bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Neck and Jawline Aesthetics With OnabotulinumtoxinA by Minimizing Platysma Muscle Contraction Effects: Efficacy and Safety Results in a Phase 3 Randomized, Placebo-Controlled Study
Authors: Shridharani Sachin M , Ogilvie Patricia , Couvillion Megan , Pavicic Tatjana , Lain Edward , Jierjian Edward , Lee Elisabeth , Park Grace S , Shimoga Sandhya , Tong Warren , Hopfinger René
Published: October 2024

Background

Platysma prominence (PP) describes the noticeable appearance of the platysma muscle upon contraction, causing a less defined jawline contour and vertical neck bands.

Objectives

The objective of this study was to assess the safety and efficacy of onabotulinumtoxinA for improvement of PP in adults.

Methods

Participants with moderate to severe (Grade 3 to 4) PP at maximum contraction received onabotulinumtoxinA or placebo on Day 1 and were monitored for 120 days. OnabotulinumtoxinA dosage (26, 31, or 36 U) was customized based on baseline PP severity on each side of the neck.

Results

Efficacy analyses were conducted in the intent-to-treat (ITT) population (all randomized participants), and modified ITT population (mITT; psychosocially impacted by PP appearance). Results from ITT and mITT populations were comparable. As assessed by investigators, 76.7% of onabotulinumtoxinA mITT participants achieved ≥1-grade improvement vs 21.2% in the placebo group, and 41.0% vs 2.2% (P < .0001) achieved ≥2-grade improvement at Day 14. As assessed by participants, 79.9% of onabotulinumtoxinA mITT participants vs 21.8% in the placebo group and 40.8% vs 3.9% (P < .0001) achieved ≥1- or ≥2-grade improvement, respectively, at Day 14. OnabotulinumtoxinA responder rates remained higher than placebo through Day 120, gradually declining over time. OnabotulinumtoxinA participants reported significantly higher satisfaction with treatment effect, less bother from jawline and vertical neck bands, and lower psychosocial impact from PP than placebo at Day 14 (P < .0001). OnabotulinumtoxinA effectively improved self-perceived jawline definition and was well tolerated.

Conclusions

OnabotulinumtoxinA was well tolerated and effective at improving moderate to severe PP, including neck bands and jawline definition.

Level of Evidence: 1 (Therapeutic)
Ultraviolet radiation is not the major cause of melanoma mortality in the UK and sun exposure advice should be revised
Authors: Weller Richard B , Gu Jiayue
Published: October 2024

Melanoma has the highest mortality of all skin cancers and efforts to reduce this are focused on sun avoidance. Current UK guidance suggests that 86% of melanomas could be prevented by sun avoidance, which is considerably more than the 72% of lung cancers attributed to cigarette smoking. Unfortunately, the data on which the attributable risk of melanoma to sunlight are based are either speculative or incorrect and recent advances show that they and our approach to preventing melanoma deaths must be reconsidered.
Significant spatial variation of upper crustal anisotropy in Southern Sichuan Basin, China: constraints from local shear wave splitting analysis
Authors: Qiang Zhengyang , Wu Qingju , Li Yonghua
Published: October 2024

The recent upsurge in seismic activity within the southern Sichuan Basin has garnered considerable public attention and simultaneously offers a valuable opportunity for investigating upper crustal anisotropy. Such investigations can provide critical insights into the stress field and crustal deformation in the region. We obtained a total of 1845 high-quality local shear wave splitting measurements at 15 stations and 2027 null measurements at 19 stations. These results indicate the presence of a single layer of anisotropy with a horizontal axis of symmetry at a depth of 3 to 7 km. The fast polarization directions display discernible spatial variations that are primarily influenced by the geographical location of earthquakes rather than changes over time. In the vicinity of the Baimazhen Syncline, the fast polarization directions coincide with the strike of the stratum, forming a circular pattern around the core of the syncline, suggesting that the observed anisotropy is structure-controlled. In contrast, stations situated in the southern Weiyuan Anticline and western Baimazhen Syncline display fast directions trending N171.7 °E and N45.9 °E, respectively. These directions are consistent with the P axes of the focal mechanism of earthquakes, signifying that the anisotropy in these areas is governed by the regional stress field. The findings of this study not only deepen our understanding of the intricate geological structures in the southern Sichuan Basin, but also indicate the need for greater caution when interpreting potential temporal changes in anisotropy in future research.
Arabidopsis KNS3 and its two homologs mediate endoplasmic reticulum-to-plasma membrane traffic of boric acid channels
Authors: Zhang Zhe , Nakamura Shunsuke , Yamasaki Arisa , Uehara Masataka , Takemura Shunsuke , Tsuchida Kohei , Kamiya Takehiro , Shigenobu Shuji , Yamaguchi Katsushi , Fujiwara Toru , Ishiguro Sumie , Takano Junpei
Published: October 2024

Membrane proteins targeted to the plasma membrane are first transported from the endoplasmic reticulum (ER) to the Golgi apparatus. This study explored the mechanisms controlling plasma membrane trafficking of the boric acid channel AtNIP5;1 from the ER. Imaging-based screening using transgenic Arabidopsis identified six mutants in which GFP-NIP5;1 was localized in the ER in addition to the plasma membrane. Genetic mapping and whole-genome resequencing identified the responsible gene in four among the six mutants as KAONASHI3 (KNS3)/SPOTTY1/IMPERFECTIVE EXINE FORMATION. Among the plasma membrane-localized proteins tested, NIP5;1 and its homolog NIP6;1 were retained in the ER of the kns3 mutants. Our genetic analysis further discovered that two homologs of KNS3, KNSTH1 and KNSTH2, were also involved in the ER exit of NIP5;1. In Arabidopsis protoplasts and tobacco leaves, mCherry-fused KNS3 localized to the ER and Golgi, whereas KNSTH2 localized to the ER. The cytosolic C-terminal tail of KNS3 contains amino acids important for Golgi-to-ER trafficking. Furthermore, the ER-to-Golgi trafficking of KNS3 depended on KNSTH1 and KNSTH2, and the accumulation of these three proteins in Arabidopsis roots depended on each other. We propose that KNS3, KNSTH1, and KNSTH2 function as a cargo-receptor complex mediating the ER exit of NIP5;1.
A dark standard siren measurement of the Hubble constant following LIGO/Virgo/KAGRA O4a and previous runs
Authors: Bom C R , Alfradique V , Palmese A , Teixeira G , Santana-Silva L , Santos A , Darc P
Published: October 2024

We present a new constraint on the Hubble constant ($H_0$) from the standard dark siren method using a sample of five well-covered gravitational wave (GW) alerts reported during the first part of the fourth observing run of the Laser Interferometer Gravitational-Wave Observatory (LIGO), the Virgo and Kamioka Gravitational Wave Detector (KAGRA) collaborations (LVK) and with three updated standard dark sirens from third observation run in combination with the previous constraints from the first three runs. Our methodology relies on the galaxy catalogue method alone. We use a deep learning method to derive the full probability density estimation of photometric redshifts using the Legacy Survey catalogues. We add the constraints from well localized binary black hole mergers to the sample of standard dark sirens analysed in our previous work. We combine the $H_0$ posterior for 5 new standard sirens with other 10 previous events (using the most recent available data for the five novel events and updated three previous posteriors from O3), finding $H_0 = 70.4^{+13.6}_{-11.7}~{\rm km~s^{-1}~Mpc^{-1}}$ (68 per cent confidence interval) with the catalogue method only. This result represents an improvement of $\sim 23~{{\ \rm per\ cent}}$ comparing the new 15 dark siren constraints with the previous 10 dark siren constraints and a reduction in uncertainty of $\sim 40~{{\ \rm per\ cent}}$ from the combination of 15 dark and bright sirens compared with the GW170817 bright siren alone. The combination of dark and bright siren GW170817 with recent jet constraints yields $H_0$ of $68.0^{+4.4}_{-3.8}~{\rm km~s^{-1}~Mpc^{-1}}$, a $\sim 6~{{\ \rm per\ cent}}$ precision from standard sirens, reducing the previous constraint uncertainty by $\sim 10~{{\ \rm per\ cent}}$.
Variational inference for acceleration of SN Ia photometric distance estimation with BayeSN
Authors: Uzsoy Ana Sofía M , Thorp Stephen , Grayling Matthew , Mandel Kaisey S
Published: October 2024

Type Ia supernovae (SNe Ia) are standarizable candles whose observed light curves can be used to infer their distances, which can in turn be used in cosmological analyses. As the quantity of observed SNe Ia grows with current and upcoming surveys, increasingly scalable analyses are necessary to take full advantage of these new data sets for precise estimation of cosmological parameters. Bayesian inference methods enable fitting SN Ia light curves with robust uncertainty quantification, but traditional posterior sampling using Markov Chain Monte Carlo (MCMC) is computationally expensive. We present an implementation of variational inference (VI) to accelerate the fitting of SN Ia light curves using the BayeSN hierarchical Bayesian model for time-varying SN Ia spectral energy distributions. We demonstrate and evaluate its performance on both simulated light curves and data from the Foundation Supernova Survey with two different forms of surrogate posterior–a multivariate normal and a custom multivariate zero-lower-truncated normal distribution–and compare them with the Laplace Approximation and full MCMC analysis. To validate of our variational approximation, we calculate the Pareto-smoothed importance sampling diagnostic, and perform variational simulation-based calibration. The VI approximation achieves similar results to MCMC but with an order-of-magnitude speed-up for the inference of the photometric distance moduli. Overall, we show that VI is a promising method for scalable parameter inference that enables analysis of larger data sets for precision cosmology.
A Comparison of Different Strategies for Optimizing the Selection of Empiric Antibiotic Therapy for Pneumonia Caused by Gram-Negative Bacteria in Intensive Care Units: Unit-Specific Combination Antibiograms Versus Patient-Specific Risk Factors
Authors: Wangchinda Walaiporn , Aitken Samuel L , Klatt Megan E , Lephart Paul R , Smith Aaron B , Pogue Jason M
Published: October 2024

Background

Guidelines suggest dual antipseudomonal therapy for empiric treatment of pneumonia caused by gram-negative bacteria in intensive care unit (ICU) patients. Additionally, consideration of local susceptibility data and patient-specific risk factors for resistance is recommended for selecting optimal empiric regimens. However, data assessing how to best do this are lacking, and it is unclear whether a local susceptibility data–based or a patient-specific risk factor–based approach will better drive appropriate empiric treatment. This study aims to compare these 2 strategies.

Methods

This retrospective study was divided into 2 periods. In period I, gram-negative respiratory cultures from ICU patients were used to develop unit-specific combination antibiograms, and individual patient charts were reviewed to assess the impact of risk factors on antimicrobial susceptibility to develop a risk factor–based treatment algorithm. Optimal empiric regimens based on these 2 strategies were then defined. In period II, these regimens were hypothetically applied to patients to compare rates of appropriate empiric therapy and overuse by the 2 methods.

Results

Risk factor–based regimens had a higher appropriateness rate compared to regimens derived from antibiograms (89.9% vs 83.7%). Additionally, applying antibiogram-based regimens resulted in a higher prevalence of antibiotic overuse than a patient-specific risk factor–based approach (69.8% vs 40.3%), with excess overuse driven by a higher frequency of unnecessary use of combination therapy.

Conclusions

Both strategies provided high rates of appropriateness in empiric antibiotic selection. However, the patient-specific risk factor–based approach demonstrated a higher rate of appropriate therapy and offered advantages in reducing rates of unnecessary combination therapy.
T-cell and Soluble Co-inhibitory Receptor Expression in Patients With Visceral Leishmaniasis Are Markers of Treatment Response and Clinical Outcome
Authors: Ademe Muluneh , Osorio Yaneth , Fikre Helina , Adane Desalegn , Mulaw Tadele , Travi Bruno L , Howe Rawliegh , Hailu Asrat , Abebe Tamrat , Melby Peter C
Published: October 2024

Background

Co-inhibitory receptors (immune checkpoints) regulate activated immune cells. Their expression on T cells can limit host defense. We hypothesized that chronic Leishmania donovani infection in patients with visceral leishmaniasis (VL) leads to expression of co-inhibitory receptors that could be markers of treatment response and clinical outcome.

Method

A prospective cohort of 21 subjects with VL (7 with HIV coinfection) and 10 controls was established to measure T-cell expression of co-inhibitory receptors (PD-1, Tim-3, LAG-3, CTLA-4, and TIGIT) by flow cytometry in discarded remnants of diagnostic splenic or bone marrow aspirates and peripheral blood collected before and after treatment. Plasma levels of soluble co-inhibitory proteins (sPD-1, sTim-3, sLAG-3, and sCTLA-4) and selected cytokines were determined by immunoassay.

Results

Expression of co-inhibitory receptors in peripheral blood T cells generally reflected findings in spleen and bone marrow aspirates. PD-1 and Tim-3 were upregulated in CD4+ T cells in HIV-negative and HIV-positive subjects with VL compared to controls. CD8+ T cells from HIV-negative subjects with VL displayed a similar pattern. Plasma levels of sPD-1 and sTim-3 were also greater in VL patients than controls. CD8+ and CD4+ T cells coexpressing PD-1 and Tim-3 showed considerable decline with treatment. Mortality in HIV-negative VL patients was associated with increased CD8+ T cells coexpressing Tim-3 and PD-1, triple-positive CD4+ and CD8+ T cells (PD-1+Tim-3+LAG-3+), and elevated sLAG3.

Conclusions

Tim-3 and PD-1 expression on CD4+ and CD8+ T cells, and increased plasma sLAG-3, were markers of treatment response and clinical outcome in patients with VL.
Jurisdiction and Afro-Brazilian Legal Politics from Colonialism to Early Independence
Authors: Richards Jake Subryan
Published: October 2024

Every empire in the Americas developed a law of slavery that connected the forced transoceanic migration of enslaved people with land-based economic production and social life. Competing conceptions of jurisdiction over land and sea emerged from legal processes regarding slavery in the transition from colonial Portuguese rule to early independence in Brazil. Both the Portuguese monarch and post-independence Brazilian ministers sought to assert jurisdiction over residents inside the territory, including enslaved people. Their attempts to do so created social conflicts in which enslaved people put forth their own visions of jurisdiction and justice. Afro-Brazilian people developed a legal politics that drew upon diasporic maritime connections to overturn enslavement. The legal politics of cases regarding uprisings and contraband slave-trading animated concerns among judges and imperial administrators about effective legal order. A revolutionary movement in 1798 contested Portuguese colonial sovereignty with a vision of free-trade popular sovereignty. The monarch’s transfer from Portugal to Brazil in 1808 opened a small route for enslaved people to petition the crown for freedom based on innovative readings of free soil. A major case of capture in 1851 illuminated how the naval court judge adjudicated the case as the capture of an enemy. Captive African people testified in court to gain collective freedom in a liminal space. These claims to freedom raised important questions about legal equality and freedom from illegal trafficking for all people held in slavery in Brazil.
The Return of the Repressed: Political Deportation in the  Indian Ocean during the Age  of Revolutions
Authors: Morieux Renaud
Published: October 2024

Between the second half of the eighteenth and the beginning of the nineteenth century, the Indian Ocean became a theatre of the global war waged by European imperial states. This article compares how three colonial powers, in French, Danish, and British colonial territories, dealt with interconnected political threats, in a region where the limits of imperial sovereignty and jurisdictions were often blurred and frequently renegotiated. Rather than a formally sanctioned doctrine and legal category, deportation should be understood as a crude tool for solving a variety of problems. Although the forced removal of criminals, religious minorities or political opponents was not a new instrument to the late eighteenth century, it is often ignored that political deportation was also a widely used legal practice in the Indian Ocean during the ‘age of revolutions’. In this region, deportation was used by imperial centres to get rid of political enemies, but also by regional authorities, without referring to metropolitan orders. It was usually not a judicial punishment, but an administrative measure justified in the name of political necessity. This article focuses on three small colonial enclaves, French Reunion, Danish Tranquebar, and British Pondicherry, where a siege mentality and fear of political sedition were omnipresent in this period. Contemporaries believed, with some justifications, that a single conspiracy linked these three colonial theatres, involving the same set of protagonists, who redeployed their projects as they were removed from one place to the next. But in these three sites and societies, deportation raises different issues. Dumping radicals on a foreign shore might have been a short-term fix, but it rarely solved problems in the long term: deportees often returned after some time, which was a direct consequence of the colonial authorities’ reluctance to take irreparable decisions, and of the entanglement of empires and polities in the Indian Ocean.
Comparative effects of biological and targeted synthetic DMARDs on incident chronic kidney disease in patients with rheumatoid arthritis
Authors: Nishimura Nozomi , Onishi Akira , Yamamoto Wataru , Nagai Koji , Shiba Hideyuki , Okita Yasutaka , Son Yonsu , Amuro Hideki , Okano Takaichi , Ueda Yo , Hara Ryota , Katayama Masaki , Yamada Shinsuke , Hashimoto Motomu , Maeda Yuichi , Onizawa Hideo , Fujii Takayuki , Murata Koichi , Murakami Kosaku , Tanaka Masao , Matsuda Shuichi , Morinobu Akio
Published: October 2024

Objectives

The impact of individual biological/targeted synthetic DMARD (b/tsDMARD) on kidney function in patients with RA remains unclear. This study aimed to determine the comparative effects of b/tsDMARDs on chronic kidney disease (CKD) incidence in patients with RA.

Methods

This multicentre cohort study included patients with RA who had baseline estimated glomerular filtration rate (eGFR) of ≥60 ml/min/1.73 m2 and started a TNF inhibitor (TNFi), cytotoxic T-lymphocyte-associated antigen-4-Ig (CTLA4-Ig), interleukin-6 receptor inhibitor, or Janus kinase inhibitor (JAKi) in Japan. Multiple propensity score-based inverse probability weighting (IPW) was used to adjust confounders. The incidence of CKD was compared among b/tsDMARDs using IPW mixed-effect Cox proportional hazards models and linear mixed-effect models with IPW-examined trajectories of eGFR.

Results

Among 2187 patients with 3068 treatment courses and up to 11 years of follow-up, CKD occurred in 275 cases. Compared with the CTLA4-Ig group, the TNFi group had a significantly lower CKD incidence [hazard ratio (HR) 0.67, 95% CI 0.46–0.97, P = 0.04], whereas the JAKi group had a significantly higher incidence (HR 2.16, 95% CI 1.23–3.79, P = 0.01). The trajectory of eGFR was significantly greater in the JAKi group than in the CTLA4-Ig group (CTLA4-Ig: −1.28 ml/min/1.73 m2/year, JAKi: −2.29 ml/min/1.73 m2/year, P < 0.001).

Conclusions

TNFi use was associated with reduced CKD incidence, whereas JAKi showed a less protective association for kidney function in patients with RA.
Sympatric populations of crop and wild carrots (Daucus carota ssp.) have distinct viromes, with shared core species more prevalent in farm-grown populations
Authors: Schönegger Deborah , Marais Armelle , Garcia Arenal Fernando , Malmstrom Carolyn M. , Martinez Jimenez Marcos , McLeish Michael , Lefebvre Marie , Faure Chantal , Svanella-Dumas Laurence , Candresse Thierry
Published: October 2024

Viral exchanges between crops and wild plants are important considerations in virus ecology and epidemiology but remain poorly understood. To investigate such exchanges, we compared the viromes of wild and farmed carrots (Daucus carota ssp.) growing near each other in France. Farm populations included cultivated varieties and off-type carrots (resembling wild ones) growing among them. This crop - wild relative pathosystem offers notable opportunities for virus exchange due to the hosts’ genetic closeness and geographic proximity. High-throughput sequencing found that viral taxonomic richness was greatest in wild carrots. However, hierarchical clustering and bipartite network analyses revealed that wild and farm carrot viromes differed in their seed-borne and vector-borne components. While ~50% of viral taxa were shared among carrot population types, others were uniquely associated with either wild or farm carrots. Individual-plant RT-PCR testing of 16 aphid-borne agents from the shared core virome found their prevalence was generally greatest in farm populations, with some geographic variability in virus pressure. The viromes of off-type and cultivated carrots were most similar, suggesting that proximity and/or management practices influence virome properties. For some aphid-borne viruses, similar isolates were found in wild and cultivated carrots, suggesting exchanges between them or with a shared source. However, isolates of other aphid-borne viruses clustered by carrot type, indicating barriers to viral fluxes, that might involve differential susceptibility of populations, vector preferences, or unidentified factors. To improve virus management, we need better understanding of how specific facilitators and barriers of viral exchange can be manipulated to reduce negative viral impacts.
Postharvest chitosan sprays reduce bitter rot and blue mold on apple fruit
Authors: DeGenring Liza M. , Peter Kari , Poleatewich Anissa M.
Published: October 2024

Chitosan is a natural product that has potential use in agriculture for managing diseases. Chitosan has been shown to effectively suppress storage rots when applied postharvest. Application of chitosan pre- and postharvest has potential to manage both latent and postharvest rots but these effects are not well studied. Furthermore, to determine the most effective strategy for using chitosan to manage apple diseases, research on application rates, chitosan molecular weight, phytotoxicity potential, and formulation is needed. The objectives of this study were to (1) identify non-phytotoxic concentrations of chitosan on apple fruit; (2) evaluate commercial chitosan products for reduction of postharvest disease severity on inoculated fruit; (3) evaluate the effect of pre-harvest chitosan applications on suppression of latent infections, postharvest rots, and fruit quality; and (4) evaluate the effect of pre-harvest plus postharvest chitosan applications on suppression of Penicillium expansum and Colletotrichum fioriniae on inoculated fruit. Under lab conditions, chitosan products applied at higher rates were more effective at reducing disease but tended to cause phytotoxicity. This phytotoxic effect was remediated when the product’s pH was adjusted to ~5. Tidal Grow products applied at 1.0% (v/v) chitosan reduced lesion size caused by P. expansum and C. fioriniae on inoculated apples up to 86% compared to a water treatment. Pre-harvest applications of chitosan and Serenade ASO reduced bitter rot up to 85% on immature fruit in a research orchard. The results from this research suggest that Tidal Grow adjusted to pH ~5 can reduce postharvest diseases of apple fruit.
Confirmation of Candidatus Liberibacter asiaticus in Asian Citrus Psyllids and Detection of Asian Citrus Psyllids in Commercial Citrus in Georgia (U.S.A.)
Authors: Collins Carlton , Oliver Jonathan E. , Barman Apurba , Munoz Gabriel , Jimenez Madrid Alejandra M.
Published: October 2024

The Asian citrus psyllid (ACP) is the vector of Candidatus Liberibacter asiaticus (CLas), the causal agent of citrus greening or Huanglongbing (HLB), one of the most devastating citrus diseases worldwide. The citrus industry in Georgia (U.S.A.) is in the process of a rapid expansion, and based on experiences with HLB in Florida, there is great concern about the potential impacts of HLB on this emerging industry. Prior to 2023, ACP had been identified in residential citrus trees in isolated Georgia counties but little to no testing of psyllids for CLas had occurred. However, in 2023, one individual psyllid collected from Chatham County was confirmed positive for CLas by PCR and sequencing. Furthermore, during 2023, ACP adults and nymphs were identified for the first time in a Georgia commercial citrus grove. The finding of ACP in a commercial planting represents a significant risk for CLas dissemination, and thereby has the potential to stall the rapid expansion of Georgia’s citrus industry. In the coming years, surveillance and testing of ACP from commercial groves will be essential for the early detection and management of HLB and its vector to reduce HLB spread within Georgia’s commercial groves.
Ten-Year Follow-Up After Descemet Membrane Endothelial Keratoplasty
Authors: Teubert Selina , Borgardts Klara , Steindor Friedrich , Borrelli Maria , Schrader Stefan , Geerling Gerd , Spaniol Kristina
Published: October 2024

Purpose:

To examine clinical results up to 10 years after Descemet Membrane Endothelial Keratoplasty (DMEK) and Triple-DMEK.

Methods:

Prospective study including 201 eyes, of which 54 eyes [38 DMEKs and 16 Triple-DMEKs; Fuchs endothelial dystrophy (n = 45), pseudophakic bullous keratopathy (n = 9)] reached the minimum follow-up of 5 years and were followed up for up to 10 years. We evaluated best-corrected visual acuity (BCVA, logarithm of the minimum angle of resolution [logMAR]), endothelial cell density (ECD, cells/mm2), minimal central corneal thickness (CCT, μm), central retinal thickness (μm), rebubbling, graft survival and re-DMEK rate, chamber angle alterations, and incidence of glaucoma.

Results:

Fifty-four eyes had a 5-year and 37 eyes an 8- to 10-year follow-up. Mean follow-up was 94.4 ± 12.1 months. Best-corrected visual acuity increased from 0.6 ± 0.3 logMAR to 0.1 ± 0.2 logMAR at 6 months (P ≤ 0.001) and was 539 ± 54 μm at long term. Endothelial cell density decreased from 2488 ± 320.9 (donor) to 980.1 ± 437 cells/mm2 with an average ECD loss/year of 4% and did not correlate with BCVA. Central corneal thickness decreased from 596.9 ± 82.2 μm to 498.6 ± 24.3 μm at 12 months (P ≤ 0.001) and remained stable (P = 1.000). Mean rebubbling rate was 0.3 ± 0.5/eye and did not correlate with BCVA. Eight eyes (14.8%) received at least 1 rebubbling. Primary graft failure/rejection rate was 1.5%/0% within the first postoperative year, and secondary graft failure rate was 12.4% at 7 years. Eight eyes (preoperative n = 3, de novo n = 5) had open-angle glaucoma without chamber angle changes (14.8%, P ≤ 0.001).

Conclusions:

Although ECD decreases continuously in the long-term follow-up, excellent visual acuity can be preserved 10 years after DMEK and Triple-DMEK. The final outcome can be estimated 6 months after surgery.
Efficacy and safety of coronary sinus reducer for refractory angina: a systematic review and meta-analysis of randomized controlled trials
Authors: Amin Ahmed Mazen , Khan Ubaid , Khlidj Yehya , Katamesh Basant E. , Elbenawi Hossam , Ewis Abdelrahman , Hammad Amer
Published: October 2024

Refractory angina affects patients’ quality of life around the world. Coronary sinus reducer (CSR) is a new therapeutic approach that has been investigated in recent years. We aimed to investigate the efficacy and safety of CSR for refractory angina. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) from PubMed, Web of Science, Scopus, Embase, and CENTRAL searches until May 2024. Dichotomous data were pooled using risk ratio (RR), and continuous data were pooled using mean difference (MD), both with a 95% confidence interval (CI), using (R version 4.3). With the inclusion of three RCTs, our cohort comprised a total of 180 patients. Compared with the control group, after 6 months, CSR was significantly associated with a decreased mean change of Canadian Cardiovascular Society (CCS) class [MD: −0.54 with 95% CI (−0.80 to −0.27), P < 0.01], a decreased number of patients in the CCS class III/IV [RR: 0.56 with 95% CI (0.38–0.84), P < 0.01], and increased exercise time [MD: 50.46 with 95% CI (9.47–91.45), P = 0.02]. However, there was no significant difference between CSR and the control group in double products, all Seattle Angina Questionnaire domains, and safety outcomes. CSR has been shown to reduce angina severity by lowering CCS class scores and increasing exercise time. Large-scale RCTs are needed to confirm its effectiveness in patients with refractory angina.
Reactive oxygen species and neurodegenerative diseases: insights into nanozyme therapeutics
Authors: Wang Luo , Chen Feixiang , Zhang Cuiling , Cheng Yuen Yee , Bu Wenbo , Liu Yanyan
Published: October 2024

Oxidative stress plays a critical role in the onset and progression of neurodegenerative diseases. Traditional methods for regulating oxidative stress using drugs or enzyme molecules often face limitations in efficacy, potential side effects, and the ability to fully meet clinical needs. The emergence of nanozymes offers a novel approach to overcome these challenges and explore therapeutic mechanisms. Focusing on the interaction between reactive oxygen species (ROS) and the nervous system, this article reviews the latest advancements in the use of nanozymes for treating neurodegenerative diseases. First, the mechanism of ROS interaction with neurons and glial cells in the complex nervous network is summarized by analyzing the characteristics of ROS. Second, the application examples and mechanism exploration of different types of ROS-related nanozymes in many neurodegenerative diseases are introduced and summarized. Additionally, the current situation and future prospects of nanozymes combined with advanced technologies such as in vitro detection and artificial intelligence for disease treatment are further discussed. This approach is poised to significantly advance the development of therapies for neurodegenerative diseases.
Integrated manual therapies: IASP taskforce viewpoint
Authors: Draper-Rodi Jerry , Newell Dave , Barbe Mary F. , Bialosky Joel
Published: October 2024

Introduction:

Manual therapy refers to a range of hands-on interventions used by various clinical professionals, such as osteopaths, osteopathic physicians, chiropractors, massage therapists, physiotherapists, and physical therapists, to treat patients experiencing pain.

Objectives:

To present existing evidence of mechanisms and clinical effectiveness of manual therapy in pain.

Methods:

This Clinical Update focuses on the 2023 International Association for the Study of Pain Global Year for Integrative Pain Care. Current models of manual therapy and examples of integrative manual therapy are discussed.

Results:

The evolution of concepts in recent years are presented and current gaps in knowledge to guide future research highlighted. Mechanisms of manual therapy are discussed, including specific and contextual effects. Findings from research on animal and humans in manual therapy are presented including on inflammatory markers, fibrosis, and behaviours. There is low to moderate levels of evidence that the effect sizes for manual therapy range from small to large for pain and function in tension headache, cervicogenic headache, fibromyalgia, low back pain, neck pain, knee pain, and hip pain.

Conclusion:

Manual therapies appear to be effective for a variety of conditions with minimal safety concerns. There are opportunities for manual therapies to integrate new evidence in its educational, clinical, and research models. Manual therapies are also well-suited to fostering a person-centred approach to care, requiring the clinician to relinquish some of their power to the person consulting. Integrated manual therapies have recently demonstrated a fascinating evolution illustrating their adaptability and capacity to address contemporary societal challenges.
Three-dimensional facial morphology in patients with craniofacial microsomia and microtia
Authors: Ronde Elsa M. , de Jong Guido A. , Nolte Jitske W. , Nienhuijs Marloes E.L. , Bulstrode Neil W. , Maal Thomas J.J. , Becking Alfred G. , Breugem Corstiaan C. ,   the 3DCFMM research consortium*
Published: October 2024

Introduction:

Craniofacial microsomia (CFM) is classified using the subjective Orbit, Mandible, Ear, Nerve and Soft tissue (OMENS) tool. Digital stereophotogrammetry (i.e. three-dimensional [3D] photography) can be used to capture facial shape objectively. This case-control study assessed the applicability of 3D photography in distinguishing between patients with CFM and individuals without craniofacial conditions, as well as classifying the severity of facial involvement.

Methods:

3D photographs of patients with CFM and/or microtia from the Amsterdam UMC, Radboudumc and the Great Ormond Street Hospital and of individuals without craniofacial conditions were assessed. Differences between patients and controls were explored through asymmetry index (ASI) and facial signature (FS) scores, as well as a principal components (PC) analysis of FS scores and logistic regression. Correlations between OMENS scores and ASI, FS and PC scores were evaluated.

Results:

A total of 179 patients and 210 controls were analyzed. ASI and FS scores differed significantly between patients and controls (p<0.001), and were correlated with several OMENS subscales. The logistic regression model distinguishing between patients and controls showed increasing asymmetry of the mandible and orbits with increasing Pruzansky-Kaban score. Patients with isolated microtia deviated from controls in the midface.

Conclusion:

Clinically significant differences in the facial morphology of patients with CFM and microtia were found compared to controls, suggesting that 3D photography can be used to assess the severity of facial involvement in a novel, objective and safe way in these patients.
Markers of T-cell dysfunction and not inflammaging predict the waning of humoral responses to SARS-CoV-2 mRNA booster vaccination in people with HIV
Authors: Augello Matteo , Bono Valeria , Rovito Roberta , Santoro Andrea , Tincati Camilla , Marchetti Giulia
Published: October 2024

In this prospective longitudinal study, we evaluated the durability of humoral responses to SARS-CoV-2 mRNA booster vaccination in 93 people with HIV, exploring the possible role of T-cell dysfunction and inflammaging biomarkers in predicting antibody waning. We found that, despite a negligible influence of the inflammaging milieu, low CD4/CD8 ratio and CD4+CD127+ percentage as well as high CD8+CD38+CD45RO+ percentage are associated with faster antibody waning, in turn contributing to our understanding of the determinants of COVID-19 vaccine-elicited immune response in this population.
Gone but not forgotten: dynamics of sperm storage and potential ejaculate digestion in the black soldier fly
Hermetia illucens
Authors: Manas Frédéric , Piterois Harmony , Labrousse Carole , Beaugeard Laureen , Uzbekov Rustem , Bressac Christophe
Published: October 2024

Understanding the dynamics of sperm storage is essential to unravel the complexity of post-copulatory sexual selection processes in internally fertilized species. This physiological process goes from sperm transfer during copulation to its use for fertilization. In this context, the spatiotemporal dynamics of sperm storage were described in the black soldier fly (BSF) with fluorescence and transmission electron microscopy (TEM). BSF females have compartmentalized spermathecae with a transfer compartment, the fishnet canals, and a storage compartment, the reservoirs. Spermatozoa were counted both during and after mating in the two compartments. In addition to seminal fluids, the male transfers a mass of sperm in the fishnet canals, then only 49% of the transferred spermatozoa reach the reservoirs over two days. TEM observations of the fishnet canals revealed potential digestive functions, explaining the decline in the number and viability of spermatozoa in this compartment but not in the reservoirs. After one mating, females laid up to three fertile clutches, showing no constraints on sperm quantity or quality. Spermatic and ultrastructural investigations strongly suggest that BSF ejaculate acts both as a sperm plug and as a nuptial gift, reinforcing the interest in studying this farming insect as a new model for sexual selection.
Warming reduces mid-summer flowering plant reproductive success through advancing fruiting phenology in an alpine meadow
Authors: Zhang Tianwu , Chen Yaya , Yang Xiangrong , Zhang Hui , Guo Zengpeng , Hu Guorui , Bai Haonan , Sun Yinguang , Huang Li , Ma Miaojun
Published: October 2024

Changes in reproductive phenology induced by warming are happening across the globe, with significant implications for plant sexual reproduction. However, the changes in plant reproductive output (number of flowers and fruits) and success (successful fruits/total flowers) in response to climate change have not been well characterized. Here, we conducted a warming and altered precipitation experiment in an alpine meadow on the eastern Tibetan Plateau to investigate the effects of climate change on the reproductive phenology and success of six common species belonging to two flowering functional groups. We found that warming advanced the start of flowering and the start of fruiting in mid-summerflowering plants. Warming reduced the reproductive output of early-spring flowering plants but did not change their reproductive success. The effects of warming and altered precipitation on the reproductive output and success of mid-summer flowering plants were year-dependent, and the fruiting phenology regulated the response of the mid-summer flowering plant’s reproductive success to climate change. These findings highlight the critical role of fruiting phenology in the reproductive success of alpine plants and imply that alpine plants may reduce their fitness by producing fewer flowers and fruits under climate warming, especially for later flowering plants.
Paracoccus spongiarum sp. nov., isolated from the marine sponge, Phakellia elegans
Authors: Kim Soo-Bin , Kim Kyung Hyun , Park Jin-Sook
Published: October 2024

A facultative anaerobic Gram-negative bacterium, designated as strain 2205BS29-5T, was isolated from a marine sponge, Phakellia elegans, in Beomseom on Jeju Island, Republic of Korea, and taxonomically characterized. The cells were catalase and oxidase positive, non-motile, coccoid-rod shaped and capable of poly-β-hydroxybutyrate production. Growth was observed at 10–37 °C (optimum, 25 °C) and pH 5.0–8.0 (optimum, pH 7.0), and in the presence of 0–9% NaCl (w/v) (optimum, 3.0–4.0%). The major cellular fatty acids and respiratory quinone were identified as summed feature 8 (C18 : 1
 ω7c/C18 : 1
 ω6c) and Q-10, respectively. The major polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, four phosphoglycolipids, two unidentified amino lipids and eight unidentified lipids. The DNA G+C content was 67.8%. Strain 2205BS29-5T was most closely represented by Paracoccus amoyensis 11-3T and P. caeni MJ17T with 97.8 and 97.5% 16S rRNA gene sequence similarities, respectively. Phylogenetic analyses based on 16S rRNA genes and whole-genome sequences showed that strain 2205BS29-5T was affiliated with the genus Paracoccus. Genomic analysis showed that strain 2205BS29-5T could synthesize vitamin B family (folate and cobalamin) and ectoine. The average nucleotide identity and digital DNA–DNA hybridization values between strain 2205BS29-5T and P. amoyensis 11-3T were 77.1% and 18.8%, respectively, and with P. caeni MJ17T were 78.4 and 21.2%, respectively. Based on phylogenetic, chemotaxonomic and genome relatedness analyses, strain 2205BS29-5T represents a novel species of the genus Paracoccus, for which the name Paracoccus spongiarum sp. nov. is proposed. The type strain is 2205BS29-5T (=LMG 33062T =KACC 23240T).
BALB/c mice challenged with SARS-CoV-2 B.1.351 β variant cause pathophysiological and neurological changes within the lungs and brains
Authors: Saenkham-Huntsinger Panatda , Drelich Aleksandra K. , Huang Pinghan , Peng Bi-Hung , Tseng Chien-Te K.
Published: October 2024

Up to one-third of individuals suffering from acute SARS-CoV-2 infection with the onset of severe-to-mild diseases could develop several symptoms of neurological disorders, which could last long after resolving the infection, known as neuro-COVID. Effective therapeutic treatments for neuro-COVID remain unavailable, in part, due to the absence of animal models for studying its underlying mechanisms and developing medical countermeasures against it. Here, we explored the impact of SARS-CoV-2 infection on the well-being of respiratory and neurological functions of BALB/c mice by using a clinical isolate of β-variant, i.e. B.1.351. We found that this β-variant of SARS-CoV-2 primarily infected the lungs, causing tissue damage, profound inflammatory responses, altered respiratory functions and transient but significant hypoxia. Although live progeny viruses could not be isolated, viral RNAs were detected across many anatomical regions of the brains in most challenged mice and triggered activation of genes encoding for NF-kB, IL-6, IP-10 and RANTES and microglial cells. We noted that the significantly activated IL-6-encoded gene persisted at 4 weeks after infection. Together, these results suggest that this B.1.351/BALB/c model of SARS-CoV-2 infection warrants further studies to establish it as a desirable model for studies of neuropathogenesis and the development of effective therapeutics of neuro-COVID.
A comparative study of multidrug resistant bacteria (MDRB) isolated from various patients in different wards of a hospital during post Covid-19
Authors: Ojha Abhishek , Figueiredo Dwight , Khan Shabnum
Published: October 2024

Antibacterial resistance is an alarming global concern and a public health challenge of the twenty-first century for which effective systems are required to track and treat ABR. We performed microbiological and antibiotic susceptibility testing on the samples to detect and characterize Multidrug-Resistant Bacteria (MDRB) isolated from patients segregating MDRB characteristics (types, prevalence and distribution of MDRB) based on time (i.e., during versus post covid-19) and location (i.e., different wards of a tertiary care hospital). We observed an increase of MDRB in 2022 as compared to 2021 and 2023. These MDRB had a Shannon and Simpson index values of 1.138 to 1.508 and 0.643 to 0.775, respectively and an observed evenness values of 0.780 to 1.042, which revealed the microbial diversity recovered from the patient samples. In keeping with previous MDR studies,Klebsiella,E.coli,Citrobacter,AcinetobacterandPseudomonaswere identified from the patient samples. Moreover, compared to previous reports, the percentage of MDR-bacteria, i.e.,Klebsiella(40 %),E.coli(28 %), andCitrobacter(19 %), populations were higher in this study. We observed that Gamma-proteobacteria were predominant across all the recovered samples, and thatAcinetobacterandKlebsiellaisolated from the samples were 100 % resistant to twenty and eleven antibiotics, respectively. Furthermore, the fatality rate was low compared with the available reports suggesting possibilities for effective recovery if given rapid and tailored treatment. Given the challenges faced by MDRB strains more surveillance and tracking is needed to ensure effective and specifically targeted treatment strategies.
The plastid-encoded RNA polymerase structures a logistic chain for light-induced photosynthesis
Authors: Gillet François-Xavier , Effantin Gregory , Freiherr von Scholley Gian Luca , Brugière Sabine , Turquand Maud , Pasha Noor , Fenel Daphna , Vallet Alicia , Couté Yohann , Cobessi David , Blanvillain Robert
Published: October 2024

The chloroplast is the semi-autonomous organelle of eukaryotes that performs photosynthesis. In higher plants, chloroplast biogenesis depends on a tight transcriptional coordination of both nuclear- and-plastid photosynthesis-associated genes. The plastid-encoded RNA-polymerase (PEP) is composed of a plastid-encoded catalytic core, similar to multi-subunit RNA polymerases, bound to fifteen nuclear-encoded PEP-associated proteins (PAPs). The binding of all the PAPs to the catalytic core is essential for plastid transcription of photosynthesis-associated genes. Our cryo-electron microscopy structure of the native 21-subunit PEP fromSinapis albareveals the distinctive patterning of PAP interactions, which evolved upon the ancestral cyanobacterial catalytic core acting as a scaffold. Using PAP8in plantaas bait for affinity purification and proximity labeling, we provide the protein landscapes surrounding the PEP and other PAP8-interacting complexes at the transition from skotomorphogenesis to photomorphogenesis. The data highlight multiple functional couplings in which plastid transcription is at the beginning of a spatial logistic chain, extending from transcription to the assembly of the photosynthetic apparatus into the thylakoids. In addition, dark-specific interactions between photoreceptors and PAP8 establish a physical link between an integrated light signaling and plastid functions.
LassoESM: A tailored language model for enhanced lasso peptide property prediction
Authors: Mi Xuenan , Barrett Susanna E. , Mitchell Douglas A. , Shukla Diwakar
Published: October 2024

Ribosomally synthesized and post-translationally modified peptides (RiPPs) comprise a structurally and functionally diverse group of natural products. Lasso peptides represent one of about 50 known molecular classes of RiPPs, which display a characteristic [1] rotaxane conformation formed by a lasso cyclase. This unique, threaded conformation endows lasso peptides with diverse biological activities and remarkable thermal and proteolytic stability. The prediction of lasso peptide properties, such as substrate compatibility with a particular lasso cyclase or desired biological activity, remains challenging due to limited experimental data and the intricate nature of the substrate fitness landscapes. Protein language models (PLMs) have demonstrated impressive performance in predicting protein structure and function. However, general-purpose PLMs perform poorly in lasso peptide-related predictive tasks. Therefore, there is a need to provide effective representations for lasso peptides to enable enhanced property prediction. In this study, we developed a lasso peptide-specific language model (LassoESM) by leveraging advances in pre-trained PLMs to aid the prediction of lasso peptide related properties and experimentally validate the model predictions. We demonstrate that LassoESM embeddings can accurately predict substrate compatibility for a lasso cyclase of interest when experimental data for model training was scarce. Using a deep learning framework incorporating cross-attention between lasso cyclase and substrate peptide embeddings, we identify non-cognate pairs of lasso cyclases and substrate peptides with predicted compatibility. We further show that LassoESM embeddings improve the prediction of RNA polymerase inhibitory activity, which represents a biological activity of several known lasso peptides. We anticipate that LassoESM and future iterations thereof will be instrumental for the rational design of lasso peptides with desired properties.