bluuebunny/crossref_metadata_2025 huggingface dataset:
Atmospheric escape in hot Jupiters under sub-Alfvénic interactions
Authors: Presa Andrés , Driessen Florian A , Vidotto Aline A
Published: October 2024

Hot Jupiters might reside inside the Alfvén surface of their host star wind, where the stellar wind is dominated by magnetic energy. The implications of such a sub-Alfvénic environment for atmospheric escape are not fully understood. Here, we employ 3D radiation-magnetohydrodynamic simulations and Ly-$\alpha$ transit calculations to investigate atmospheric escape properties of magnetized hot Jupiters. By varying the planetary magnetic field strength ($B_\mathrm{p}$) and obliquity, we find that the structure of the outflowing atmosphere transitions from a magnetically unconfined regime, where a tail of material streams from the nightside of the planet, to a magnetically confined regime, where material escapes through the polar regions. Notably, we find an increase in the planet escape rate with $B_\mathrm{p}$ in both regimes, with a local decrease when the planet transitions from the unconfined to the confined regime. Contrary to super-Alfvénic interactions, which predicted two polar outflows from the planet, our sub-Alfvénic models show only one significant polar outflow. In the opposing pole, the planetary field lines connect to the star. Finally, our synthetic Ly-$\alpha$ transits show that both the red-wing and blue-wing absorptions increase with $B_\mathrm{p}$. Furthermore, there is a degeneracy between $B_\mathrm{p}$ and the stellar wind mass-loss rate when considering absorption of individual Ly-$\alpha$ wings. This degeneracy can be broken by considering the ratio between the blue-wing and the red-wing absorptions, as stronger stellar winds result in higher blue-to-red absorption ratios. We show that, by using the absorption ratios, Ly-$\alpha$ transits can probe stellar wind properties and exoplanetary magnetic fields.
3D hydrodynamic simulations of white dwarf–main-sequence star collisions – I. Head-on collisions
Authors: van der Merwe C J T , Mohamed S S , José J , Shara M , Kamiński T
Published: October 2024

Recently inaugurated telescopes, such as the MeerKAT radio telescope and the upcoming Rubin Observatory Legacy Survey of Space and Time, will be able to detect millions of transient events in the night sky. Stellar collisions between white dwarfs (WDs) and main-sequence (MS) stars may be detectable among such transients. Simulations will play a key role in characterizing these events and selecting targets for follow-up. We present 3D smoothed particle hydrodynamics models of dynamical interactions between a $0.6\ {\rm M}_{\odot }$ WD and 0.3, 0.6, and $1.2\ {\rm M}_{\odot }$ MS stars within globular cluster environments. Utilizing a 34-isotope nuclear network, we investigate the energetics, gas morphologies, and mass-loss properties of these collisions for different stellar mass ratios. Our models predict an overabundance of $^{13}$C, $^{15}$N, and $^{17}$O isotopes relative to solar abundances. Moreover, we find that the time-scale of the collisions is too short and maximum temperatures too low for any significant hydrogen burning or triple-alpha reactions to occur. This combined with a negligible production of elements heavier than neon may be key signatures in distinguishing these events from other transient events with similar peak bolometric luminosities ($\sim\!\! 10^{38}\!\!-\!\!10^{41}$ erg s$^{-1}$).
Human selenocysteine synthase, SEPSECS, has evolved to optimize binding of a tRNA-based substrate
Authors: Puppala Anupama K , Sosa Dylan , Castillo Suchkou Jennifer , French Rachel L , Dobosz-Bartoszek Malgorzata , Kiernan Kaitlyn A , Simonović Miljan
Published: October 2024

The evolution of the genetic code to incorporate selenocysteine (Sec) enabled the development of a selenoproteome in all domains of life. O-phosphoseryl-tRNASec selenium transferase (SepSecS) catalyzes the terminal reaction of Sec synthesis on tRNASec in archaea and eukaryotes. Despite harboring four equivalent active sites, human SEPSECS binds no more than two tRNASec molecules. Though, the basis for this asymmetry remains poorly understood. In humans, an acidic, C-terminal, α-helical extension precludes additional tRNA-binding events in two of the enzyme monomers, stabilizing the SEPSECS•tRNASec complex. However, the existence of a helix exclusively in vertebrates raised questions about the evolution of the tRNA-binding mechanism in SEPSECS and the origin of its C-terminal extension. Herein, using a comparative structural and phylogenetic analysis, we show that the tRNA-binding motifs in SEPSECS are poorly conserved across species. Consequently, in contrast to mammalian SEPSECS, the archaeal ortholog cannot bind unacylated tRNASec and requires an aminoacyl group. Moreover, the C-terminal α-helix 16 is a mammalian innovation, and its absence causes aggregation of the SEPSECS•tRNASec complex at low tRNA concentrations. Altogether, we propose SEPSECS evolved a tRNASec binding mechanism as a crucial functional and structural feature, allowing for additional levels of regulation of Sec and selenoprotein synthesis.
PLAbDab-nano: a database of camelid and shark nanobodies from patents and literature
Authors: Gordon Gemma L , Greenshields-Watson Alexander , Agarwal Parth , Wong Ashley , Boyles Fergus , Hummer Alissa , Lujan Hernandez Ana G , Deane Charlotte M
Published: October 2024

Nanobodies are essential proteins of the adaptive immune systems of camelid and shark species, complementing conventional antibodies. Properties such as their relatively small size, solubility and high thermostability make VHH (variable heavy domain of the heavy chain) and VNAR (variable new antigen receptor) modalities a promising therapeutic format and a valuable resource for a wide range of biological applications. The volume of academic literature and patents related to nanobodies has risen significantly over the past decade. Here, we present PLAbDab-nano, a nanobody complement to the Patent and Literature Antibody Database (PLAbDab). PLAbDab-nano is a self-updating, searchable repository containing ∼5000 annotated VHH and VNAR sequences. We describe the methods used to curate the entries in PLAbDab-nano, and highlight how PLAbDab-nano could be used to design diverse libraries, as well as find sequences similar to known patented or therapeutic entries. PLAbDab-nano is freely available as a searchable web server (https://opig.stats.ox.ac.uk/webapps/plabdab-nano/).
Dynamic configuration and data security for bioinformatics cloud services with the Laniakea Dashboard
Authors: Tangaro Marco Antonio , Antonacci Marica , Donvito Giacinto , Foggetti Nadina , Mandreoli Pietro , Colombo Daniele , Pesole Graziano , Zambelli Federico
Published: October 2024

Technological advances in high-throughput technologies improve our ability to explore the molecular mechanisms of life. Computational infrastructures for scientific applications fulfil a critical role in harnessing this potential. However, there is an ongoing need to improve accessibility and implement robust data security technologies to allow the processing of sensitive data, particularly human genetic data. Scientific clouds have emerged as a promising solution to meet these needs. We present three components of the Laniakea software stack, initially developed to support the provision of private on-demand Galaxy instances. These components can be adopted by providers of scientific cloud services built on the INDIGO PaaS layer. The Dashboard translates configuration template files into user-friendly web interfaces, enabling the easy configuration and launch of on-demand applications. The secret management and the encryption components, integrated within the Dashboard, support the secure handling of passphrases and credentials and the deployment of block-level encrypted storage volumes for managing sensitive data in the cloud environment. By adopting these software components, scientific cloud providers can develop convenient, secure and efficient on-demand services for their users.
Updated EANO guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection—Update 1
Authors: van den Bent Martin J , Franceschi Enrico , Touat Mehdi , French Pim J , Idbaih Ahmed , Lombardi Giuseppe , Rudà Roberta , Schweizer Leonille , Capper David , Sanson Marc , Wesseling Pieter , Weller Michael , Eoli Marica , Anghileri Elena , Bielle Franck , Euskirchen Phillipp , Geurts Marjolein , Wen Patrick Y , Preusser Matthias
Published: October 2024

The standard of care for adult patients with gliomas, glioneuronal, and neuronal tumors consists of combinations of surgery, radiotherapy, and chemotherapy. For many systemic cancers, targeted treatments are a major part of the standard treatment; however, the predictive significance of most of the targets for treatment in systemic cancer is less well-established in central nervous system tumors. In 2023 the European Association for NeuroOncology (EANO) Guideline Committee presented evidence-based recommendations for rational testing of molecular targets for targeted treatments. From all targets reviewed, only testing for BRAF V600E mutations was of proven clinical benefit; despite regulatory approvals for tumor agnostic treatment of NTRK gene fusions and high tumor mutational burden (TMB) for patients with adult brain tumors, the evidence of clinical benefit for adult patients was still limited. This guideline has a modular structure, allowing regular updating of individual sections and adding new ones. The present version (Update 1) presents a review of the rationale of testing for PTEN, H3F3A, MTAP, RET and IDH, and presents an update of the text on TMB high and mismatch repair deficiency. It also presents an overview of the therapeutic yield of routine next-generation sequencing for mutations and fusion detection. The Supplemental File II accompanying this version contains an in-depth review of all targets, whereas, in the main manuscript, the final recommendations of the revised and new targets are presented. Updates will be made on a regular basis.
The feasibility of a multi-site, clinic-supported, and tailored neuro-oncology exercise program
Authors: Daun Julia T , Capozzi Lauren C , Dhruva Tana , Roldan Urgoiti Gloria , McDonough Meghan H , McLaughlin Emma , Bansal Mannat , Brett Allan , Easaw Jacob C , McNeely Margaret L , Francis George J , Williamson Tanya , Danyluk Jessica , Ospina Paula A , Lesiuk Christine , de Robles Paula , Leckie Catriona , Culos-Reed S Nicole
Published: October 2024

Background

To address the lack of access to supportive cancer care resources, the purpose of this study was to examine the feasibility of a tailored exercise program for neuro-oncology patients.

Methods

Patients with a primary brain tumor diagnosis, >18 years, and able to consent in English were recruited at 2 tertiary cancer centers in Alberta. Recruitment occurred via the electronic medical record as well as self-referral. A 12-week, tailored exercise intervention with health coaching was delivered in both one-on-one and group-based formats, either in-person or online. Measures of feasibility included tracking referral, enrollment, intervention completion and adherence, measurement completion, fidelity, participant satisfaction, and safety. Participant-reported outcomes and functional fitness were assessed at baseline and 12 weeks. Objective physical activity was tracked via a Garmin activity tracker.

Results

Recruitment occurred between April 2021–December 2022. N = 70 patients enrolled in the study and n = 51 completed the intervention. The referral rate was 31%, the enrollment rate was 66%, and intervention completion and adherence rates were 82.3% and 89.7%. At baseline and 12 weeks, measurement completion rates were 100% and 77.4% for patient-reported outcomes, and 98.4% and 75.8% for functional fitness. The average wear-time for the activity tracker was 72.8%. Fidelity of intervention delivery was 100% for exercise sessions and 87.8% for health coaching. Overall participant satisfaction was 86.5%. No major and 4 minor adverse events occurred.

Conclusions

Delivery of a tailored neuro-oncology exercise program with referral included via the electronic medical record is feasible. Future work is needed to optimize tailored programming as well as to address factors critical for implementation into standard cancer care.

Clinical Trials Registration

NCT04831190 (https://clinicaltrials.gov/ct2/show/NCT04831190).
Association of Race or Ethnicity With Extended-Spectrum Beta-Lactamase Production in Escherichia Coli: A Case Control Study
Authors: Hemenway Alice N , Biagi Mark , Murrey Timothy F , Sun Jiehuan , Osei-Badu Erica , Salazar-McKinney Adriana , Sanabria Ricardo , Al Zoubi Moamen
Published: October 2024

Background

There are limited and conflicting data regarding the impact of race or ethnicity on the rate of gram-negative antimicrobial resistance. This study was performed to determine whether there is a difference in extended-spectrum beta-lactamase (ESBL) Escherichia coli infection or colonization in minoritized patients when compared to White patients from a diverse US Midwestern city.

Methods

A case control study was performed, with controls with non-ESBL E. coli matched 1:1 to patients with ESBL-producing E coli based on age, sex, and ZIP code. A variety of other evidence-based factors for ESBL Enterobacterales infection and colonization were collected via chart review. Multivariate conditional logistic regression assessed the odds of minoritized patients as compared to White patients, while controlling for other common risk factors for ESBL Enterobacterales.

Results

A total of 364 matched pairs were included in the analysis. Females were the majority of the sample (91%), with median age of 65 years. The majority of the sample identified as White (73%), followed by Hispanic (14%) and Black (10%). Urine cultures made up the majority of the cultures in the sample (97%), and this was similar between ESBL and non-ESBL groups. While controlling for these risk factors for ESBL E coli, minoritized patients had a statistically significant greater odds of ESBL-producing E coli (odds ratio, 2.53; 95% confidence interval, 1.68–3.82).

Conclusions

In our sample, which is demographically similar to the United States, minoritized patients had higher odds of ESBL-producing E coli. Further research on the drivers for this disparity is needed.
Impact of the COVID-19 Pandemic on Group A Streptococcal Necrotizing Soft Tissue Infections: A Retrospective Cohort Study
Authors: Epprecht Gioia , Weller David , Hofmaenner Daniel A , Andrianaki Angeliki M , Frey Pascal M , Brugger Silvio D , Zinkernagel Annelies S
Published: October 2024

Background

Necrotizing soft tissue infections (NSTIs) are often caused by group A Streptococcus (GAS). As the number of invasive GAS infections decreased during the coronavirus disease 2019 (COVID-19) pandemic restrictions, this study aimed to compare the occurrence of GAS-NSTIs before, during, and after the COVID-19 pandemic restrictions.

Methods

This retrospective cohort study included adult patients with NSTIs admitted to the intensive care unit (ICU) of the University Hospital Zurich, Switzerland, from July 2008 to December 2023. NSTI cases were categorized as pre-, during, and postrestrictions. The primary outcome was the proportion of GAS in NSTI, and the exploratory secondary outcome was in-hospital death. A data analysis was conducted using Firth logistic regression adjusted for age, sex, diabetes, and initially affected body region.

Results

Overall, 74 NSTI cases were identified, with 49 occurring before, 8 during, and 17 after the pandemic restrictions. GAS was isolated in 27 (36%) cases, with 17 (35%) pre- and 10 (59%) postrestrictions, but none during the restrictions. NSTIs caused by other bacteria persisted during the restrictions. The odds of GAS were significantly lower during the restrictions (adjusted odds ratio, 0.02; 95% CI, 0.001–0.81) compared with after, while no significant differences were found between the pre- and postrestriction periods.

Conclusions

The significant decrease of GAS-NSTIs during the COVID-19 pandemic restrictions suggests that isolation measures may have prevented the transmission of GAS, resulting in a decline of GAS-NSTIs while NSTIs caused by bacteria transmitted by alternative routes persisted.
Effects of Pitavastatin on COVID-19 Incidence and Seriousness Among a Global Cohort of People With HIV
Authors: Zanni Markella V , Umbleja Triin , Fichtenbaum Carl J , Fitch Kathleen V , McCallum Sara , Aberg Judith A , Overton Edgar Turner , Malvestutto Carlos D , Bloomfield Gerald S , Currier Judith S , Schnittman Samuel R , Erlandson Kristine M , Diggs Marissa R , Foldyna Borek , Martinez Esteban , Somboonwit Charurut , Wang Gary P , Mushatt David , Connick Elizabeth , Lu Michael T , Douglas Pamela S , Ribaudo Heather J , Grinspoon Steven K
Published: October 2024

Background

Among people with HIV (PWH), COVID-19 is common and potentially severe. We leveraged REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) to assess the effects of statin therapy for cardiovascular disease prevention on COVID-19 outcomes (incidence and serious cases) among a global cohort of PWH.

Methods

COVID-19 data collection was implemented April 2020 to capture events from January 2020. COVID-19 was defined by positive test result or clinical diagnosis and serious COVID-19 according to the International Conference on Harmonisation definition. Among participants in follow-up on 1 January 2020, Cox proportional hazards modeling was used to estimate the hazard ratio (HR) of COVID-19 (pitavastatin/placebo), stratified by Global Burden of Disease region. Modification of statin effect following COVID-19 vaccination was evaluated via interaction with time-updated vaccination status.

Results

Among 6905 PWH, 32% were natal female and 41% were Black or African American. The median age was 53 years and the 10-year atherosclerotic cardiovascular disease risk score 4.5%. Statin therapy did not reduce COVID-19 incidence (HR, 1.05; 95% CI, .95–1.15) but appeared to reduce incidence of serious COVID-19 (HR, 0.75; 95% CI, .52–1.09). Among 1701 PWH with COVID-19, the relative risk (pitavastatin/placebo) for serious COVID-19 was 0.73 (95% CI, .52–1.03). The treatment effect size for serious COVID-19 fell within the hypothesized range, but the 95% CI crossed 1 given fewer-than-anticipated cases (117 vs 200). Furthermore, 83% reported COVID-19 vaccination by end of study, with a strong protective effect on serious COVID-19 (HR, 0.27; 95% CI, .14–.53; P < .0001). A protective statin effect was observed prior to vaccination.

Conclusions

Among PWH, statin therapy had no effect on COVID-19 incidence but showed potential to reduce risk of serious COVID-19 prior to COVID-19 vaccination.

Clinical Trials Registration

NCT02344290 (ClinicalTrials.gov).
Crohn’s disease presenting with pleural effusion: a case report
Authors: Ahmed Harem K , Hiwa Dilan S , Tahir Soran H , Ali Rawa M , Gharib Dana T , Asaad Hoshmand R , Hamahussein Karokh F , Mohammed Ayoob A , Najar Kayhan A , Kakamad Fahmi H
Published: October 2024

Crohn’s disease (CD) is a granulomatous inflammatory bowel disease. Around 25% of CD patients exhibit extraintestinal manifestations, though pulmonary involvement is rare. This study presents a case of CD causing pleural effusion. A 43-year-old man visited the pulmonology clinic with a dry cough for one-month, right-side pleuritic chest pain, and exertional dyspnea. He was treated with antihistamines and antitussive syrup, with incomplete relief. A chest CT scan showed bilateral mild pleural effusion. Given his occasional black stools and high serum calprotectin, a colonoscopy confirmed CD. Pulmonary manifestations may involve airway, parenchymal, and interstitial pathologies, but no distinctive pathological findings differentiate CD’s pulmonary manifestations from other causes. In conclusion, isolated bilateral pleural effusion and the underlying pleuritis as a pulmonary manifestation of CD—characterized by dry cough and pleuritic chest pain, particularly preceding the diagnosis of CD—is extremely rare but possible.
The dependence of galaxy properties on the underlying three-dimensional matter density field at 2.0 < z < 2.5
Authors: Momose Rieko , Lee Khee-Gan , Ata Metin , Horowitz Benjamin , Kartaltepe Jeyhan S
Published: October 2024

We study the environmental effect of galaxy evolution as a function of the underlying three-dimensional dark matter density for the first time at $z=2$–2.5, in which the underlying matter density is reconstructed from observed galaxies through dynamical forward modeling techniques. Utilizing this map, we investigate the dependence of the star formation activities and galaxy types (mergers, submillimeter galaxies, active galactic nuclei, and quiescent galaxies) on the matter overdensity $\Delta _{\rm local}$ and stellar mass. For the first time, we are able to probe underdense regions ($\Delta _{\rm local}\\lt 1$) in addition to overdensities. We find that star formation activity generally depends on the stellar mass, not the matter density. We also find evidence that there is an absence of mergers and submillimeter galaxies in higher-density regions but otherwise no trend across lower-density bins, and that there is an increase in the prevalence of active galactic nuclei and quiescent galaxies as a function of matter density, and an increase of all aforementioned categories with stellar mass. These results indicate that stellar mass is the main driver of galaxy evolution at the cosmic noon. Our novel approach directly using reconstructed dark matter density maps demonstrates the new capability of studies of the environmental effect of galaxy evolution at higher redshift.
A mixed-methods exploration of the Real-Time Virtual Support pathway Child Health Advice in Real-Time Electronically in Northwestern BC
Authors: Duke Sean , Treissman Jenna , Freeman Shannon , Rossnagel Emma , Somani Salima , Lakhani Alam , Miller Kirsten , Pawlovich John , Wensley David
Published: October 2024

Objectives

To explore the implementation of a provincial virtual paediatric consulting service, Child Health Advice in Real-Time Electronically (CHARLiE), integrated into the paediatric on-call schedule in Northwestern British Columbia.

Methods

Healthcare providers in Northwestern British Columbia responded to a survey (n = 72) and participated in focus groups (n = 35) and key informant interviews (n = 4) to share their experiences engaging in a healthcare model that incorporated virtual paediatric consultants in lieu of in-person local paediatrician coverage over a 28-month period. Survey data was analyzed using descriptive statistics. Themes were generated from a qualitative descriptive approach to focus groups and key informant interview transcripts.

Results

96.1% of survey respondents who had used CHARLiE rated it as ‘good’ or ‘very good’ in the provision of overall support, while 77.6% reported that CHARLiE improved access to paediatric care. Focus group and key informant interview participants valued CHARLiE’s timely, dedicated virtual bedside assessments of patients; collegiality and professionalism; amelioration of local paediatrician burnout; prevention of unnecessary transfers; and offloading of indirect patient care tasks. Video support improved provider confidence and appeared to improve caregiver trust. Suggested improvements included addressing technological barriers, enhancing providers’ knowledge of local resources, and enabling continuity of care. Participants identified that virtual care does not replace on-the-ground specialist care.

Conclusions

Participants valued CHARLiE’s 24/7, timely, and collegial video support. While maintaining a full complement of on-the-ground paediatricians remains the goal for some rural communities, dedicated virtual support provides access to paediatric care in smaller communities, thereby improving health equity for children in British Columbia.
Targeting ESM1 via SOX4 promotes the progression of infantile hemangioma through the PI3K/AKT signaling pathway
Authors: Li Yanan , Kong Meng , Qiu Tong , Ji Yi
Published: October 2024

Background

Infantile hemangioma (IH) is the most prevalent benign vascular tumor in children, yet its pathogenesis remains incompletely understood. Research has established a strong association between SOX4 and tumor blood vessel formation. The objective of this study was to investigate the function and underlying mechanism of SOX4 in IH development with the aim of identifying novel therapeutic targets.

Methods

We identified the transcription factor SOX4 associated with IH through RNA-seq screening of IH microtumors and validated it in IH tissues. The effect of SOX4 on the biological behavior of CD31+ hemangioma-derived endothelial cells (HemECs) was investigated via in vitro cell experiments. In addition, RNA-seq analysis was performed on CD31+ HemECs with low expression levels of SOX4, and the target genes of SOX4 were identified. Finally, the effect of SOX4 on tumor angiogenesis was further elucidated through 3D microtumor and animal experiments.

Results

SOX4 is highly expressed in IH tissues and promotes the proliferation, migration, and angiogenesis of CD31+ HemECs. In addition, SOX4 binds to the endothelial cell-specific molecule 1 (ESM1) promoter to promote the progression of the PI3K/AKT signaling pathway. Finally, through IH 3D microtumor and animal experiments, SOX4 and ESM1 are shown to be tumorigenic genes that independently promote tumor progression.

Conclusions

SOX4 plays a crucial role in the progression of IH, and the SOX4/ESM1 axis may serve as a novel biomarker and potential therapeutic target for IH.
SYNTAXIN OF PLANTS 132 underpins secretion of cargoes associated with salicylic acid signaling and pathogen defense
Authors: Waghmare Sakharam , Xia Lingfeng , Ly Thu Phan , Xu Jing , Farami Sahar , Burchmore Richard , Blatt Michael R , Karnik Rucha
Published: October 2024

Secretory trafficking in plant cells is facilitated by SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins that drive membrane fusion of cargo-containing vesicles. In Arabidopsis, SYNTAXIN OF PLANTS 132 (SYP132) is an evolutionarily ancient SNARE that functions with syntaxins SYP121 and SYP122 at the plasma membrane. Whereas SYP121 and SYP122 mediate overlapping secretory pathways, albeit with differences in their importance in plant–environment interactions, the SNARE SYP132 is absolutely essential for plant development and survival. SYP132 promotes endocytic traffic of the plasma membrane H+-ATPase AHA1 and aquaporin PIP2;1, and it coordinates plant growth and bacterial pathogen immunity through PATHOGENESIS-RELATED1 (PR1) secretion. Yet, little else is known about SYP132 cargoes. Here, we used advanced quantitative tandem mass tagging (TMT)-MS combined with immunoblot assays to track native secreted cargo proteins in the leaf apoplast. We found that SYP132 supports a basal level of secretion in Arabidopsis leaves, and its overexpression influences salicylic acid and jasmonic acid defense-related cargoes including PR1, PR2, and PR5 proteins. Impairing SYP132 function also suppressed defense-related secretory traffic when challenged with the bacterial pathogen Pseudomonas syringae. Thus, we conclude that, in addition to its role in hormone-related H+-ATPase cycling, SYP132 influences basal plant immunity.
Trigger point injections for myofascial pain in terminal cancer: a randomized trial
Authors: Hasuo Hideaki , Ishiki Hiroto , Matsuda Yoshinobu , Matsuoka Hiromichi , Kosugi Kazuhiro , Xing Mei , Akiyama Yasushi , Matsumoto Yoshihisa , Ishikawa Hideki
Published: October 2024

Objective

The aim of this study was to evaluate the efficacy and safety of a single trigger point injection (TPI) of a local anesthetic for the treatment of myofascial pain syndrome (MPS) in patients with incurable cancer.

Methods

This multicenter, exploratory, open-label, randomized comparative trial was conducted in five specialized palliative care departments. Hospitalized patients with incurable cancer who had been experiencing pain related to MPS were randomized to receive either a TPI of 1% lidocaine plus conventional care (TPI group) or conventional care alone (control group). The short-term efficacy and occurrence of adverse events (AEs) were compared between groups. The primary endpoint was the percentage of patients who experienced a reduction in pain scores of ≥50%, assessed using an 11-point Numerical Rating Scale, at 3 days post-intervention. Adverse events were assessed using the Common Terminology Criteria for AEs v5.0.

Results

Fifty patients were enrolled, and the trial completion rate was 100%. The proportion of patients who experienced an improvement in Numerical Rating Scale pain scores of ≥50% was 70.8% (95% confidence interval, 52.4%-89.2%) in the TPI group and 0.0% in the control group; the difference was statistically significant (P < .001). In the TPI group, one case (4.2%) of Grade 1 nausea and 1 case (4.2%) of Grade 1 somnolence were reported.

Conclusion

A single TPI of a local anesthetic is safe and efficacious in inducing an immediate reduction in MPS-related pain in patients with incurable cancer.

Clinical trials registration number: This study was registered with the Japan Registry of Clinical Trials (approval number: jRCTs051210132) on December 16, 2021. https://jrct.niph.go.jp/en-latest-detail/jRCTs051210132.

Approval of the research protocol by a Certified Review Board: The present study was approved by the Wakayama Medical University (reference number: CRB5180004. Registered 26 May 2021).
A complete classification of evolutionary games with environmental feedback
Authors: Ito Hiromu , Yamamichi Masato
Published: October 2024

A tragedy of the commons, in which rational behavior of individuals to maximize their own payoffs depletes common resources, is one of the most important research topics in game theory. To better understand the social dilemma problem, recent studies have developed a theoretical framework of feedback-evolving game where individual behavior affects an environmental (renewable) resource and the environmental resource changes individual payoffs. While previous studies assumed that the frequency of defectors increases (prisoner's dilemma [PD] game) when the environmental resource is abundant to investigate an oscillating tragedy of the commons, it is also possible for other types of game to produce the social dilemma. In this paper, we extend the feedback-evolving game by considering not only PD game, but also the other three game structures when the environmental resource is replete for a reasonably complete classification. The three games are Chicken game where defectors and cooperators coexist through minority advantage, Stag-Hunt (SH) game with minority disadvantage, and Trivial game where the frequency of cooperators increases. In addition, we utilize a dilemma phase plane to visually track (transient) dynamics of game structure changes. We found that an emergent initial condition dependence (i.e. bistability) is pervasive in the feedback-evolving game when the three games are involved. We also showed that persistent oscillation dynamics arise even with Chicken or SH games in replete environments. Our generalized analysis will be an important step to further extend the theoretical framework of feedback-evolving game to various game situations with environmental feedback.
Spatial multiomic insights into acute cocaine exposure
Authors: Nezhyva Mariya , Shahen-Zoabi Samah , Kabirova Marina , Bentov-Arava Einav , Shalev Ori , Andrén Per E , Thornton Claire , Yaka Rami , Margulis Katherine , Jansson Erik T
Published: October 2024

Recent studies provide compelling evidence that cocaine-induced neurotoxicity begins within hours of a single acute cocaine exposure. Despite this, a comprehensive understanding of the molecular alterations occurring in vivo within the reward system following such an exposure has been lacking. In this study, we developed an analytical workflow that combines desorption electrospray ionization mass spectrometry imaging of metabolites at different temperatures with microscale proteomics of brain regions. We present a multiomic perspective on the molecular consequences of acute cocaine exposure on the principal areas of the reward system and the hippocampus. Our findings include distinct region-specific alterations in the tricarboxylic acid cycle and lipid synthesis within the reward circuitry highlighting a significant energy depletion in mice 24 hours post-cocaine injections. Additionally, we linked widespread reductions in key neurotransmitters across the reward system and calcium-level alterations, to changes in synaptic plasticity and mitochondrial dysfunction. Mitochondrial dysfunction and energy metabolism disruption were evident through imbalances in the mitochondrial adenosine triphosphate production and electron transport chain components, increased susceptibility to oxidative stress, disturbances in mitochondrial transport proteins, and fluctuations in creatine and taurine levels. Among the brain regions within the reward circuitry, the prefrontal cortex exhibited the most pronounced effects. This study provides a holistic overview of the intricate interplay between proteins and metabolites, unveiling molecular mechanisms within the reward circuitry regions affected during the onset of cocaine-induced neurotoxicity.
Modeling Upper Limb Rehabilitation-Induced Recovery after Stroke: The Role of Attention as a Clinical Confounder
Authors: Salvalaggio Silvia , Gambazza Simone , Ando’ Martina , Parrotta Ilaria , Burgio Francesca , Danesin Laura , Busan Pierpaolo , Zago Sara , Mantini Dante , D’Imperio Daniela , Zorzi Marco , Filippini Nicola , Turolla Andrea
Published: October 2024

Objective

People who have survived stroke may have motor and cognitive impairments. High dose of motor rehabilitation was found to provide clinically relevant improvement to upper limb (UL) motor function. Besides, mounting evidence suggests that clinical, neural, and neurophysiological features are associated with spontaneous recovery. However, the association between these features and rehabilitation-induced, rather than spontaneous, recovery has never been fully investigated.

The objective was to explore the association between rehabilitation dose and UL motor outcome after stroke, as well as to identify which variables can be considered potential candidate predictors of motor recovery.

Methods

People who survived stroke were assessed before and after a period of rehabilitation using motor, cognitive, neuroanatomical, and neurophysiological measures. We investigated the association between dose of rehabilitation and UL response (ie, Fugl-Meyer Assessment for upper extremity [FMA-UE]), using ordinary least squares regression as the primary analysis. To obtain unbiased estimates, adjusting covariates were selected using a directed acyclic graph.

Results

Baseline FMA-UE was the only factor associated with motor recovery (b = 0.99; 95% CI = 0.83 to 1.15 points). Attention emerged as a confounder of the association between rehabilitation and final FMA-UE (b = 5.5; 95% CI = −0.8 to 11.9 points), influencing both rehabilitation and UL response.

Conclusion

Preserved attention in people who have survived stroke might lead to greater UL motor recovery, albeit estimates have high levels of variability. Moreover, the increase in the dose of rehabilitation can lead to 5.5 points improvement on the FMA-UE, a nonsignificant but potentially meaningful finding. The approach described here discloses a new framework for investigating the effect of rehabilitation treatment as a potential driver of recovery.

Impact

Attentional resources could play a key role in UL motor recovery. There is a potential association between amount of UL recovery and dose of rehabilitation delivered, needing further exploration. Preserved attention and rehabilitation dose are candidate predictors of UL motor recovery.
Saving the breeds: Farmers’ preferences for endangered dairy breed conservation programmes
Authors: Schreiner Julia Anette , Latacz-Lohmann Uwe
Published: October 2024

Concentration on elite breeding lines has endangered a number of traditional dairy breeds. Although several of those breeds are known for superior functional traits such as robustness, they are increasingly replaced by Holstein cows. A discrete choice experiment with 159 breeders revealed the determinants of farmers’ willingness to join a stylized scheme to conserve endangered dairy breeds. Results of a random parameter logit model showed that farmers favour short-term contracts and a bonus for a collective cattle population increase. By contrast, farmers tend to reject schemes that ban slatted floors. The majority of the respondents would be willing to join an entry-level scheme without financial support, pointing to an important role of intrinsic motivation present in farmers, which seems to be particularly pronounced for small breeds threatened by extinction. If it is the political will to offer such conservation schemes, we recommend inclusion of a collective bonus. This finding is also supported by the results of a latent class analysis. A collective bonus might change social norms regarding the conservation of endangered breeds and provide impetus for increasing the overall population of a specific breed.
Association of serum interferon alpha-2a levels with disease severity and prognosis in systemic sclerosis
Authors: Gerges Elias , Cauvet Anne , Schwarz Maximilian , Avouac Jérôme , Allanore Yannick
Published: October 2024

Objective

To determine serum type I IFN (IFN-α2a) concentrations in SSc patients, explore its association with cytokine/chemokine expressions and evaluate correlation with the phenotype including the predictive value for interstitial lung disease (ILD) progression.

Methods

Serum samples were obtained from 200 SSc patients and 29 healthy controls. IFN-α2a levels were measured by ultrasensitive electrochemiluminescence assay. Pro-inflammatory and chemokine panels were determined by Luminex® Discovery Assay multiplex kit. Baseline SSc disease characteristics were recorded together with longitudinal data for determining ILD progression after 2 years.

Results

IFN-α2a concentrations were higher in SSc patients compared with controls, although not reaching significance [means ± SD of 49.20 ± 156.8 pg/ml vs 9.606 ± 4.399 pg/ml, respectively (P = 0.158)]. Using the cut-off of 15.9 pg/ml, we identified 62 patients as having a type 1 (T1) IFN signature in their circulation. Patients with an IFN signature had significantly higher levels of chemokines (CCL8, CCL19, CXCL10, CXCL11) and the cytokine IL-1α compared with those without an IFN signature. IFN-α2a concentrations strongly correlated with a T1 IFN-related chemokine score supporting activation of this pathway. Phenotyping association queries revealed association between IFN values and both skin and ILD involvements at baseline. Longitudinal data did not identify IFN as a predictive marker for ILD progression.

Conclusion

Using serum determinations, the activation of the T1 IFN pathway showed strong correlations with inflammatory mediators and associations with clinical manifestations, especially skin fibrosis and ILD in SSc patients. However, activated IFN pathway was not predictive of ILD progression.
Impact of treatments on fatigue in axial spondyloarthritis: a systematic review and meta-analysis
Authors: Delcourt Clémentine , Fakih Olivier , Prati Clément , Chouk Mickaël , Wendling Daniel , Verhoeven Frank
Published: October 2024

Objectives

Fatigue is frequent in axial SpA (axSpA) and is difficult to improve. This systematic review aimed to assess the effects of axSpA treatment on fatigue.

Methods

A systematic review following the PRISMA recommendations was performed on PubMed, Cochrane and Embase databases. We included controlled interventional studies, cohort studies conducted in patients with axSpA meeting the ASAS 2009 criteria and measuring fatigue between 12 and 156 weeks of treatment. We excluded studies not written in English, case reports, abstracts, systematic reviews, meta-analysis and studies with missing data. A meta-analysis was performed for anti-TNF/anti-IL-17/JAK inhibitors randomized controlled trials evaluating fatigue at week 12–16.

Results

A total of 1672 studies were identified, of which 34 were selected for analysis. Twelve studies evaluated anti-TNF with a significant reduction in fatigue measured by various scores (FACIT, MFI, NRS, VAS, FSS) in 11 studies. Among the four studies evaluating anti-IL-17, three showed a reduction in fatigue, with a dose effect for secukinumab. Two studies evaluated JAK inhibitors and showed a reduction in fatigue. The meta-analysis showed no differences between the DMARDs. Concerning non-pharmacological treatments, 12 of 16 studies showed a reduction in fatigue using physical activity, cryotherapy and magnetotherapy. Two studies showed that the addition of physical activity to anti-TNF reduced fatigue more significantly. Finally, one study showed a greater efficacy in men, and two studies suggested it in non-radiographic form.

Conclusion

This review shows a beneficial effect of DMARD and non-pharmacological treatment on fatigue in axSpA in short and medium terms with a greater effect when combining them.
Donatio mortis causa: new signs of life? Rahman v Hassan [2024] EWHC 1290 (Ch)
Authors: Moppett William
Published: October 2024

In Rahman v Hassan [2024] EWHC 1290 (Ch), HHJ Paul Matthews held that registered land and online bank and shareholding accounts can form the subject-matter of donatio mortis causa, and that, respectively, handing over the land certificate or certain lease documents, and sharing the login/password, can suffice for ‘parting with dominion’ over them. It is suggested that difficulty regarding these assets stems from ambiguity as to whether the function of the ‘sufficient step to implement’/‘parting with dominion’ element(s) of the doctrine is to evidence donative intention or to perform a ‘transitive’ function (and, if the latter, what that function is).
The effect of methionine supplementation on receiving beef steers following a lipopolysaccharide challenge
Authors: Barker Samantha N , Jackson Treylr C , Burdick Sanchez Nicole C , Carroll Jeffery A , Broadway Paul R , Hales Kristin E , Ducharme Gary , Legako Jerrad F , Richeson John T
Published: October 2024

The objective of this study was to evaluate the effects of methionine supplementation prior to and during a lipopolysaccharide (LPS) challenge on the performance and inflammatory biomarkers of receiving beef steers. Steers (n = 65; 295.8 ± 46.5 kg) were randomly assigned to 3 treatment groups: L0 = Control, receiving no supplement; L1 = 10 g/hd/d rumen-protected methionine (MetaSmart, Adisseo USA Inc., Alpharetta, GA); and L2 = 20 g/hd/d rumen-protected methionine and fed for 40 d at the West Texas A&M University Research Feedlot. On day 40, a subset of steers (n = 32; L0 = 10; L1 = 11; L2 = 11) were transported to the USDA Livestock Issues Research Unit, and on day 41 steers were weighed and fitted with indwelling rectal thermometers and jugular catheters. On day 42, steers were challenged i.v. with LPS (0.25 µg/kg BW). Blood samples were collected at −2, 0, 2, 4, 6, 8, 10, 12, 18, 24, 36, and 48 h relative to the LPS administration at 0 h. Serum was isolated to determine serum chemistry and inflammatory marker concentrations. Whole blood was used for hematology analysis. There were no differences in DMI or ADG (P ≥ 0.75) during 35 d of supplementation. A treatment × time interaction (P = 0.01) occurred for rectal temperature, where L2 steers had the greatest temperature following the challenge (P ≤ 0.05) compared to L1 and L0 steers. There was a treatment × time interaction (P = 0.03) for the change in white blood cells where L0 steers had the greatest change compared to L1 and L2 steers at various timepoints. There was a treatment × time interaction (P = 0.02) for the change in tumor necrosis factor-α concentration, where there was a greater increase in concentration in L0 compared to L1 and L2 steers. Additionally, there was a treatment × time interaction (P < 0.01) for Macrophage Inflammatory Protein-1β (MIP-1β) concentrations, where concentrations were greater in L0 compared with L1 and L2 steers from 2 to 4 h post-challenge. There was a treatment × time interaction for plasma total protein concentration (P < 0.01) where L0 steers had less plasma total protein compared with L1 and L2 steers, while L1 steers had less plasma total protein than L2 steers at −2 h prior to LPS challenge. These data suggest that methionine supplementation may have an immunomodulatory effect in beef steers that may improve response to pathogens.
Trophoblast‐specific overexpression of adiponectin receptor 2 causes fetal growth restriction in pregnant mice
Authors: Dumolt Jerad H. , Rosario Fredrick J. , Barentsen Kenneth , Urschitz Johann , Powell Theresa L. , Jansson Thomas
Published: October 2024

Maternal obesity in pregnancy is strongly associated with complications such as fetal overgrowth and infants of obese mothers have an increased risk to develop obesity, diabetes, and cardiovascular disease later in life. However, the underlying mechanisms are not well established. Circulating levels of adiponectin are low in obese pregnant women and maternal circulating adiponectin is negatively associated with birth weight. We have reported that normalizing maternal adiponectin in obese pregnant mice prevents placental dysfunction, fetal overgrowth, and programming of offspring cardio‐metabolic disease. However, the mechanistic link between maternal adiponectin, placental function, and fetal growth remains to be established. We hypothesized that trophoblast‐specific overexpression of the adiponectin receptor 2 (Adipor2) in healthy pregnant mice inhibits placental mTORC1 signaling and nutrient transport, resulting in fetal growth restriction. Using lentiviral transduction of blastocysts with a mammalian gene expression lentiviral vector for up‐regulation of Adipor2 (Adipor2‐OX), we achieved a ~ 3‐fold increase in placenta Adipor2 mRNA levels and a 2‐fold increase of the ADIPOR2 protein in the trophoblast plasma membrane. Placenta‐specific Adipor2‐OX increased placental peroxisome proliferator‐activated receptor‐α phosphorylation, ceramide synthase expression and ceramide concentrations. Furthermore, Adipor2‐OX inhibited placental mTORC1 signaling and reduced in vivo placental transport of glucose and amino acids. Lastly, Adipor2‐OX reduced fetal weight by 11%. These data provide mechanistic evidence that placental Adipor2 signaling directly affects fetal growth. We propose that low circulating adiponectin in maternal obesity causes fetal overgrowth and programs the offspring for cardio‐metabolic disease mediated by a direct effect on placental function.