, passive symptomatic surveillance (notification of clinical cases) in horses is one of the main pillars for the early detection of WNV. For such passive surveillance to work properly, horse owners and veterinarians need to recognize symptoms and report suspected cases to the authorities. Currently, little is known about the seroprevalence of orthoflaviviruses in domestic animals in the Netherlands. Therefore, this study aims at identifying the seroprevalence of WNV and USUV in horses and dogs in the Netherlands. Additionally, this study seeks to evaluate the knowledge and perceptions of Dutch horse owners towards mosquito‐borne viruses.

Methods and Results

A cross‐sectional serosurvey in horses and dogs was conducted between May 2021 and May 2022. Serum samples were screened using an ELISA and doubtful and positive samples were confirmed by Virus Neutralization Tests for WNV, USUV and TBEV. A validated questionnaire, the MosquitoWise survey, was used to assess the knowledge and perceptions of Dutch horse owners towards mosquito‐borne viruses between July and October 2022. The serosurvey revealed a low seroprevalence for WNV in horses and no WNV‐positive dogs were found. Similarly, a low USUV seroprevalence was found in dogs. The MosquitoWise survey revealed a high knowledge level for horse owners and high awareness of WNV vaccination but a more limited intent to vaccinate.

Conclusions

The low seroprevalences of WNV and USUV indicate many dogs and horses remain susceptible, offering opportunities for trend analysis and surveillance. However, despite multiple recent detections of WNV, USUV, and TBEV in humans, the role of dogs and horses in early detection of human cases is debatable. High awareness among horse owners and the absence of detected equine WNV cases highlight this uncertainty. Continued surveillance is crucial for detecting increased virus circulation and protecting both animal and human health.
Acute intermittent hypoxia increases maximal motor unit discharge rates in people with chronic incomplete spinal cord injury
Authors: Pearcey Gregory E. P. , Afsharipour Babak , Holobar Aleš , Sandhu Milap S. , Rymer W. Zev
Published: July 2024

Acute intermittent hypoxia (AIH) is an emerging technique for enhancing neuroplasticity and motor function in respiratory and limb musculature. Thus far, AIH‐induced improvements in strength have been reported for upper and lower limb muscles after chronic incomplete cervical spinal cord injury (iSCI), but the underlying mechanisms have been elusive. We used high‐density surface EMG (HDsEMG) to determine if motor unit discharge behaviour is altered after 15 × 60 s exposures to 9% inspired oxygen, interspersed with 21% inspired oxygen (AIH), compared to breathing only 21% air (SHAM). We recorded HDsEMG from the biceps and triceps brachii of seven individuals with iSCI during maximal elbow flexion and extension contractions, and motor unit spike trains were identified using convolutive blind source separation. After AIH, elbow flexion and extension torque increased by 54% and 59% from baseline (P = 0.003), respectively, whereas there was no change after SHAM. Across muscles, motor unit discharge rates increased by ∼4 pulses per second (P = 0.002) during maximal efforts, from before to after AIH. These results suggest that excitability and/or activation of spinal motoneurons is augmented after AIH, providing a mechanism to explain AIH‐induced increases in voluntary strength. Pending validation, AIH may be helpful in conjunction with other therapies to enhance rehabilitation outcomes after incomplete spinal cord injury, due to these enhancements in motor unit function and strength.

image

Key points

Acute intermittent hypoxia (AIH) causes increases in muscular strength and neuroplasticity in people living with chronic incomplete spinal cord injury (SCI), but how it affects motor unit discharge rates is unknown.

Motor unit spike times were identified from high‐density surface electromyograms during maximal voluntary contractions and tracked from before to after AIH.

Motor unit discharge rates were increased following AIH.

These findings suggest that AIH can facilitate motoneuron function in people with incomplete SCI.
Effects of Fines Migration and Reservoir Heterogeneity on Well Productivity: Analytical Model and Field Cases
Authors: Russell T. , Nguyen C. , Loi G. , Mohd Shafian S. R. , Zulkifli N. N. , Zeinijahromi A. , Bedrikovetsky P.
Published: July 2024

Formation damage due to fines migration after water breakthrough during oil and gas production results in significant well productivity decline. A recent study derived an analytical model for fines migration during commingled water–oil production in homogeneous reservoirs. Yet, reservoir heterogeneity highly affects formation damage and well productivity. This article develops an analytical model for layer-cake reservoirs. We develop a novel methodology for characterizing productivity decline by considering the impedance as a function of water-cut, two quantities that are commonly measured throughout the production life of the well. The methodology is based on a new analytical model for inflow performance in layer-cake reservoirs under fines migration. The new model integrates pseudo-phase-permeability functions for commingled water–oil production with equations for fines release and induced permeability damage. The analytical model reveals linear well impedance growth versus water-cut increase, where the slope is determined by a modified form of the mobility ratio which includes the extent of formation damage. This linear form is shown to arise when the formation damage factor is constant, regardless of the distribution of reservoir permeabilities. The model is validated by comparison with production histories of five wells from three fields, which exhibit good agreement with the linear trend predicted by the new model. The explicit formulae allows for the prediction of productivity at abandonment, determining the optimal well stimulation time, as well as reconstructing skin values during the early stages of production to better estimate the influences of other formation damage factors, like those induced during drilling and completion.
A Proposed Method and Case Study of Waste Heat Recovery in an Industrial Application
Authors: Wechs Nikolaus , Floss Alexander G. , Tiller Dale K.
Published: July 2024

Waste heat recovered from a refrigeration machine is associated with the double benefit of generating cold and heat with just one unit. Additional energy is required in most cases to achieve these benefits. To evaluate the efficiency of waste heat recovery, two novel efficiency indicators are described. The overhead coefficient of performance (OCOP) describes additional electrical power required to raise the temperature to make waste heat usable. The coefficient of savings describes power reduction when condenser heat is fed into a cold district heating network instead of exhausting it to high-temperature outside air. Results are reported from a case study in a food logistic center with high cooling demand in Isny, Germany. Waste heat at this facility was previously released unused to outside air. We describe how this waste heat can be used to supply sustainable heat supply to a new residential area. During the design phase, it is difficult to choose the best operating temperature for district heating networks (DHNs). The novel indicators are used to value the effort to make waste heat usable. Whereas a supply temperature of 20 °C has no disadvantages for the operator, a supply temperature of 40 °C is associated with an increase in electricity consumption. The resulting OCOPs are above 5.0 even under unfavorable conditions and exceed the theoretically calculated (Holm and Pehnt, 2023, Wärmeschutz und Wärmepumpe-Warum Beides Zusammengehört, Forschungsinstitut für Wärmeschutz e.V., Institut für Energie und Umweltforschung, München/Berlin/Heidelberg, p, 13, 14; Agora Energiewende, Fraunhofer IEG, 2023, Roll-out von Großwärmepumpen in Deutschland, Strategien für den Markthochlauf in Wärmenetzen und Industrie, Berlin) and measured (Fraunhofer Institut für Solare Energiesysteme, 2020, “Wärmepumpen in Bestandsgebäuden, Ergebnisse aus dem Forschungsprojekt, WP-Smart im Bestand.”) coefficients of performance (COPs) for air-sourced heat pumps. Although using waste heat is not free, it is beneficial when overall efficiency is considered.
Distinct sequential death complexes regulate pyroptosis and IL-1β release in response to
Yersinia
blockade of immune signaling
Authors: Wertman Ronit Schwartz , Yost Winslow , Herrmann Beatrice I. , Bourne Christopher M. , Sorobetea Daniel , Go Christina K. , Saller Benedikt S. , Groß Olaf , Scott Phillip , Rongvaux Anthony , Taabazuing Cornelius Y. , Brodsky Igor E.
Published: July 2024

Pathogen infection of host cells triggers an inflammatory cell death termed pyroptosis via activation of inflammatory caspases. However, blockade of immune signaling kinases by the
Yersinia
virulence factor YopJ triggers cell death involving both apoptotic caspase-8 and pyroptotic caspase-1. While caspase-1 is normally activated within inflammasomes,
Yersinia
-induced caspase-1 activation is independent of known inflammasome components. We report that caspase-8 is an essential initiator, while caspase-1 is an essential amplifier of its own activation through two feed-forward loops involving caspase-1 auto-processing and caspase-1–dependent activation of gasdermin D and NLPR3. Notably, while
Yersinia-
induced caspase-1 activation and cell death are inflammasome-independent, IL-1β release requires NLPR3 inflammasome activation. Mechanistically, caspase-8 is rapidly activated within multiple foci throughout the cell, followed by assembly of a canonical inflammasome speck, indicating that caspase-8 and canonical inflammasome complex assemblies are kinetically and spatially distinct. Our findings reveal that functionally interconnected but distinct death complexes mediate pyroptosis and IL-1β release in response to pathogen blockade of immune signaling.
Superstrong, sustainable, origami wood paper enabled by dual-phase nanostructure regulation in cell walls
Authors: Tang Jianfu , Wu Lianping , Fan Xueqin , Dong Xiaofei , Li Xueqi , Xie Yanjun , Li Jian , Rao Jiancun , Li Teng , Gan Wentao
Published: July 2024

Constructing a crystalline-amorphous hybrid structure is an effective strategy to overcome the conflict between the strength and toughness of materials. However, achieving such a material structure often involves complex, energy-intensive processing. Here, we leverage the natural wood featuring coexisting crystalline and amorphous regions to achieve superstrong and ultratough wood paper (W-paper) via a dual-phase nanostructure regulation strategy. After partially removing amorphous hemicellulose and eliminating most lignin, the treated wood can self-densify through an energy-efficient air drying, resulting in a W-paper with high tensile strength, toughness, and folding endurance. Coarse-grained molecular dynamics simulations reveal the underlying deformation mechanism of the crystalline and amorphous regions inside cell walls and the failure mechanism of the W-paper under tension. Life cycle assessment reveals that W-paper shows a lower environmental impact than commercial paper and common plastics. This dual-phase nanostructure regulation based on natural wood may provide valuable insights for developing high-performance and sustainable film materials.
The long-lasting effect of armed conflicts deaths on the living: Quantifying family bereavement
Authors: Alburez-Gutierrez Diego , Acosta Enrique , Zagheni Emilio , Williams Nathalie E.
Published: July 2024

Armed conflicts escalate combatant and civilian mortality and produce considerable levels of family bereavement. Yet, we know little about the prevalence of bereavement in conflict-affected populations. The violent loss of kin affects individuals across several dimensions, including trauma, mental health, socioeconomic status, and caregiving, especially during childhood and old age. Here, we propose a method to quantify population-level loss of parents and offspring in conflict-affected populations. Our analyses demonstrate that bereavement levels consistently surpass fatality rates in 16 conflict-affected settings. Using demographic projections, we show that these populations will continue to experience considerable levels of bereavement in the coming decades, independent of the future development of the respective conflicts. This quantification underscores bereavement as a profound yet understudied consequence of conflict with potentially far-reaching implications lingering long after the conflict’s end.
Recurrently gellable and thermochromic inorganic hydrogel thermogalvanic cells
Authors: Liu Youfa , Chen Xiaoyang , Dong Xiaoyu , Liu Ao , Ouyang Kefeng , Huang Yan
Published: July 2024

Thermogalvanic cells (TGCs) draw great attention in the field of heat to electricity conversion, but TGCs were only in the form of liquid or organic gel. Here, we report an all-inorganic hydrogel TGC via simply mixing and stirring two inorganic salt solutions. Benefiting from the hydrogen bonds resultant framework and endogenous Fe
2+/3+
redox couple, the TGC can recurrently pulverize-gel with completely holding its initial thermogalvanic performances after even 60 cycles. As the temperature and pH coregulating Fe
3+
concentration and reversible transformation between Fe
3+
and Fe(OH)
3
, we boost thermopower and realize thermochromism. This work provides a different perspective for TGCs and offers an avenue for future hydrogel materials research.
Microbiota diversity and anti-
Pseudogymnoascus destructans
bacteria isolated from
Myotis pilosus
skin during late hibernation
Authors: Lu Yaping , Ren Huilan , Li Zhongle , Leng Haixia , Li Aoqiang , Dai Wentao , Huang Long , Feng Jiang , Sun Keping
Published: July 2024

Symbiotic microorganisms that reside on the host skin serve as the primary defense against pathogens in vertebrates. Specifically, the skin microbiome of bats may play a crucial role in providing resistance against
Pseudogymnoascus destructans
(
Pd
), the pathogen causing white-nose syndrome. However, the epidermis symbiotic microbiome and its specific role in resisting
Pd
in highly resistant bats in Asia are still not well understood. In this study, we collected and characterized skin microbiota samples of 19
Myotis pilosus
in China and explored the differences between
Pd
-positive and negative individuals. We identified inhibitory effects of these bacteria through cultivation methods. Our results revealed that the Simpson diversity index of the skin microbiota for positive individuals was significantly lower than that of negative individuals, and the relative abundance of
Pseudomonas
was significantly higher in positive bats. Regardless of whether individuals were positive or negative for
Pd
, the relative abundance of potentially antifungal genera in skin microbiota was high. Moreover, we successfully isolated 165 microbes from bat skin and 41 isolates from positive individuals able to inhibit
Pd
growth compared to only 12 isolates from negative individuals. A total of 10 genera of
Pd
-inhibiting bacteria were screened, among which the genera
Algoriella
,
Glutamicibacter
, and
Psychrobacter
were newly discovered as
Pd
-inhibiting genera. These
Pd
-inhibiting bacteria metabolized a variety of volatile compounds, including dimethyl trisulfide, dimethyl disulfide, propylene sulfide, 2-undecanone, and 2-nonanone, which were able to completely inhibit
Pd
growth at low concentrations.

IMPORTANCE

Recently, white-nose syndrome has caused the deaths of millions of hibernating bats, even threatening some with regional extinction. Bats in China with high resistance to
Pseudogymnoascus destructans
can provide a powerful reference for studying the management of white-nose syndrome and understanding the bats against the pathogen’s intrinsic mechanisms. This study sheds light on the crucial role of host symbiotic skin microorganisms in resistance to pathogenic fungi and highlights the potential for harnessing natural defense mechanisms for the prevention and treatment of white-nose syndrome. In addition, this may also provide promising candidates for the development of bioinsecticides and fungicides that offer new avenues for addressing fungal diseases in wildlife and agricultural environments.
mSphere of Influence: Predicting the evolution of pathogen populations
Authors: Mortimer Tatum D.
Published: July 2024

Tatum D. Mortimer works in the field of pathogen population genomics and evolution. In this mSphere of Influence article, she reflects on how “Frequency-dependent selection can forecast evolution in
Streptococcus pneumoniae
” by Azarian et al. and “Contingency, repeatability, and predictability in the evolution of a prokaryotic pangenome” by Beavan et al. made an impact on her by highlighting the ways in which genomic data can be used to predict pathogen evolution.
Learning metabolic dynamics from irregular observations by Bidirectional Time-Series State Transfer Network
Authors: Xu Shaohua , Xu Ting , Yang Yuping , Chen Xin
Published: July 2024

Modeling microbial metabolic dynamics is important for the rational optimization of both biosynthetic systems and industrial processes to facilitate green and efficient biomanufacturing. Classical approaches utilize explicit equation systems to represent metabolic networks, enabling the quantification of pathway fluxes to identify metabolic bottlenecks. However, these white-box models, despite their diverse applications, have limitations in simulating metabolic dynamics and are intrinsically inaccurate for industrial strains that lack information on network structures and kinetic parameters. On the other hand, black-box models do not rely on prior mechanistic knowledge of strains but are built upon observed time-series trajectories of biosynthetic systems in action. In practice, these observations are typically irregular, with discontinuously observed time points across multiple independent batches, each time point potentially containing missing measurements. Learning from such irregular data remains challenging for existing approaches. To address this issue, we present the Bidirectional Time-Series State Transfer Network (BTSTN) for modeling metabolic dynamics directly from irregular observations. Using evaluation data sets derived from both ideal dynamic systems and a real-world fermentation process, we demonstrate that BTSTN accurately reconstructs dynamic behaviors and predicts future trajectories. This approach exhibits enhanced robustness against missing measurements and noise, as compared to the state-of-the-art methods.

IMPORTANCE

Industrial biosynthetic systems often involve strains with unclear genetic backgrounds, posing challenges in modeling their distinct metabolic dynamics. In such scenarios, white-box models, which commonly rely on inferred networks, are thereby of limited applicability and accuracy. In contrast, black-box models, such as statistical models and neural networks, are directly fitted or learned from observed time-series trajectories of biosynthetic systems in action. These methods typically assume regular observations without missing time points or measurements. If the observations are irregular, a pre-processing step becomes necessary to obtain a fully filled data set for subsequent model training, which, at the same time, inevitably introduces errors into the resulting models. BTSTN is a novel approach that natively learns from irregular observations. This distinctive feature makes it a unique addition to the current arsenal of technologies modeling metabolic dynamics.
Salinity reconstruction in Proterozoic depositional systems
Authors: Liu Zhanhong , Algeo Thomas J. , Brocks Jochen J. , van Maldegem Lennart M. , Gilleaudeau Geoffrey J. , Kah Linda C. , Cheng Meng , Yu Wenchao
Published: July 2024

Although elemental proxies (i.e., boron/gallium [B/Ga], strontium/barium [Sr/Ba], and sulfur/total organic carbon [S/TOC]) have been extensively used to evaluate paleo-watermass salinities in Phanerozoic shales and marls, their application to Precambrian-age formations has been limited. Here, we evaluate these proxies for five depositional systems ranging in age from late Paleoproterozoic to late Neoproterozoic. Our analysis shows that the range of B/Ga ratios encountered (~2–9) matches that seen in Phanerozoic deposits and is consistent with a spectrum of salinity conditions ranging from freshwater (B/Ga < 3) to brackish (B/Ga 3–6) to marine (B/Ga 6–12). Furthermore, all B/Ga-based salinity assignments are consistent with existing paleosalinity inferences, including fully marine conditions for the ca. 650 Ma Areyonga-Aralka and ca. 1640 Ma Barney Creek formations in Australia, mixed brackish-marine conditions for the ca. 650 Ma Datangpo Formation in China and the ca. 1100 Ma El Mreiti Group shales in Mauritania, and low-brackish conditions for the ca. 1080 Ma Nonesuch Formation in North America. Our salinity assessment for the Nonesuch Formation is particularly significant in view of extended debate regarding the lacustrine versus marine character of this unit. The influences of diagenesis and clay-mineral assemblages on B/Ga-based salinity interpretations are generally minor to insignificant. The Sr/Ba proxy yielded systematically lower salinity estimates than the B/Ga proxy based on salinity facies thresholds established from modern aqueous systems, a pattern that we interpret to reflect reduced Sr concentrations in Proterozoic seawater. The S content and S/TOC ratios of all units are sufficiently high as to preclude freshwater conditions (incidentally indicating that Proterozoic seawater sulfate concentrations were higher than sometimes inferred). These findings demonstrate that elemental salinity proxies, especially B/Ga, are broadly applicable to shale formations of Proterozoic age, providing an important new tool for paleoenvironmental analysis that has the potential to reshape our understanding of life-environment co-evolution in deep-time systems.
Petrocella pelovolcani sp. nov., an Alkaliphilic Anaerobic Bacterium Isolated from Terrestrial Mud Volcano
Authors: Frolova A. A. , Merkel A. Yu. , Kopitsyn D. S. , Slobodkin A. I.
Published: July 2024

Diversity of extremophilic microorganisms in mud volcanoes is largely unexplored. Here we report the isolation of a novel alkaliphilic, mesophilic, fermentative bacterium (strain FN5sucT) from a terrestrial mud volcano located at the Taman Peninsula, Russia. Cells of strain FN5sucT are gram-stain-positive, non-sporeforming, motile rods. The temperature range for growth is 10–37°C, with an optimum at 30°C. The pH range for growth is 7.5–10.0, with an optimum at pH 9.0. The isolate utilizes various organic polymeric substances, organic acids, carbohydrates, and proteinaceous compounds. The end products of carbohydrates fermentation are acetate, CO2 and trace amounts of H2 and formate. The major cellular fatty acid compounds are C16:0, C16:1 ω7c, and monounsaturated dimethyl acetal C14:1. Phylogenetic analysis reveals that strain FN5sucT is most closely related to Petrocella atlantisensis = DSM 105309T (98.4% 16S rRNA gene identity). The total size of the genome of strain FN5sucT is 3.35 Mb, and a genomic DNA G+C content is 37.0 mol %. The genome contains complete glycolisis/glyconeogenesis pathway. We propose to assign strain FN5sucT to the genus Petrocella, as a new species, Petrocella pelovolcani sp. nov. The type strain is FN5sucT (=DSM 113898T = UQM 41591T).
Ileo-ileal intussusception secondary to a Peutz-Jeghers hamartomatous polyp in an infant
Authors: Neville Jonathan J , Ellul Sarah , Healy Costa
Published: July 2024

We report the case of ileo-ileal intussusception secondary to a Peutz-Jeghers syndrome (PJS) hamartomatous polyp in a male infant. The patient presented with non-bilious vomiting and a single episode of passing blood in his stool. An upper gastrointestinal contrast study showed proximal bowel obstruction. At laparotomy, ileo-ileal intussusception was identified with a papillary mass acting as a lead point. The mass was resected, and a primary anastomosis was performed. The patient recovered well and was discharged on postoperative day 5. Histological assessment diagnosed a PJS hamartoma. The patient was well at 1 month follow-up. This case report describes a rare cause of intussusception in an infant that should be considered in the differential diagnosis. The diagnosis of PJS in infancy is uncommon and requires long-term follow-up.
Patient safety in actioning and communicating blood test results in primary care: a UK wide audit using the Primary care Academic CollaboraTive (PACT)
Authors: Watson Jessica , Duncan Polly , Burrell Alexander , Bennett-Britton Ian , Hodgson Sam , Merriel Samuel W D , Waqar Salman , Razumovskaya-Hough Alexandra , Whiting Penny F
Published: July 2024

Background

Errors associated with failures in filing, actioning and communicating blood test results can lead to delayed and missed diagnoses and patient harm. This study aimed to audit how blood tests in primary care are filed, actioned and communicated in primary care, to identify areas for patient safety improvements.

Methods

UK primary care clinicians were recruited through the Primary Care Academic CollaboraTive (PACT). PACT members audited 50 recent sets of blood tests from their practice and retrospectively extracted data on blood test result coding, actioning and communication. PACT members received a practice report, showing their own results, benchmarked against other participating practices.

Results

PACT members from 57 general practices across all four UK nations collected data on 2572 patients who had blood tests in April 2021. In 89.9% (n=2311) they agreed with the initial clinician’s actioning of blood tests; 10.1% disagreed, either partially (7.1%) or fully (3.0%).

In 44% of patients (n=1132) an action (eg, ‘make an appointment’) was specified by the filing clinician. This action was carried out in 89.7% (n=1015/1132) of cases; in 6.8% (n=77) the action was not carried out, in 3.5% (n=40) it was unclear. In the 117 cases where the test result had not been actioned 38% (n=45) were felt to be at low risk of harm, 1.7% (n=2) were at high risk of harm, 0.85% (n=1) came to harm.

Overall, in 47% (n=1210) of patients there was no evidence in the electronic health records that results had been communicated. Out of 1176 patients with one or more abnormal results there was no evidence of test communication in 30.6% (n=360). There were large variations between practices in rates of actioning and communicating tests.

Conclusion

This research demonstrates variation in the way blood test results are actioned and communicated, with important patient safety implications.
Person-centred decisions in emergency care for older people living with frailty: principles and practice
Authors: van Oppen James David , Coats Tim , Conroy Simon , Hayden Sarah , Heeren Pieter , Hullick Carolyn , Liu Shan , Lucke Jacinta , Lukin Bill , McNamara Rosa , Melady Don , Mooijaart Simon P , Rosen Tony , Banerjee Jay
Published: July 2024

Older people living with frailty are frequent users of emergency care and have multiple and complex problems. Typical evidence-based guidelines and protocols provide guidance for the management of single and simple acute issues. Meanwhile, person-centred care orientates interventions around the perspectives of the individual. Using a case vignette, we illustrate the potential pitfalls of applying exclusively either evidence-based or person-centred care in isolation, as this may trigger inappropriate clinical processes or place undue onus on patients and families. We instead advocate for delivering a combined evidence-based, person-centred approach to healthcare which considers the person’s situation and values, apparent problem and available options.
ImmunoPET imaging of LAG-3 expression in tumor microenvironment with68Ga-labelled cyclic peptides tracers: from bench to bedside
Authors: Zhou Ming , Chen Bei , Lu Chenxi , Yang Jinhui , Liu Peng , Wang Xiaobo , Hu Shuo
Published: July 2024

Background

Lymphocyte activation gene 3 (LAG-3) has been considered as the next generation of immune checkpoint and a promising prognostic biomarker of immunotherapy. As with programmed cell death protein-1/programmed death-ligand 1 and cytotoxic T-lymphocyte antigen-4 inhibitors, positron emission tomography (PET) imaging strategies could benefit the development of clinical decision-making of LAG-3-related therapy. In this study, we developed and validated68Ga-labeled cyclic peptides tracers for PET imaging of LAG-3 expression in bench-to-bedside studies.

Methods

A series of LAG-3-targeted cyclic peptides were modified and radiolabeled with68GaCl3and evaluated their affinity and specificity, biodistribution, pharmacokinetics, and radiation dosimetry in vitro and in vivo. Furthermore, hu-PBL-SCID (PBL) mice models were constructed to validate the capacity of [68Ga]Ga-CC09-1 for mapping of LAG-3+lymphocytes infiltrates using longitudinal PET imaging. Lastly, [68Ga]Ga-CC09-1 was translated into the first-in-human studies to assess its safety, biodistribution and potential for imaging of LAG-3 expression.

Results

A series of cyclic peptides targeting LAG-3 were employed as lead compounds to design and develop68Ga-labeled PET tracers. In vitro binding assays showed higher affinity and specificity of [68Ga]Ga-CC09-1 in Chinese hamster ovary-human LAG-3 cells and peripheral blood mononuclear cells. In vivo PET imaging demonstrated better imaging capacity of [68Ga]Ga-CC09-1 with a higher tumor uptake of 1.35±0.33 per cent injected dose per gram and tumor-to-muscle ratio of 17.18±3.20 at 60 min post-injection. Furthermore, [68Ga]Ga-CC09-1 could detect the LAG-3+lymphocyte infiltrates in spleen, lung and salivary gland of PBL mice. In patients with melanoma and non-small cell lung cancer, primary lesions with modest tumor uptake were observed in [68Ga]Ga-CC09-1 PET, as compared with that of [18F]FDG PET. More importantly, [68Ga]Ga-CC09-1 delineated the heterogeneity of LAG-3 expression within large tumors.

Conclusion

These findings consolidated that [68Ga]Ga-CC09-1 is a promising PET tracer for quantifying the LAG-3 expression in tumor microenvironment, indicating its potential as a companion diagnostic for patients stratification and therapeutic response monitoring in anti-LAG-3 therapy.
Motherhood, medicine and magazines in interwar Vienna: the case ofDie Mutter(The Mother, 1924–1926)
Authors: George Alys X
Published: July 2024

In an era long before ‘Doctor Google’, the question of how people accessed information about their bodies and their health is significant. This article investigates how medical knowledge about motherhood was disseminated in the pages of an entirely neglected and short-lived, yet important interwar Viennese periodical,Die Mutter: Halbmonatsschrift für alle Fragen der Schwangerschaft, Säuglingshygiene und Kindererziehung(The Mother: A Biweekly Magazine for All Questions about Pregnancy, Infant Hygiene and Child-Rearing). The magazine’s founder, editor and champion was Gina Kaus, a bestselling, prize-winning author and screenplay writer.Die Mutterwas part of a wider interwar Viennese press landscape of publications dedicated to mothers and motherhood, many of them produced by women for women. I suggest that periodicals about motherhood constituted an important alternative public sphere, one coming in part from the grassroots, rather than from a top-down municipal approach to public health—even in a city where mothers’ bodies were already a focal point for left-of-center politics and public health initiatives in the wake of World War I.
Sensitivity to change of structural outcomes in axial spondyloarthritis after 10 years of follow up. Data from the DESIR cohort
Authors: López-Medina Clementina , Molto Anna , Sepriano Alexandre , Ramiro Sofia , Tournadre Anne , Dougados Maxime
Published: July 2024

Objective

To evaluate the sensitivity to change in structural imaging outcomes over 10 years of follow-up in patients with axial spondyloarthritis (axSpA).

Methods

Patients with axSpA from the Devenir des Spondyloarthropathies Indifferénciées Récentes cohort were included. Radiographs and MRIs of the sacroiliac joints (SIJ) and spine were obtained at baseline and at 1, 2, 5 and 10 years. The yearly rate of change of each structural outcome was analysed using generalised estimating equation models, including all patients with ≥1 score from ≥1 reader from ≥1 reading wave, using the time (years) as an explanatory variable and adjusting for reader and wave. All outcomes were standardised, and the relative standardised rate of change was calculated (ie, the standardised rate of an outcome divided by the rate of a reference outcome).

Results

A total of 659 patients (46% males and mean age 33.6 years) were included. The most sensitive outcome to change in the SIJ (both MRI and radiographs) was the presence of ≥3 fatty lesions at a specific timepoint, with a relative standardised rate of change per year of 5.28 using the modified New York criteria as reference.

Similarly, the most sensitive to change (in both MRI and radiographs) outcome in the spine was the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS; relative standardised yearly change 1.76) using ≥1 syndesmophyte as reference.

Conclusion

MRI structural outcomes in the SIJ (ie, fatty lesions) are more sensitive to change than radiographic outcomes. Conversely, the mSASSS remains the most sensitive method, even when compared with MRI of the spine.
Reframing social media discourse following the FDA’s menthol ban announcement as industry agenda setting rather than public sentiment
Authors: Silver Nathan A , Kierstead Elexis C , Emery Sherry L , Binns Steven , Guy Mignonne C , Schillo Barbara
Published: July 2024

Background

The tobacco industry has spent millions of dollars promoting racialised narratives against the US Food and Drug Administration’s recently announced ban on menthol as a characterising cigarette flavour. This research investigates racialised narratives in online discourse following the ban’s announcement.

Methods

Tweets and users responding to the April 2022 menthol ban announcement were content analysed to examine the influence of tobacco industry affiliates and potentially organic African-American/Black (AA/B) users. Next we investigated the extent to which the menthol ban was discussed on AA/B subreddits and used Latent Dirichlet Allocation topic modelling to provide an overview of the menthol ban discussion on Reddit.

Results

Only 28 (13.9%) tweets by 22 users claimed that the menthol ban would lead to police violence and/or racial discrimination. Of users who tweeted about over-policing, eight (36.4%) had financial connections to the tobacco industry. There were only three tweets receiving a combined seven retweets from potentially organic AA/B users. On Reddit, only two posts with one comment discussed the menthol ban on subreddits dedicated to AA/B issues and culture. Topic modelling showed that the most common topic related to the menthol ban involved the social and political implications of the ban followed by illicit markets and protecting youth.

Conclusion

Tweets claiming a menthol ban will lead to police violence are indicative of industry agenda-setting. The menthol ban was not a prominent topic of discussion in AA/B subreddits although users discussing news and politics expressed concern for how AA/B people would respond to a ban politically.
Totarol exhibits antibacterial effects through antibiofilm and combined interaction against vancomycin-resistant Enterococcus faecalis
Authors: Hyeon Ga-Eun , Eom Yong-Bin
Published: July 2024

The rise of vancomycin-resistant enterococci (VRE) due to antibiotic overuse poses a significant threat to long-term care patients and those with impaired immune systems. Therefore, it is imperative to seek alternatives to overcome multidrug resistance. This study aimed to evaluate totarol, a natural compound derived from Podocarpus totara, for its antibacterial activity against vancomycin-resistant Enterococcus faecalis (VREF). Totarol exhibited potent antibacterial activity at a very low concentration of 0.25 µg/mL and demonstrated antibiofilm effects through biofilm inhibitory concentration and biofilm eradication concentration assays. Confocal laser scanning microscopy confirmed that totarol inhibited not only biofilm mass but also bacterial cell viability. The combinatorial use of sublethal concentrations of totarol and vancomycin showed antibacterial activity, as observed in the time-kill assay. Quantitative polymerase chain reaction assays revealed a concentration-dependent downregulation of key virulence genes ( vanA, ace, asa, efaA, and esp) in VREF when exposed to totarol. In summary, totarol emerges as a promising adjuvant with vancomycin for inhibiting VREF, addressing vancomycin resistance and biofilm formation—critical challenges associated with VRE infection. Since this was an in vitro study, the role of totarol in the clinical implications of VREF treatment remains to be demonstrated.
Fully charmed tetraquark states in $$8_{[c\bar{c}]}\otimes 8_{[c\bar{c}]}$$ color structure via QCD sum rules
Authors: Tang Chun-Meng , Duan Chun-Gui , Tang Liang
Published: July 2024

Stimulated by the recent experimental results on the fully-charm tetraquark states, we systematically calculate the mass spectra of the fully-charm tetraquark states in $$8_{[c\bar{c}]}\otimes 8_{[c\bar{c}]}$$

8

[
c

c

¯

]

⊗

8

[
c

c

¯

]

color configuration via QCD sum rules. By constructing nine $$8_{[c\bar{c}]}\otimes 8_{[c\bar{c}]}$$

8

[
c

c

¯

]

⊗

8

[
c

c

¯

]

type currents with quantum numbers $$J^{PC}=0^{-+},0^{--},1^{-+},1^{+-},1^{--}$$

J

PC

=

0

-
+

,

0

-
-

,

1

-
+

,

1

+
-

,

1

-
-

and $$2^{++}$$

2

+
+

, we perform analytic calculation up to dimension six in the operator product expansion (OPE). We find the fully-charm tetraquark states with $$J^{PC}=1^{+-},2^{++}$$

J

PC

=

1

+
-

,

2

+
+

lie around 6.48 $$\sim $$
∼
6.62 GeV while the fully-charm tetraquark states with $$J^{PC}=0^{-+},0^{--},1^{--},1^{-+}$$

J

PC

=

0

-
+

,

0

-
-

,

1

-
-

,

1

-
+

are about 6.85 $$\sim $$
∼
7.02 GeV. Notably, the mass predictions for the $$c\bar{c}c\bar{c}$$

c

c

¯

c

c

¯

tetraquarks, specifically those with $$J^{PC}=2^{++}$$

J

PC

=

2

+
+

, align with the broad structure identified by LHCb. Moreover, the masses of fully-charm tetraquarks with $$J^{PC}=0^{-+}$$

J

PC

=

0

-
+

and $$1^{-+}$$

1

-
+

are anticipated to match closely with the mass of X(6900), considering the margin of error. Such findings hint at the presence of some $$8_{[c\bar{c}]}\otimes 8_{[c\bar{c}]}$$

8

[
c

c

¯

]

⊗

8

[
c

c

¯

]

components within the di-$$J/\psi $$

J
/
ψ

structures observed by LHCb. The predictions for tetraquark states with $$J^{PC}=0^{--},1^{+-},1^{--}$$

J

PC

=

0

-
-

,

1

+
-

,

1

-
-

may be accessible in the future BelleII, Super-B, PANDA, and LHCb experiments.
Ensemble Deep Learning Technique for Detecting MRI Brain Tumor
Authors: Jader Rasool Fakhir , Kareem Shahab Wahhab , Awla Hoshang Qasim
Published: July 2024

The classification process of MRI (magnetic resonance imaging) is frequently used for making medical diagnoses for conditions including pituitary, glioma, meningioma, and no tumor. For this reason, determining the type of MRI and its quantity are significant and valuable measurements that reveal the brain’s state of health. To segment and classify brain analysis, laboratory personnel employ manual examination via screen; this requires a lot of labour and time. On the other hand, the devices used by specialists are not practical or inexpensive for every doctor or institution. In recent years, a variety of computational algorithms for segmentation and classification have been developed with improved results to get around the issue. Artificial neural networks (ANNs) have the capability and promise to classify in this regard. The purpose of this paper is to create and put into practice a system for classifying different types of MRI images of brain tumor samples. As a result, this paper concentrated on the tasks of segmentation, feature extraction, classifier building, and classification into four categories using various machine learning algorithms. The authors used VGG‐16, ResNet‐50, and AlexNet models based on the transfer learning algorithm for three models to classify images as an ensemble model. As a result, MRI brain tumor segmentation is more precise because each spatial feature point can now refer to all other contextual data. In the specifics, our models outperformed every other published modern ensemble model in the official deep learning challenge without any postprocessing. The ensemble model achieved an accuracy of 99.16%, a sensitivity of 98.47%, a specificity of 98.57%, a precision of 98.74%, a recall of 98.49%, and an F1‐score of 98.18%. These results significantly surpass the accuracy of other methods such as Naive Bayes, decision tree classifier, random forest, and DNN models.
Supplementary Data 2 from Epigenetic Induction of Cancer-Testis Antigens and Endogenous Retroviruses at Single-Cell Level Enhances Immune Recognition and Response in Glioma
Authors: Lai Thomas J. , Sun Lu , Li Kevin , Prins Terry J. , Treger Janet , Li Tie , Sun Matthew Z. , Nathanson David A. , Liau Linda M. , Lai Albert , Prins Robert M. , Everson Richard G.
Published: July 2024

hERV raw counts and FPKM values
Development and Application of Genetic Ancestry Reconstruction Methods to Study Diversity of Patient-Derived Models in the NCI PDXNet Consortium
Authors: Lott Paul C. , Chiu Katherine , Quino Juanita Elizabeth , Vang April Pangia , Lloyd Michael W. , Srivastava Anuj , Chuang Jeffrey H. ,   for the PDXNet Consortium, Carvajal-Carmona Luis G.
Published: July 2024

Precision medicine holds great promise for improving cancer outcomes. Yet, there are large inequities in the demographics of patients from whom genomic data and models, including patient-derived xenografts (PDX), are developed and for whom treatments are optimized. In this study, we developed a genetic ancestry pipeline for the Cancer Genomics Cloud, which we used to assess the diversity of models currently available in the National Cancer Institute–supported PDX Development and Trial Centers Research Network (PDXNet). We showed that there is an under-representation of models derived from patients of non-European ancestry, consistent with other cancer model resources. We discussed these findings in the context of disparities in cancer incidence and outcomes among demographic groups in the US, as well as power analyses for biomarker discovery, to highlight the immediate need for developing models from minority populations to address cancer health equity in precision medicine. Our analyses identified key priority disparity-associated cancer types for which new models should be developed.

Significance:

Understanding whether and how tumor genetic factors drive differences in outcomes among U.S. minority groups is critical to addressing cancer health disparities. Our findings suggest that many additional models will be necessary to understand the genome-driven sources of these disparities.
Role of Cancer Side Population Stem Cells in Ovarian Cancer Angiogenesis
Authors: Pan Yue , Yang XueFen , Chen Miaojuan , Shi Kun , Lyu Yuan , Meeson Annette P. , Lash Gendie E.
Published: July 2024

Ovarian cancer is one of the most common gynecologic malignancies. Recurrence and metastasis often occur after treatment, and it has the highest mortality rate of all gynecological tumors. Cancer stem cells (CSCs) are a small population of cells with the ability of self-renewal, multidirectional differentiation, and infinite proliferation. They have been shown to play an important role in tumor growth, metastasis, drug resistance, and angiogenesis. Ovarian cancer side population (SP) cells, a type of CSC, have been shown to play roles in tumor formation, colony formation, xenograft tumor formation, ascites formation, and tumor metastasis. The rapid progression of tumor angiogenesis is necessary for tumor growth; however, many of the mechanisms driving this process are unclear as is the contribution of CSCs. The aim of this review was to document the current state of knowledge of the molecular mechanism of ovarian cancer stem cells (OCSCs) in regulating tumor angiogenesis.
Intraperitoneal Dedifferentiated Liposarcoma: Unveiling a Rare Diagnosis in Peritoneal Fluid Cytology – A Case Report with Literature Review
Authors: Prabhu Swathi , Monappa Vidya , Kumar Naveena A.N. , Suvarna Nischitha , Godkhindi Vishwapriya Mahadev
Published: July 2024

Introduction: Sarcomas presenting as malignant effusions are rare, and diagnosing them on fluid cytology requires expertise and clinicoradiological correlation as cells undergo morphological changes, mimicking carcinoma or mesothelioma. Case Presentation: We present a case of a 70-year-old man with abdominal distention and pain, initially suggestive of carcinoma on peritoneal fluid cytology. However, subsequent analysis with immunohistochemistry on the cell block revealed diffuse nuclear positivity for MDM2, leading to the diagnosis of dedifferentiated liposarcoma. Conclusion: The cytological diagnosis of dedifferentiated liposarcoma is challenging and requires a high index of suspicion, with clinicoradiological correlation. Utilizing immunohistochemistry on cell block samples enhances diagnostic accuracy and guides appropriate patient management.