bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibrin promotes oxidative stress and neuronal loss in traumatic brain injury via innate immune activation
Authors: Dean Terry , Mendiola Andrew S. , Yan Zhaoqi , Meza-Acevedo Rosa , Cabriga Belinda , Akassoglou Katerina , Ryu Jae Kyu
Published: April 2024

Background

Traumatic brain injury (TBI) causes significant blood-brain barrier (BBB) breakdown, resulting in the extravasation of blood proteins into the brain. The impact of blood proteins, especially fibrinogen, on inflammation and neurodegeneration post-TBI is not fully understood, highlighting a critical gap in our comprehension of TBI pathology and its connection to innate immune activation.

Methods

We combined vascular casting with 3D imaging of solvent-cleared organs (uDISCO) to study the spatial distribution of the blood coagulation protein fibrinogen in large, intact brain volumes and assessed the temporal regulation of the fibrin(ogen) deposition by immunohistochemistry in a murine model of TBI. Fibrin(ogen) deposition and innate immune cell markers were co-localized by immunohistochemistry in mouse and human brains after TBI. We assessed the role of fibrinogen in TBI using unbiased transcriptomics, flow cytometry and immunohistochemistry for innate immune and neuronal markers in Fggγ390–396A knock-in mice, which express a mutant fibrinogen that retains normal clotting function, but lacks the γ390–396 binding motif to CD11b/CD18 integrin receptor.

Results

We show that cerebral fibrinogen deposits were associated with activated innate immune cells in both human and murine TBI. Genetic elimination of fibrin-CD11b interaction reduced peripheral monocyte recruitment and the activation of inflammatory and reactive oxygen species (ROS) gene pathways in microglia and macrophages after TBI. Blockade of the fibrin-CD11b interaction was also protective from oxidative stress damage and cortical loss after TBI.

Conclusions

These data suggest that fibrinogen is a regulator of innate immune activation and neurodegeneration in TBI. Abrogating post-injury neuroinflammation by selective blockade of fibrin’s inflammatory functions may have implications for long-term neurologic recovery following brain trauma.
Validity of an android device for assessing mobility in people with chronic stroke and hemiparesis: a cross-sectional study
Authors: Sánchez-Sánchez M. Luz , Ruescas-Nicolau Maria-Arantzazu , Arnal-Gómez Anna , Iosa Marco , Pérez-Alenda Sofía , Cortés-Amador Sara
Published: April 2024

Background

Incorporating instrument measurements into clinical assessments can improve the accuracy of results when assessing mobility related to activities of daily living. This can assist clinicians in making evidence-based decisions. In this context, kinematic measures are considered essential for the assessment of sensorimotor recovery after stroke. The aim of this study was to assess the validity of using an Android device to evaluate kinematic data during the performance of a standardized mobility test in people with chronic stroke and hemiparesis.

Methods

This is a cross-sectional study including 36 individuals with chronic stroke and hemiparesis and 33 age-matched healthy subjects. A simple smartphone attached to the lumbar spine with an elastic band was used to measure participants’ kinematics during a standardized mobility test by using the inertial sensor embedded in it. This test includes postural control, walking, turning and sitting down, and standing up. Differences between stroke and non-stroke participants in the kinematic parameters obtained after data sensor processing were studied, as well as in the total execution and reaction times. Also, the relationship between the kinematic parameters and the community ambulation ability, degree of disability and functional mobility of individuals with stroke was studied.

Results

Compared to controls, participants with chronic stroke showed a larger medial-lateral displacement (p = 0.022) in bipedal stance, a higher medial-lateral range (p < 0.001) and a lower cranio-caudal range (p = 0.024) when walking, and lower turn-to-sit power (p = 0.001), turn-to-sit jerk (p = 0.026) and sit-to-stand jerk (p = 0.001) when assessing turn-to-sit-to-stand. Medial-lateral range and total execution time significantly correlated with all the clinical tests (p < 0.005), and resulted significantly different between independent and limited community ambulation patients (p = 0.042 and p = 0.006, respectively) as well as stroke participants with significant disability or slight/moderate disability (p = 0.024 and p = 0.041, respectively).

Conclusion

This study reports a valid, single, quick and easy-to-use test for assessing kinematic parameters in chronic stroke survivors by using a standardized mobility test with a smartphone. This measurement could provide valid clinical information on reaction time and kinematic parameters of postural control and gait, which can help in planning better intervention approaches.
Mechanism of sodium butyrate, a metabolite of gut microbiota, regulating cardiac fibroblast transdifferentiation via the NLRP3/Caspase-1 pyroptosis pathway
Authors: Dong Tiancheng , Huang Dingkao , Jin Zhengzheng
Published: April 2024

Background

Cardiac fibroblasts (CFs) are activated after initial injury, and then differentiate into myofibroblasts (MFs), which play a pivotal role as the primary mediator cells in pathological remodeling. Sodium butyrate (NaB), being a metabolite of gut microbiota, exhibits anti-inflammatory property in local therapies on sites other than the intestine. Thus, this study aimed to probe the mechanism by which NaB regulates CFs transdifferentiation through the NLRP3/Caspase-1 pyroptosis pathway.

Methods

CFs were cultured in vitro and induced into MFs by TGFβ1. CFs were identified by immunofluorescence labelling technique of vimentin and α-SMA, followed by treatment with NaB or NLRP3 inflammasome inhibitor (CY-09) and its activator [nigericin sodium salt (NSS)]. The expression levels of α-SMA, GSDMD-N/NLRP3/cleaved Caspase-1 proteins, and inflammatory factors IL-1β/IL-18/IL-6/IL-10 were determined using immunofluorescence, Western blot and ELISA. Cell proliferation and migration were evaluated using the CCK-8 assay and the cell scratch test, respectively.

Results

Following the induction of TGFβ1, CFs exhibited increased expression levels of α-SMA proteins and IL-6/IL-10, as well as cell proliferative and migratory abilities. TGFβ1 induced CFs to differentiate into MFs, while NaB inhibited this differentiation. NaB inactivated the NLRP3/Caspase-1 pyroptosis pathway. CY-09 demonstrated inhibitory effects on the NLRP3/Caspase-1 pyroptosis pathway, leading to a reduction in TGFβ1-induced CFs transdifferentiation. NSS activated the NLRP3/Caspase-1 pyroptosis pathway, and thus partially counteracting the inhibitory effect of intestinal microbiota metabolite NaB on CFs transdifferentiation.

Conclusion

NaB, a metabolite of the gut microbiota, inhibited the activation of the NLRP3/Caspase-1 pyroptosis pathway in TGFβ1-induced CFs, repressed the transdifferentiation of CFs into MFs.
Torsion of the spiral colon in cattle– a retrospective analysis of 58 cases
Authors: Braun Ueli , Gerspach Christian , Volz Claudia , Hilbe Monika , Nuss Karl
Published: April 2024

Background

Torsion of the spiral colon (TSC) describes twisting of the spiral colon around its mesentery. The present study reviewed the medical records of 58 cows and heifers with TSC and described the findings, treatment and outcome.

Results

All cases had an abnormal general condition, and the main vital sign abnormalities were tachycardia (72.4%), tachypnoea (67.2%) and decreased rectal temperature (51.8%). Signs of colic were seen in 62.1% of the cows. The most common intestinal abnormalities were an empty or almost empty rectum (96.6%), reduced or absent rumen motility (93.2%), positive ballottement and/or percussion and simultaneous auscultation on the right side of the abdomen (87.9%), reduced or absent intestinal motility (84.5%) and dilatation of the large intestines (spiral colon and/or caecum, 70.7%) diagnosed by transrectal palpation. The main biochemical changes were hypermagnesaemia (70.8%), hypocalcaemia (70.8%), and acidosis (66.7%). Haemoconcentration was found in 63.8%. The main ultrasonographic findings were reduced to absent small intestinal motility (83.3%), dilated small intestines (69.6%) and ascites (66.7%). The spiral colon was dilated in 44.0% of the cows and the caecum in 24.0%. The actual site of torsion could not be visualised. Based on the clinical findings, TSC was diagnosed in 22.4% and caecal dilatation in 50.0% of the cows. A tentative diagnosis of small intestinal ileus was made in another 10.3% of the cows, and a definitive diagnosis of small intestinal ileus in 17.3%. Fifty-three cows underwent right flank laparotomy, and the TSC could be reduced in 26. Twenty-six of the 58 (44.8%) cows were discharged and 32 (55.2%) were euthanased before, during or after surgery.

Conclusions

Acute illness, a sparse amount of faeces in the rectum and dilated spiral colon and caecum are characteristic findings of TSC. The final diagnosis often relies on the surgical or postmortem findings. Cattle with TSC should be treated surgically without delay. The prognosis is guarded with a survival rate of 44.8%.
Chitosan modified with PAP as a promising delivery system for melatonin in the treatment of osteoporosis: targeting the divalent metal transporter 1
Authors: Zhang Weilin , Rong Hongrui , Liang Jinguo , Mao Chao , Li Zhencong , Dai Zhiwen , Li Dingbin , Guo Weixiong , Chen Siyuan , Wang Zhongwei , Wei Jinsong
Published: April 2024

The demands for novel and efficient therapies have gradually increased with the rising concerns of osteoporosis (OP). The most popular method in promoting bone regeneration during osteoporotic conditions consists of loading bioactive materials with different drugs to treat osteoporotic bones by either promoting the process of osteogenesis, or by inhibiting the activity of osteoclasts. By analyzing single cell sequencing results, we found that divalent metal transporter 1 (DMT1) played a role in OP. Based on our previous results, we found that melatonin (MT) suppressed expression of DMT1 induced by high glucose during OP, so we determined the efficacy of MT for the treatment of OP. However, the clinical effects of MT on OP were unsatisfactory. To enhance its biological efficacy, we combined MT with porous gelatin chitosan (chitosan) and the conductive material, PLA-b-AP-b-PLA (PAP), then determined how MT incorporation in chitosan@PAP nanoparticles affected the ability to promote MC3T3-E1 osteogenesis and mineralization, both in vitro and in vivo. The results confirmed the effect of MT on DMT1. We then prepared and characterized composites prepared as nanofibers, and determined the efficacy of MT combined with chitosan-PAP modified hydrogels as a slow-release system in a femur model of osteoporosis mice, with associated properties suitable for bone tissue engineering. The results indicated that MT-loaded chitosan@PAP nanospheres showed favorable osteogenic functions, both in vivo and in vitro, providing a practical solution for bone regeneration for OP patients.
Demuxafy: improvement in droplet assignment by integrating multiple single-cell demultiplexing and doublet detection methods
Authors: Neavin Drew , Senabouth Anne , Arora Himanshi , Lee Jimmy Tsz Hang , Ripoll-Cladellas Aida ,   sc-eQTLGen Consortium, Franke Lude , Prabhakar Shyam , Ye Chun Jimmie , McCarthy Davis J. , Melé Marta , Hemberg Martin , Powell Joseph E.
Published: April 2024

Recent innovations in single-cell RNA-sequencing (scRNA-seq) provide the technology to investigate biological questions at cellular resolution. Pooling cells from multiple individuals has become a common strategy, and droplets can subsequently be assigned to a specific individual by leveraging their inherent genetic differences. An implicit challenge with scRNA-seq is the occurrence of doublets—droplets containing two or more cells. We develop Demuxafy, a framework to enhance donor assignment and doublet removal through the consensus intersection of multiple demultiplexing and doublet detecting methods. Demuxafy significantly improves droplet assignment by separating singlets from doublets and classifying the correct individual.
Educational nutritional intervention to prevent loss of health-related quality of life among older adults after a surgical treatment: design of a randomised controlled trial
Authors: Hansen Monica Christin , Uhrenfeldt Lisbeth , Ingstad Kari , Pedersen Preben U.
Published: April 2024

Background

Disease-related malnutrition after a hospital stay has major consequences for older adults, the healthcare system and society. This study aims to develop and test the effectiveness of an educational video to prevent loss of health-related quality of life among live-at-home older adults after surgical treatment in a hospital.

Method

This randomised controlled trial will occur at a regional hospital in Norway. Participants will be live-at-home adults aged 65 years and older. They will be recruited from three different surgical departments after a surgical procedure. Individuals with a body mass index below 24 and a home address in one of nine selected municipalities will be eligible for inclusion. Participants will be randomly assigned to either the intervention group or the control group. Those assigned to the intervention group will obtain access to a 6-min educational video 5 days after being discharged from the hospital. The control group will not obtain access to the video. The primary outcome will be health-related quality of life using the Norwegian Rand 36-Item Short Form Health Survey. Furthermore, we will measure body composition, number of readmissions and nutritional knowledge at inclusion and 3-month follow-up.

Discussion

This randomised controlled trial is expected to provide insight into whether an educational video can improve the nutritional status of older adults following a surgical procedure and discharge from the hospital. The findings will be useful for assessing how videos offering nutritional advice to older adults who have undergone a surgical procedure can improve their health-related quality of life, reduce loss of function, prevent readmission to hospital and reduce healthcare costs.

Trial registration

ClinicalTrials.gov NCT05950373. Registered on 11 July 2023.
Impaired cerebral autoregulation detected in early prevasospasm period is associated with unfavorable outcome after spontaneous subarachnoid hemorrhage: an observational prospective pilot study
Authors: Chaleckas Edvinas , Putnynaite Vilma , Lapinskiene Indre , Preiksaitis Aidanas , Serpytis Mindaugas , Rocka Saulius , Bartusis Laimonas , Petkus Vytautas , Ragauskas Arminas
Published: April 2024

Background

Subarachnoid hemorrhage (SAH) patients with cerebral autoregulation (CA) impairment at an early post-SAH period are at high risk of unfavorable outcomes due to delayed cerebral ischemia (DCI) or other complications. Limited evidence exists for an association between early-stage CA impairments and SAH patient outcomes. The objective of this prospective study was to explore associations between CA impairments detected in early post-SAH snapshot examinations and patient outcomes.

Methods

The pilot observational study included 29 SAH patients whose CA status was estimated 2–3 days after spontaneous aneurysm rupture and a control group of 15 healthy volunteers for comparison. Inflatable leg recovery boots (reboots.com, Germany) were used for the safe controlled generation of arterial blood pressure (ABP) changes necessary for reliable CA examination. At least 5 inflation‒deflation cycles of leg recovery boots with a 2–3 min period were used during examinations. CA status was assessed according to the delay time (∆TCBFV) measured between ABP(t) and cerebral blood flow velocity (CBFV(t)) signals during artificially induced ABP changes at boot deflation cycle. CBFV was measured in middle cerebral artery by using transcranial Doppler device.

Results

Statistically significant differences in ∆TCBFV were found between SAH patients with unfavorable outcomes (∆TCBFV = 1.37 ± 1.23 s) and those with favorable outcomes (∆TCBFV = 2.86 ± 0.99 s) (p < 0.001). Early assessment of baroreflex sensitivity (BRS) during the deflation cycle showed statistically significant differences between the DCI and non-DCI patient groups (p = 0.039).

Conclusions

A relatively small delay of ∆TCBFV <1.6 s between CBFV(t) and ABP(t) waves could be an early warning sign associated with unfavorable outcomes in SAH patients. The BRS during boot deflation can be used as a biomarker for the prediction of DCI.

Trial registration

ClinicalTrials.gov Identifier: NCT06028906. Registered 31 August 2023 - Retrospectively registered, https://www.clinicaltrials.gov/study/NCT06028906.
Supporting athletes during a challenging situation: recommendations from a global insight of COVID-19 home-based training experience
Authors: Washif Jad Adrian , Hettinga Florentina J. , Ammar Achraf , van Rensburg Dina Christa Janse , Materne Olivier , Trabelsi Khaled , Romdhani Mohamed , Farooq Abdulaziz , Pyne David B. , Chamari Karim
Published: April 2024

Background

For athletes, overcoming obstacles in challenging situations like pandemic home training is crucial. Strategies and approaches in this context are not well-documented. Our study aims to investigate such a scenario from a performance standpoint, based on a major global crisis: the COVID-19 pandemic and lockdown.

Methods

This cross-sectional study surveyed athletes without disabilities using online questionnaires (35 languages) from May to July 2020. Questions included aspects of alternative routines, training monitoring, recovery, sleep patterns, injury occurrence/prevention based on structured answers, and an open-ended question on lockdown training experiences.

Results

Of the 11,762 athletes from 142 countries, 63% were male, including at World-Class, International, National, State and Recreational levels. During lockdown, 25% athletes used innovative or modern ways to maintain or improve fitness e.g., virtual reality and tracking devices (favoring World-Class level, 30%). Many athletes, regardless of gender (43%) watched video competitions to improve/maintain their mental skills and performance [World-Class (47%) and International (51%)]. Contact frequency between athletes and their coaches was mainly at least once a week (36%), more among higher-level (World-Class/International) than lower-level athletes (27 vs. 16%). Higher-level athletes (≥ 54%) monitored training load and were assisted by their coaches (21%). During lockdown, stretching (67%) was considered one of the primary means of recovery, especially for higher-level athletes (> 70%). Compared to pre-lockdown, about two-thirds of athletes reported “normal” or “improved” sleep quality and quantity, suggesting a low sleep quality pre-lockdown. On average, 40% utilized injury prevention exercises (at least) once a week [World-Class (51%) and International (39%)]. Most injury occurrences during lockdown involved the knee (18%), ankle (16%), and back (9%). Four key themes emerged regarding lockdown experiences: remote training adaptation (e.g., shifting training focus), training creativity (e.g., using household items), performance enhancement opportunities (e.g., refocusing neglected aspects), and mental and motivation challenges.

Conclusions

Both male and female athletes, particularly those of higher levels, displayed some adaptalibity during the COVID-19 lockdown, employing innovative approaches and technology for training. Many athletes implemented load monitoring, recovery, and attentive of injury prevention, while optimizing their sleep quality and quantity. Athletes demonstrated their abilities to navigate challenges, and utilized different coping strategies in response to the lockdown’s constraints.
DNMT1/miR-152-3p/SOS1 signaling axis promotes self-renewal and tumor growth of cancer stem-like cells derived from non-small cell lung cancer
Authors: Yuan Qing , Wang Rubo , Li Xiang , Sun Fei , Lin Jiazhi , Fu Zhimin , Zhang Jiansong
Published: April 2024

Background

CSLCs(Cancer stem cell-like cells), which are central to tumorigenesis, are intrinsically influenced by epigenetic modifications. This study aimed to elucidate the underlying mechanism involving the DNMT1/miR-152-3p/SOS1 axis in regulating the self-renewal and tumor growth of LCSLCs (lung cancer stem-like cells).

Materials and methods

Target genes of miR-152-3p were predicted using TargetScan Human 8.0. Self-renewal and tumor growth of LCSLC were compared in suspension-cultured non-small cell lung cancer (NSCLC) cell lines H460 and A549 cell-derived globe cells. Functional effects of the DNMT1/miR-152-3p/SOS1 axis were assessed through gain-of-function experiments in vitro and in vivo. Additionally, luciferase reporter assays were employed to analyze the interaction among DNMT1, miR-152-3p, and SOS1.

Results

Our findings highlight a negative interaction between DNMT1 and miR-152-3p, resulting in reduced miR-152-3p level. This, in turn, leads to the alleviation of the inhibitory effect of miR-152-3p on the target gene SOS1, ultimately activating SOS1 and playing an essential role in self-renewal and tumor growth of LCSLC. However, the alteration of SOS1 does not affect DNMT1/miR-152-3p regulation. Therefore, it is reasonable to infer that the DNMT1/miR-152-3p negative feedback loop critically sustains self-renewal and tumor growth of LCSLC through SOS1.

Conclusions

This study reveals a novel mechanism underpinning self-renewal and tumor growth of CSLC (cancer stem cell) in NSCLC and identifies potential therapeutic targets for NSCLC treatment.
STING-dependent trained immunity contributes to host defense against Clostridium perfringens infection via mTOR signaling
Authors: Liu Zhen-Zhen , Zhou Cheng-Kai , Lin Xiao-Qi , Gao Yu , Luo Xue-Yue , Zhang Jia-Bao , Yin Qi , Zhang Liang , Zhang Jian-Gang , An Xin , Chen Wei , Yang Yong-Jun
Published: April 2024

Clostridium perfringens (C. perfringens) infection is recognized as one of the most challenging issues threatening food safety and perplexing agricultural development. To date, the molecular mechanisms of the interactions between C. perfringens and the host remain poorly understood. Here, we show that stimulator of interferon genes (STING)-dependent trained immunity protected against C. perfringens infection through mTOR signaling. Heat-killed Candida albicans (HKCA) training elicited elevated TNF-α and IL-6 production after LPS restimulation in mouse peritoneal macrophages (PM). Although HKCA-trained PM produced decreased levels of TNF-α and IL-6, the importance of trained immunity was demonstrated by the fact that HKCA training resulted in enhanced bacterial phagocytic ability and clearance in vivo and in vitro during C. perfringens infection. Interestingly, HKCA training resulted in the activation of STING signaling. We further demonstrate that STING agonist DMXAA is a strong inducer of trained immunity and conferred host resistance to C. perfringens infection in PM. Importantly, corresponding to higher bacterial burden, reduction in cytokine secretion, phagocytosis, and bacterial killing were shown in the absence of STING after HKCA training. Meanwhile, the high expression levels of AKT/mTOR/HIF1α were indeed accompanied by an activated STING signaling under HKCA or DMXAA training. Moreover, inhibiting mTOR signaling with rapamycin dampened the trained response to LPS and C. perfringens challenge in wild-type (WT) PM after HKCA training. Furthermore, STING‑deficient PM presented decreased levels of mTOR signaling-related proteins. Altogether, these results support STING involvement in trained immunity which protects against C. perfringens infection via mTOR signaling.
Genome analysis of Streptococcus spp. isolates from animals in pre-antibiotic era with respect to antibiotic susceptibility and virulence gene profiles
Authors: Hyeon Ji-Yeon , Kim Junwon , Chung David H. , Helal Zeinab H. , Polkowski Robert , Lee Dong-Hun , Risatti Guillermo R.
Published: April 2024

Lyophilized Streptococcus spp. isolates (n = 50) from animal samples submitted to the diagnostic laboratory at the University of Connecticut in the 1940s were revivified to investigate the genetic characteristics using whole-genome sequencing (WGS). The Streptococcus spp. isolates were identified as follows; S. agalactiae (n = 14), S. dysgalactiae subsp. dysgalactiae (n = 10), S. dysgalactiae subsp. equisimils (n = 5), S. uberis (n = 8), S. pyogenes (n = 7), S. equi subsp. zooepidemicus (n = 4), S. oralis (n = 1), and S. pseudoporcinus (n = 1). We identified sequence types (ST) of S. agalactiae, S. dysgalactiae, S. uberis, S. pyogenes, and S. equi subsp. zooepidemicus and reported ten novel sequence types of those species. WGS analysis revealed that none of Streptococcus spp. carried antibiotic resistance genes. However, tetracycline resistance was observed in four out of 15 S. dysgalactiae isolates and in one out of four S. equi subsp. zooepidemicus isolate. This data highlights that antimicrobial resistance is pre-existed in nature before the use of antibiotics. The draft genome sequences of isolates from this study and 426 complete genome sequences of Streptococcus spp. downloaded from BV-BRC and NCBI GenBank database were analyzed for virulence gene profiles and phylogenetic relationships. Different Streptococcus species demonstrated distinct virulence gene profiles, with no time-related variations observed. Phylogenetic analysis revealed high genetic diversity of Streptococcus spp. isolates from the 1940s, and no clear spatio-temporal clustering patterns were observed among Streptococcus spp. analyzed in this study. This study provides an invaluable resource for studying the evolutionary aspects of antibiotic resistance acquisition and virulence in Streptococcus spp.
Following the tug of the audience from complex to simplified hazards maps at Cascade Range volcanoes
Authors: Driedger Carolyn L. , Ramsey David W. , Scott William E. , Faust Lisa M. , Bard Joseph A. , Wold Patti
Published: April 2024

Volcano-hazard maps are broadly recognized as important tools for forecasting and managing volcanic crises and for disseminating spatial information to authorities and people at risk. As scientists, we might presume that hazards maps can be developed at the time and with the methods of our discretion, yet the co-production of maps with stakeholder groups, who have programmatic needs of their own, can sway the timing, usability, and acceptance of map products.

We examine two volcano hazard map-making efforts by staff at the U.S. Geological Survey. During the 1990s and early 2000s scientists developed a series of hazard assessments and maps with detailed zonations for volcanoes in Washington and Oregon. In 2009, the National Park Service expressed the need for simplified versions of the existing hazard maps for a high-profile visitor center exhibit. This request created an opportunity for scientists to rethink the objectives, scope, content, and map representations of hazards. The primary focus of this article is a discussion of processes used by scientists to distill the most critical information within the official parent maps into a series of simplified maps using criteria specified. We contextualize this project with information about development of the parent maps, public response to the simplified hazard maps, the value of user engagement in mapmaking, and with reference to the abundance of guidance available to the next generation of hazard-mapmakers.

We argue that simplified versions of maps should be developed in tandem with any hazard maps that contain technical complexities, not as a replacement, but as a mechanism to broaden awareness of hazards. We found that when scientists endeavor to design vivid and easy-to-understand maps, people in many professions find uses for them within their organization’s information products, resulting in extensive distribution.
Effects of ankle–foot orthoses on gait parameters in post-stroke patients with different Brunnstrom stages of the lower limb: a single-center crossover trial
Authors: Wu Fangchao , Meng Zhe , Yang Kezhen , Li Jianhua
Published: April 2024

Background

Ankle-foot orthoses (AFO) can improve gait posture and walking ability in post-stroke patients. However, the effect of AFO on gait parameters in post-stroke patients according to the Brunnstrom stage of stroke recovery of the lower limbs remains unclear. The study aimed to investigate whether stroke patients with different Brunnstrom stages benefit from wearing AFO.

Methods

Twenty-five post-stroke participants included 18 men (50 ± 13 years) and 7 women (60 ± 15 years). The patients were divided based on Brunnstrom stage III or IV of the lower limbs. All patients underwent the gait and timed up and go (TUG) test using a gait analysis system while walking barefoot or with an AFO. The spatiotemporal and asymmetric parameters were analyzed.

Results

All 25 patients completed the study. Significant differences were observed between barefoot and AFO use in TUG time (P < 0.001) but not walking velocity (P > 0.05). The main effect of the swing time ratio was significant in both groups (P < 0.05); however, the main effects of stride length, stance time, and gait asymmetry ratio were nonsignificant (P > 0.05). For barefoot versus AFO, the main effects of stride length (P < 0.05) and swing time (P < 0.01) ratios were significant, whereas those of stance time and gait asymmetry ratio were nonsignificant (P > 0.05).

Conclusions

Post-stroke patients with lower Brunnstrom stages benefitted more from AFO, particularly in gait asymmetry.
Development of single-pin, un-barbed, pole-tagging of free-swimming dolphins and sharks with satellite-linked transmitters
Authors: Moore Michael J. , Lanagan Thomas M. , Wells Randall S. , Kapit Jason , Barleycorn Aaron A. , Allen Jason B. , Baird Robin W. , Braun Camrin D. , Skomal Gregory B. , Thorrold Simon R.
Published: April 2024

Background

To tag large marine vertebrates, without the need to catch them, avoiding using barbs for tag retention, and precisely controlling tag location, the remote Tag Attachment Device on a pole (TADpole) was developed. This allows single-pin tags (Finmount, Wildlife Computers) to be attached to the dorsal fins of free-swimming large marine vertebrates.

Results

TADpole comprises a pole-mounted holster that carries a tag. It uses compressed air, and a micro-controller, to rapidly insert a stainless-steel pin through a corrodible metal retaining ring in the first tag attachment wing, the animal’s dorsal fin, and then a press fit Delrin retaining ring in the tag wing on the other side of the fin. Tagging only occurs when the trailing edge of the dorsal fin touches a trigger bar in the holster, ensuring optimal pin placement. It was developed using fins from cadavers, then trialed on briefly restrained coastal dolphins that could be followed in successive days and weeks, and then on free-swimming animals in the field. The latter showed very short touch/response intervals and highlighted the need for several iterative revisions of the pneumatic system. This resulted in reducing the total time from triggering to tag application to ~ 20 ms. Subsequent efforts expanded the TADpole’s applicability to sharks. One free-swimming Atlantic spotted dolphin, two white sharks, and one whale shark were then tagged using the TADpole.

Conclusions

Being able to tag free-swimming dolphins and sharks remotely and precisely with satellite-linked telemetry devices may contribute to solving conservation challenges. Sharks were easier to tag than dolphins. Dolphin touch-to-response times were 28 ms or less. Delphinid skin has unique polymodal axon bundles that project into the epidermis, perhaps a factor in their uniquely fast response, which is 10 × faster than humans. Their primary reaction to tagging is to abduct the flippers and roll the fin out of the TADpole holster. This device has the potential to deliver high-quality tag data from large vertebrates with dorsal fins without the stress and logistics associated with catch-and-release, and without the trauma of tags that use barbs for retention. It also collects a dorsal fin biopsy core.
Controlling structure and interfacial interaction of monolayer TaSe2 on bilayer graphene
Authors: Lee Hyobeom , Im Hayoon , Choi Byoung Ki , Park Kyoungree , Chen Yi , Ruan Wei , Zhong Yong , Lee Ji-Eun , Ryu Hyejin , Crommie Michael F. , Shen Zhi-Xun , Hwang Choongyu , Mo Sung-Kwan , Hwang Jinwoong
Published: April 2024

Tunability of interfacial effects between two-dimensional (2D) crystals is crucial not only for understanding the intrinsic properties of each system, but also for designing electronic devices based on ultra-thin heterostructures. A prerequisite of such heterostructure engineering is the availability of 2D crystals with different degrees of interfacial interactions. In this work, we report a controlled epitaxial growth of monolayer TaSe2 with different structural phases, 1H and 1 T, on a bilayer graphene (BLG) substrate using molecular beam epitaxy, and its impact on the electronic properties of the heterostructures using angle-resolved photoemission spectroscopy. 1H-TaSe2 exhibits significant charge transfer and band hybridization at the interface, whereas 1 T-TaSe2 shows weak interactions with the substrate. The distinct interfacial interactions are attributed to the dual effects from the differences of the work functions as well as the relative interlayer distance between TaSe2 films and BLG substrate. The method demonstrated here provides a viable route towards interface engineering in a variety of transition-metal dichalcogenides that can be applied to future nano-devices with designed electronic properties.
Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis
Authors: Jia Kai-Wei , Yao Ren-Qi , Fan Yi-Wen , Zhang Ding-Ji , Zhou Ye , Wang Min-Jun , Zhang Li-Yuan , Dong Yue , Li Zhi-Xuan , Wang Su-Yuan , Wang Mu , Li Yun-Hui , Zhang Lu-Xin , Lei Ting , Gui Liang-Chen , Lu Shan , Yang Ying-Yun , Wang Si-Xian , Yu Yi-Zhi , Yao Yong-Ming , Hou Jin
Published: April 2024

Background

Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family.

Methods

The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep−/−. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS).

Results

Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis.

Conclusions

This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.
Association between dietary total antioxidant capacity and the risk of stroke: a nested case-control study
Authors: Habibzadeh Adrina , Rahimlou Mehran , Ravankhah Mahdi , Vahid Farhad , Tabrizi Reza
Published: April 2024

Background

Oxidative stress after ischemic stroke contribute to neuronal cell injury. Unhealthy and unbalanced dietary patterns can increase the risk of several diseases, including stroke and cardiometabolic ones. However, the association between dietary total antioxidant capacity (DTAC) of antioxidant and stroke is controversial. Our study aimed to establish a correlation between DTAC and its impact on the occurrence of stroke.

Methods

This nested case–control study included 79 stroke cases and 158 healthy controls. We used data from the Fasa Adults Cohort Study (FACS) comprising 10,035 individuals at baseline. To assess the nutritional status of each individual, a 125-item food frequency questionnaire (FFQ) has been used to evaluate their dietary habits and intakes over the past year. DTAC was calculated using the ferric-reducing antioxidant power (FRAP) international databases. The stroke was confirmed by an experienced neurologist using standard imaging methods. Conditional logistic regression analyses were performed to evaluate the association between DTAC and stroke.

Results

The assessment of DTAC revealed that there was no statistically significant distinction between cases (mean ± SD: 5.31 ± 2.65) and controls (5.16 ± 2.80) with a p-value of 0.95. Even after adjusting for the potentially important confounding factors such as age, sex, event time, energy intake, smoking, hypertension, and diabetes, the association remains non-significant (adjusted odds ratio (OR) = 1.06, 95% CI: 0.94, 1.20, p-value = 0.33).

Conclusions

Our results did not confirm a significant link between DTAC and stroke risk. These findings emphasize the intricate interplay of factors influencing stroke risk and highlight the need for further research to unravel these relationships more comprehensively.
Sodium bicarbonate and intubation in severe diabetic ketoacidosis: are we too quick to dismiss them?
Authors: Vidanapathirana Manudi
Published: April 2024

Management of diabetic ketoacidosis (DKA) has internationally established guidelines. However, management of severe, refractory DKA with multiple contributors to acidosis, and management of DKA in patients with altered mentation, remain ambiguous. Use of sodium bicarbonate and intubation in DKA are unpopular treatment practices, but warrant consideration in these unique clinical scenarios. This paper describes a 61-year-old Sri Lankan female who presented with severe DKA, seizures and altered level of consciousness. In her case, the acidosis was secondary to DKA, hyperlactatemia, hyperchloraemic acidosis and acute kidney injury (AKI). Intravenous sodium bicarbonate was used in the management of acidosis. She was intubated due to altered level of consciousness with inadequate respiratory drive to compensate for metabolic acidosis. The outcome in her case was favorable. Intravenous sodium bicarbonate in DKA should be considered for patients with severe, refractory acidosis with hemodynamic instability, hyperkalemia and compounding acidosis due to normal anion gap acidosis or AKI. Intubation should be considered for patients with obtunded mentation unable to achieve respiratory compensation and obtunded mentation where reversal of DKA is unlikely to improve consciousness. Both strategies should be personalized with consideration of individual risk vs benefit.
Right ventricle involvement in patients with breast cancer treated with chemotherapy
Authors: Rossetto Ludovico , Di Lisi Daniela , Madaudo Cristina , Sinagra Francesco Paolo , Di Palermo Antonio , Triolo Oreste Fabio , Gambino Grazia , Ortello Antonella , Galassi Alfredo Ruggero , Novo Giuseppina
Published: April 2024

Background

Anthracyclines can cause left ventricular (LV) dysfunction. There is little data about right ventricular (RV) damage during chemotherapy.

Aim

This study aimed to investigate the toxic effects of chemotherapy, analyzing its impact on right ventricular function.

Material and Methods

A prospective study was conducted, enrolling 83 female patients (55 ± 11 years old) affected by breast cancer treated with anthracyclines. Cardiological evaluation, HFA risk score assessment and comprehensive echocardiogram, including speckle tracking analysis and 3D analysis, were performed before starting chemotherapy (T0) and at 3 (T1), 6 (T2) and 12 months (T3) after beginning treatment. RV function was assessed with tricuspid annular plane excursion (TAPSE), S’ wave of the tricuspid annulus, fractional area change (FAC), RV global longitudinal strain (RV-GLS), free wall strain (RV-FWLS) and RV 3D ejection fraction (RV-3DEF). Subclinical LV CTRCD was defined as a reduction of GLS > 15% compared to baseline. Subclinical RV cardiotoxicity was defined as the co-presence of a relative decrease of 10% from baseline in RV-3DEF and a relative reduction of 15% from baseline RV-FWLS.

Results

After chemotherapy, we found a significant reduction in 2D-LVEF (p =  < 0.001) and 3D-LVEF (p =  < 0.001), in LV-GLS and RVLS (p =  < 0.001), in FAC and TAPSE, also RV-3DEF reduced significantly (p = 0.002). 39% of patients developed LV subclinical CTRCD; 28% of patients developed RV subclinical cardiotoxicity. LV and RV changes occurred concomitantly, and no RV echocardiographic parameters were found to predict the development of LV CTRCD and vice-versa.

Conclusion

After anthracyclines-based chemotherapy, LV and RV subclinical damage occurs, and it can be detected early by speckle-tracking and 3D echocardiography.
Production of [211At]NaAt solution under GMP compliance for investigator-initiated clinical trial
Authors: Naka Sadahiro , Ooe Kazuhiro , Shirakami Yoshifumi , Kurimoto Kenta , Sakai Toshihiro , Takahashi Kazuhiro , Toyoshima Atsushi , Wang Yang , Haba Hiromitsu , Kato Hiroki , Tomiyama Noriyuki , Watabe Tadashi
Published: April 2024

Background

The alpha emitter astatine-211 (211At) is garnering attention as a novel targeted alpha therapy for patients with refractory thyroid cancer resistant to conventional therapy using beta emitter radioiodine (131I). Herein, we aimed to establish a robust method for the manufacturing and quality control of [211At]NaAt solution for intravenous administration under the good manufacturing practice guidelines for investigational products to conduct an investigator-initiated clinical trial.

Results

211At was separated and purified via dry distillation using irradiated Bi plates containing 211At obtained by the nuclear reaction of 209Bi(4He, 2n)211At. After purification, the 211At trapped in the cold trap was collected in a reaction vessel using 15 mL recovery solution (1% ascorbic acid and 2.3% sodium hydrogen carbonate). After stirring the 211At solution for 1 h inside a closed system, the reaction solution was passed through a sterile 0.22 μm filter placed in a Grade A controlled area and collected in a product vial to prepare the [211At]NaAt solution. According to the 3-lot tests, decay collected radioactivity and radiochemical yield of [211At]NaAt were 78.8 ± 6.0 MBq and 40 ± 3%, respectively. The radiochemical purity of [211At]At− obtained via ion-pair chromatography at the end of synthesis (EOS) was 97 ± 1%, and remained > 96% 6 h after EOS; it was detected at a retention time (RT) 3.2–3.3 min + RT of I−. LC-MS analysis indicated that this principal peak corresponded with an astatide ion (m/z = 210.988046). In gamma-ray spectrometry, the 211At-related peaks were identified (X-ray: 76.9, 79.3, 89.3, 89.8, and 92.3 keV; γ-ray: 569.7 and 687.0 keV), whereas the peak at 245.31 keV derived from 210At was not detected during the 22 h continuous measurement. The target material, Bi, was below the 9 ng/mL detection limit in all lots of the finished product. The pH of the [211At]NaAt solution was 7.9–8.6; the concentration of ascorbic acid was 9–10 mg/mL. Other quality control tests, including endotoxin and sterility tests, confirmed that the [211At]NaAt solution met all quality standards.

Conclusions

We successfully established a stable method of [211At]NaAt solution that can be administered to humans intravenously as an investigational product.
The development and internal validation of a multivariable model predicting 6-month mortality for people with opioid use disorder presenting to community drug services in England: a protocol
Authors: Roberts Emmert , Strang John , Horgan Patrick , Eastwood Brian
Published: April 2024

Background

People with opioid use disorder have substantially higher standardised mortality rates compared to the general population; however, lack of clear individual prognostic information presents challenges to prioritise or target interventions within drug treatment services. Previous prognostic models have been developed to estimate the risk of developing opioid use disorder and opioid-related overdose in people routinely prescribed opioids but, to our knowledge, none have been developed to estimate mortality risk in people accessing drug services with opioid use disorder. Initial presentation to drug services is a pragmatic time to evaluate mortality risk given the contemporaneous routine collection of prognostic indicators and as a decision point for appropriate service prioritisation and targeted intervention delivery. This study aims to develop and internally validate a model to estimate 6-month mortality risk for people with opioid use disorder from prognostic indicators recorded at initial assessment in drug services in England.

Methods

An English national dataset containing records from individuals presenting to drug services between 1 April 2013 and 1 April 2023 (n > 800,000) (the National Drug Treatment Monitoring System (NDTMS)) linked to their lifetime hospitalisation and death records (Hospital Episode Statistics-Office of National Statistics (HES-ONS)). Twelve candidate prognostic indicator variables were identified based on literature review of demographic and clinical features associated with increased mortality for people in treatment for opioid use disorder. Variables will be extracted at initial presentation to drug services with mortality measured at 6 months. Two multivariable Cox regression models will be developed one for 6-month all-cause mortality and one for 6-month drug-related mortality using backward elimination with a fractional polynomial approach for continuous variables. Internal validation will be undertaken using bootstrapping methods. Discrimination of both models will be reported using Harrel’s c and d-statistics. Calibration curves and slopes will be presented comparing expected and observed event rates.

Discussion

The models developed and internally validated in this study aim to improve clinical assessment of mortality risk for people with opioid use disorder presenting to drug services in England. External validation in different populations will be required to develop the model into a tool to assist future clinical decision-making.