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Background: Simlukafusp alfa (FAP-IL2v) is an immune cytokine engineered to selectively promote immune responses in the tumour microenvironment. We evaluated the antitumour activity and safety of FAP-IL2v plus atezolizumab in recurrent and/or metastatic cervical squamous cell carcinoma (SCC) in a phase 2 basket study (NCT03386721)., Methods: Patients with confirmed metastatic, persistent or recurrent cervical SCC who had progressed on ≥1 anti-cancer therapy and had measurable disease were enrolled. FAP-IL2v 10 mg was administered once every 3 weeks (Q3W) or once weekly (QW) for 4 weeks then once every 2 weeks (Q2W) with the corresponding Q3W or Q2W atezolizumab regimens. The primary endpoint was objective response rate by investigator assessment., Findings: Forty-eight patients were enrolled (Q3W: n = 47; QW/Q2W: n = 1). Among 45 response evaluable patients, objective responses occurred in 12 patients (27%; CI 16.0-41.0), including 3 complete and 9 partial responses. Responses occurred in 6/19 PD-L1 positive patients (32%; 95% CI 15.4-54.0) and 5/24 PD-L1 negative patients (21%; 95% CI 9.2-35.6). Median duration of response was 13.3 months (95% CI 7.6-NE). Median progression-free survival was 3.7 months (95% CI 3.3-9.0). Adverse events (AEs) were consistent with the known safety profile of each drug. AEs leading to withdrawal of either agent occurred in 6 patients (13%). Pronounced expansion and activation of natural killer and CD8 T cells in peripheral blood and increased tumour infiltration and inflammation were observed., Interpretation: FAP-IL2v plus atezolizumab is clinically active and has manageable safety in patients with recurrent and/or metastatic cervical SCC., Funding: F. Hoffmann-La Roche Ltd., Competing Interests: Declaration of interests L. Verlingue reports grants from Bristol-Myers Squibb; royalties or licenses from RESOLVED; payment or honoraria from Bristol-Myers Squibb; leadership or fiduciary role as CEO of RESOLVED; stock or stock options from RESOLVED; as part of the Drug Development Department (DITEP) of Gustave Roussy and Early Phase Unit of Centre Léon Bérard, L. Verlingue reports being Principal/Sub-Investigator of clinical trials for AbbVie, Adaptimmune, Aduro Biotech, Agios Pharmaceuticals, Amgen, argenx, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca, AVEO pharmaceuticals, Basilea Pharmaceutica, Bayer, BBB Technologies, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers Squibb, Celgene Corporation, Chugai Pharmaceutical Co., Clovis Oncology, Cullinan-Apollo, Daiichi Sankyo, Debiopharm, Eisai, Eli Lilly, Exelixis, Faron Pharmaceuticals, F. Hoffmann-La Roche, Forma Therapeutics, GamaMabs Pharma, Genentech, GlaxoSmithKline, H3 Biomedicine, ImCheck Therapeutics, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Janssen Pharmaceuticals, Kura Oncology, Kyowa Kirin, Loxo Oncology, Lytix Biopharma, Medimmune, Menarini Ricerche, Merck Sharpe & Dohme, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Molecular Partners, Nanobiotix, Nektar Therapeutics, Novartis, Octimet Oncology, Oncoethix, Oncopeptides, Orion Pharma, Ose Pharma, Pfizer, PharmaMar, Pierre Fabre, Medicament, Sanofi, Seattle Genetics, SOTIO, Servier, Syros Pharmaceuticals, Taiho Pharma, Tesaro, and Xencor; research grants from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen Pharmaceuticals, Merck Sharpe & Dohme, Novartis, Onxeo, Pfizer, Roche, and Sanofi; non-financial support (drug supplied) from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Medimmune, Merck Sharpe & Dohme, NH TherAGuiX, Onxeo, and Pfizer. H. Prenen reports payment or honoraria for presentations from Amgen, AstraZeneca, Bayer, Roche, and Sanofi; support for attending meetings from AstraZeneca, Bayer, and Roche; personal fees for participation on a Data Safety Monitoring Board or Advisory Board for Biocartis and Cureteq. E. M. Guerra Alia reports personal consulting fees for AstraZeneca, Clovis Oncology, GlaxoSmithKline, Merck Sharpe & Dohme, PharmaMar, and Roche; payment or honoraria from AstraZeneca (personal), Clovis Oncology, GlaxoSmithKline, Merck Sharpe & Dohme, and PharmaMar; personal payment for expert testimony from AstraZeneca, Clovis Oncology, GlaxoSmithKline, Merck Sharpe & Dohme, PharmaMar, and Roche; personal support for attending meetings and/or travel from AstraZeneca and GlaxoSmithKline. R. Perets reports personal consulting fees for 1Etx, Galmed Therapeutics, and Gilboa Therapeutics; payment or honoraria from Merck Sharpe & Dohme; support for attending meetings and/or travel from Pfizer. I Lugowska reports grants or contracts from Agenus and Roche; personal payment or honoraria from Bristol-Myers Squibb, Novartis, and Merck Sharpe & Dohme; support for attending a meeting and/or travel from ESMO; other financial interests or non-financial interests from Clinnote. A. Taus reports payment or honoraria from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck Sharpe & Dohme, Pfizer, Roche, Sanofi, and Takeda. A. Oaknin reports institutional funding from AbbVie, Advaxis, Aeterna Zentaris, Amgen, Aprea Therapeutics, Bristol-Myers Squibb, Clovis Oncology, Eisai, Immunogen, Merck Sharpe & Dohme, Millennium Pharmaceuticals, PharmaMar, Regeneron Pharmaceuticals, Roche, and Tesaro; personal fees for participation on an Advisory Board from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, EMD Serono, Genmab, GlaxoSmithKline, ImmunoGen, Itheos, Merck Sharpe & Dohme, Mersana Therapeutics, Novocure, OneXerna Therapeutics, PharmaMar, Regeneron, Roche, Sattucklabs, Seagen, and Sutro Biopharm. S. Goksu reports institutional payment or honoraria from Bristol-Myers Squibb, Merck Sharpe & Dohme, Novartis, and Pfizer; participation on a Data Safety Monitoring Board or Advisory Board from Novartis and Pfizer. S. Roselló-Keränen reports personal payment or honoraria for presentations from Amgen, Merck Sharpe & Dohme, and Servier; personal fees for participation on an Advisory Board from Pierre Fabre and Sirtex. R. Dziadziuszko reports personal consulting fees from AstraZeneca, Bristol-Myers Squibb, Merck Sharpe & Dohme, Pfizer, Novartis, Roche, and Takeda; payment or honoraria from AstraZeneca, Amgen, Pfizer, Novartis, Roche, and Takeda; support for attending meetings and or travel from Pfizer; receipt of equipment, materials, drugs, medical writing, gifts, or other services from Novartis and Pfizer. C. Habigt is a Roche employee with stock options. D. Marbach is a Roche employee. C. Boetsch is a Roche employee with stock options. D. Dejardin is a Roche employee with patents/stocks. N. Sleiman is a Roche employee. S. Evers is a former Roche employee and current shareholder. M. Richard is a Roche employee with stock options. C. Ardeshir is a Roche employee and shareholder. J. Charo is a Roche employee with patents/stocks. A. Kraxner is a Roche employee with stocks and stock options. V. Teichgräber is a Roche employee with stock options. N. Keshelava is a Roche employee with stock options. A. Italiano, D. Tosi, V. Moiseyenko, M. Gumus, C. Arslan, C. Lindsay, S. Deva, S. Rottey, I. Cicin, and A. Smolin have no disclosures to report., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ramp lesions (RLs) are peripheral lesions that occur in the posterior part of the medial meniscus or where it attaches to the joint capsule. The classification of the medial meniscus RLs has been the focus of numerous studies and publications. This review provides an overview of RL's current classification and treatment options in anterior cruciate ligament deficient knees. The study also aims to present a more practical classification system for RLs to assist in treatment decision-making. For the first time, we also presented a new surgical treatment for incomplete inferior and double-complete RL based on the posterior knee arthroscopy that provides direct access to the posterior meniscal borders, enabling effective treatment and stronger biomechanical repair., Level of Evidence: Level V., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Freshwater jellyfish (= limnic medusa-budding hydrozoans, FWJ) are a small group of cnidarians found on all continents except Antarctica in temperate to tropical latitudes. Members of this group belong primarily to three genera: Astrohydra , Craspedacusta , and Limnocnida . While Astrohydra and Limnocnida are typically restricted to the islands of Japan, Africa, and the Indian subcontinent, one species or potential species complex, Craspedacusta sowerbii , became globally invasive. Despite research going back about one-and-a-half centuries, little is known about their phylogeny and ecology compared to marine jellyfish. Recent species distribution modelling, however, showed that by 2050, C. sowerbii will potentially extend their distribution ranges due to global warming to high-latitude ecosystems and be present (medusa stage) for an extended time in the seasonal limnic production cycle. An increase in their relative ecological importance with temporal and spatial spreading is hypothesised. Only recently, it has been shown that the trophic roles of polyps and medusae and their prey overlap with other ecosystem members. In addition, medusa behaviour may cause trophic cascades and alter vertical nutrient distributions. However, polyps and other benthic life cycle stages are understudied. In globally, changing freshwater ecosystems that may become more accommodating for FWJ, an improved understanding of their population biology and ecosystem ecology is urgently needed. In this integrative review, we, therefore, explore reasons for the hampered historical research progress, contrast developments with those of marine cnidarians, compile and publish alongside an extensive and unprecedented literature database, and formulate avenues for future directions in FWJ research., Competing Interests: The authors declare that there is no conflict of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: Janus kinase (JAK) inhibition is a promising approach for treating vitiligo. We aimed to assess the efficacy and safety of upadacitinib, an oral selective JAK inhibitor, in adults with non-segmental vitiligo., Methods: This was a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study completed at 33 clinical centres in the United States, Canada, France, and Japan. Eligible patients were aged 18-65 years with non-segmental vitiligo and had a Facial Vitiligo Area Scoring Index (F-VASI) ≥0.5 and a Total Vitiligo Area Scoring Index (T-VASI) ≥5. Patients were randomly assigned (2:2:2:1:1) using an interactive response technology to receive upadacitinib 6 mg (UPA6), upadacitinib 11 mg (UPA11), upadacitinib 22 mg (UPA22), or placebo (PBO; preassigned to switch to either UPA11 or UPA22 in period 2) once daily for 24 weeks (period 1). For weeks 24-52 (period 2), patients randomly assigned to upadacitinib continued their treatment, and patients receiving PBO switched to their preassigned upadacitinib dose in a blinded fashion. The primary endpoint was the percent change from baseline in F-VASI at week 24. Efficacy was analysed in the intention-to-treat population, and safety was examined in all randomly assigned patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT04927975., Findings: Between June 16, 2021, and June 27, 2022, 185 patients (including 115 [62%] who were female and 70 [38%] who were male) were randomly assigned to UPA6 (n = 49), UPA11 (n = 47), UPA22 (n = 43), or PBO (n = 46). At week 24, the LS mean difference versus PBO in the percent change from baseline in F-VASI was -7.60 (95% CI -22.18 to 6.97; p = 0.3037) for UPA6, -21.27 (95% CI -36.02 to -6.52; p = 0.0051) for UPA11, and -19.60 (95% CI -35.04 to -4.16; p = 0.0132) for UPA22. The LS mean difference versus PBO in the percent change from baseline in T-VASI was -7.45 (95% CI -16.86 to 1.96; p = 0.1198) for UPA6, -10.84 (95% CI -20.37 to -1.32; p = 0.0259) for UPA11 and -14.27 (95% CI -24.24 to -4.30; p = 0.0053) for UPA22. Ongoing treatment with upadacitinib induced continuous skin repigmentation over time without reaching a plateau through week 52. The rates for study drug discontinuation and serious treatment-emergent adverse events (TEAEs) were higher in the UPA22 group than in the UPA11 and UPA6 groups. Eight serious TEAEs, including one death of unknown cause and one case of infiltrating lobular breast carcinoma, were reported through 52 weeks; only two serious TEAEs (coronary artery arteriosclerosis [UPA6 (n = 1)] and non-fatal ischemic stroke [UPA11 (n = 1)]) were deemed by the investigator to have a reasonable possibility of being related to study drug. The one case of breast cancer in the UPA11 group was deemed unrelated to study drug, and the one death of unknown cause in the UPA22 group was reviewed and adjudicated and was deemed to be unrelated to study drug. The most common TEAEs were COVID-19, headache, acne, and fatigue. No new safety signals were observed., Interpretation: Upadacitinib monotherapy led to substantial repigmentation of both facial and total body vitiligo lesions and may offer an effective treatment option for adults with extensive non-segmental vitiligo. Based on these findings, upadacitinib 15 mg is being investigated in adults and adolescents with non-segmental vitiligo in an ongoing phase 3 randomised controlled trial., Funding: AbbVie Inc., Competing Interests: TP is a consultant for AbbVie, Almirall, Amgen, Bristol Myers Squibb, Calypso, Galderma, Incyte Corporation, Janssen, Eli Lilly, Novartis, Pfizer, Roivant, UCB, and VYNE Therapeutics. He has received grants and/or honoraria from AbbVie, ACM Pharma, Almirall, Amgen, Astellas, Bristol Myers Squibb, Calypso, Celgene, Galderma, Genzyme/Sanofi, GlaxoSmithKline, Incyte Corporation, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, Roivant, Sun Pharmaceuticals, UCB, and VYNE Therapeutics. He is the cofounder of YUKIN Therapeutics; and has patents on WNT agonists or GSK3b antagonist for repigmentation of vitiligo and the use of CXCR3B blockers in vitiligo. KE is a consultant for AbbVie, Incyte Corporation, La Roche-Posay, Pfizer, Pierre Fabre, Sanofi, and Viela Bio. IH is a consultant for AbbVie, Almirall, Avita, Boehringer Ingelheim, Galderma, Incyte, Jansen, Novartis, Pfizer, Sonoma, UCB, and Union Therapeutics. He is an investigator for Avita, Incyte, Lenicura, L’Oréal/Laroche Posay, and Pfizer, and a board member and past president of the Hidradenitis Suppurativa Foundation and Global Vitiligo Foundation. NvG is a consultant and/or investigator for AbbVie, Pfizer, Incyte, MDS/Merck, and Sunpharma and has received grants from AbbVie, Incyte, Pfizer, and COURD-COUSIN Collaboration (C3). She is the chair of the Vitiligo International Task Force group. DR has served as a consultant, spoken for, or conducted trials for the following companies: AbbVie, Abcuro, AltruBio, Amgen, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Concert, CSL Behring, Dermavant, Dermira, Galderma, Incyte, Janssen, Kyowa Kirin, Lilly, Merck, Nektar, Novartis, Pfizer, RAPT, Regeneron, Recludix, Revolo Biotherapeutics, Sanofi, Sun Pharmaceuticals, UCB, Viela Bio, and Zura Bio. JEH is a consultant for AbbVie, Aldena, Almiral, Avita, Biologics MD, Genzyme/Sanofi, Granular Therapeutics, Incyte, Klirna, LEO Pharma, Matchpoint Therapeutics, Merck, NIRA Biosciences, Pfizer, Sun Pharmaceuticals, Temprian Therapeutics, Vimela Therapeutics, and Vividion Therapeutics. He is an investigator for Genzyme/Sanofi, Incyte, LEO Pharma, Pfizer, and Sun Pharmaceuticals; and holds equity stock (founder) in Aldena, Klirna, NIRA Biosciences, and Vimela Therapeutics. AGP is a consultant for AbbVie, Arcutis, Avita, Immune Tolerance Network, Incyte, Pfizer, Thalocan, WCG/Trifecta, Twi Pharmaceuticals, Villaris, Vimela, and VYNE Therapeutics. He is an investigator for Incyte; and holds stock options in Tara Medical and Zerigo Health. BJS, XW, XH, AMS, and HSC are full-time employees of AbbVie and may own stock and/or options and patents., (© 2024 The Author(s).)

In the tropics, more precisely in equatorial dense rainforest, xylogenesis is driven by a little distinct climatological seasonality, and many tropical trees do not show clear growth rings. This makes retrospective analyses and modeling of future tree performance difficult. This research investigates the presence, the distinctness, and the periodicity of growth ring for dominant tree species in two semi-deciduous rainforests, which contrast in terms of precipitation dynamics. Eighteen tree species common to both forests were investigated. We used the cambial marking technique and then verified the presence and periodicity of growth-ring boundaries in the wood produced between pinning and collection by microscopic and macroscopic observation. The study showed that all eighteen species can form visible growth rings in both sites. However, the periodicity of ring formation varied significantly within and between species, and within sites. Trees from the site with clearly defined dry season had a higher likelihood to form periodical growth rings compared to those from the site where rainfall seasonality is less pronounced. The distinctness of the formed rings however did not show a site dependency. Periodical growth-ring formation was more likely in fast-growing trees. Furthermore, improvements can be made by a detailed study of the cambial activity through microcores taken at high temporal resolution, to get insight on the phenology of the lateral meristem., Competing Interests: The authors declare that the research was conducted in the absence of any conflict of interest., (© 2024 The Author(s). Plant‐Environment Interactions published by New Phytologist Foundation and John Wiley & Sons Ltd.)

The breakdown of plant material fuels soil functioning and biodiversity. Currently, process understanding of global decomposition patterns and the drivers of such patterns are hampered by the lack of coherent large-scale datasets. We buried 36,000 individual litterbags (tea bags) worldwide and found an overall negative correlation between initial mass-loss rates and stabilization factors of plant-derived carbon, using the Tea Bag Index (TBI). The stabilization factor quantifies the degree to which easy-to-degrade components accumulate during early-stage decomposition (e.g. by environmental limitations). However, agriculture and an interaction between moisture and temperature led to a decoupling between initial mass-loss rates and stabilization, notably in colder locations. Using TBI improved mass-loss estimates of natural litter compared to models that ignored stabilization. Ignoring the transformation of dead plant material to more recalcitrant substances during early-stage decomposition, and the environmental control of this transformation, could overestimate carbon losses during early decomposition in carbon cycle models., (© 2024 The Authors. Ecology Letters published by John Wiley & Sons Ltd.)

Batrachochytrium dendrobatidis (Bd) is a lethal fungal species that parasitizes vertebrates and is associated with the worldwide decline of amphibian populations. The development of sensitive, rapid detection methods, particularly DNA-based techniques, is critical for effective management strategies. This study evaluates the efficacy of DNA extraction and a portable PCR device in a mountable field laboratory setup for detecting Bd near the habitats of three critically endangered Atelopus toad species in Ecuador. We collected skin swabs from Atelopus balios, A. nanay, and A. bomolochos, and environmental DNA (eDNA) samples from streams in Andean and coastal regions of Ecuador. For eDNA, a comparison was made with duplicates of the samples that were processed in the field and in a standard university laboratory. Our findings revealed Bd detection in eDNA and swabs from 6 of 12 water samples and 10 of 12 amphibian swab samples. The eDNA results obtained in the field laboratory were concordant with those obtained under campus laboratory conditions. These findings highlight the potential of field DNA-based monitoring techniques for detecting Bd in amphibian populations and their aquatic habitats, particularly in remote areas. Furthermore, this research aligns with the National Action Plan for the Conservation of Ecuadorian Amphibians and contributes to the global effort to control this invasive and deadly fungus., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Riascos-Flores et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The sinoatrial node (SAN), the primary pacemaker of the heart, is responsible for the initiation and robust regulation of sinus rhythm. 3D mapping studies of the ex-vivo human heart suggested that the robust regulation of sinus rhythm relies on specialized fibrotically-insulated pacemaker compartments (head, center and tail) with heterogeneous expressions of key ion channels and receptors. They also revealed up to five sinoatrial conduction pathways (SACPs), which electrically connect the SAN with neighboring right atrium (RA). To elucidate the role of these structural-molecular factors in the functional robustness of human SAN, we developed comprehensive biophysical computer models of the SAN based on 3D structural, functional and molecular mapping of ex-vivo human hearts. Our key finding is that the electrical insulation of the SAN except SACPs, the heterogeneous expression of If, INa currents and adenosine A1 receptors (A1R) across SAN pacemaker-conduction compartments are required to experimentally reproduce observed SAN activation patterns and important phenomena such as shifts of the leading pacemaker and preferential SACP. In particular, we found that the insulating border between the SAN and RA, is required for robust SAN function and protection from SAN arrest during adenosine challenge. The heterogeneity in the expression of A1R within the human SAN compartments underlies the direction of pacemaker shift and preferential SACPs in the presence of adenosine. Alterations of INa current and fibrotic remodelling in SACPs can significantly modulate SAN conduction and shift the preferential SACP/exit from SAN. Finally, we show that disease-induced fibrotic remodeling, INa suppression or increased adenosine make the human SAN vulnerable to pacing-induced exit blocks and reentrant arrhythmia. In summary, our computer model recapitulates the structural and functional features of the human SAN and can be a valuable tool for investigating mechanisms of SAN automaticity and conduction as well as SAN arrhythmia mechanisms under different pathophysiological conditions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

High-elevation tropical streams are under increasing threat from human activities and climate change. Specifically, Ecuadorian Andean streams require priority actions such as bioassessment (e.g., biodiversity and functional ecology of macroinvertebrates) in order to generate adequate environmental management policies. Therefore, we investigated the distribution and composition of the macroinvertebrate taxa and their functional feeding groups in relation to the environmental variables in the Antisana river basin (Andean-Ecuadorian Region). We sampled macroinvertebrates from 15 locations to assess ecological conditions (ECs), expressed as the Biological Monitoring Working Party Colombia (BMWP-Col) classes, the Andean Biotic Index (ABI) and the Andean-Amazon Biotic Index (AAMBI). Results indicate that dissolved oxygen saturation, elevation, nutrient concentration and conductivity contributed significantly to the composition of the taxa and functional feeding groups (FFGs). Taxa diversity and FFGs were more abundant in the best EC sites. Shredders (SH) were, overall, dominant and abundant at sites with medium-high ECs. Scrapers constituted the second most prevalent assemblage, exerting dominance at moderate ecological conditions (high altitude and high oxygen saturation). Collector-gathers (CGs) are less sensitive to contamination than the previous two groups but were equally abundant at medium-high EC sites. Collector-filterers (CFs) and parasites (PAs) were less abundant, although the presence of the former was slightly related to better environmental conditions. Predators (PRs) were almost absent throughout the study, but they were collected from poor EC sites. CGs, PAs and PRs showed more tolerance to the presence of human disturbances (e.g., hydraulic constructions or slope erosion). The BMWP-Col index seems to be the best fit for this ecosystem, showing a significant difference in FFG between the index classes, compared to the other indices evaluated. The results of this investigation may be regarded as a fundamental starting point and used in future bioassessment work in other similar ecosystems, particularly high-altitude tropical Ecuadorian streams.

The fitness of an organism is often impacted by the composition and biological activity of its associated bacterial community. Many factors, including host genetics, diet, and temperature can influence the bacterial community composition. Furthermore, these factors can differ strongly between natural and laboratory environments. Consequently, several studies have highlighted results from laboratory experiments investigating host-associated bacterial communities to be conflicting with those obtained under field conditions. Here, we compared the Daphnia magna gut bacterial communities in natural host populations with those of laboratory cultured hosts. We further analyzed changes in the gut bacterial communities after transferring hosts from natural populations to the laboratory on the short- and long-term. Results show that, in general, the gut bacterial communities from natural populations differ from those of laboratory cultures and that their composition and diversity changed one hour after being transferred to the laboratory. Over the following 14 days, the composition and diversity changed gradually. On the longer term (after two years of rearing hosts in the laboratory) the composition and diversity of the gut bacterial communities was strongly altered compared to the initial state. Our findings indicate that the gut bacterial communities of Daphnia magna in laboratory experiments is not representative for natural field conditions, and that caution should be taken when interpreting results from laboratory experiments for natural settings., (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.)

It is challenging to collect robust, long-term datasets to properly monitor the viability and social structure of large, long-lived animals, especially marine mammals. The present study used a unique long-term dataset to investigate the population parameters and social structure of a poorly studied population of bottlenose dolphins (Tursiops sp.) in southern Port Phillip Bay, south-eastern Australia. Photo-identification images have been collected between 2012-2022 both opportunistically and following a protocol by patrons, staff, and volunteers of ecotourism companies using their vessels as platforms. The resulting large dataset was available to be processed through the online platform Flukebook and used in capture recapture models to estimate abundance and demographic parameters. In addition, the social structure of the population and the reproductive parameters were investigated. The marked adult population abundance (45.2 ± 2.7 individuals) was found to be stable over the last decade and the calving rate ranged between 0.06-0.19 new calves per identified individuals per year, while the inter-birth interval was 3.7 ± 0.8 years. Social analysis suggested the population has a fission-fusion structure with no apparent clusters. The stability of the population over the study period suggests no deleterious effect of anthropogenic or environmental factors during the last decade. This study is the outcome of the effort of the ecotourism organisations and the results obtained, along with their similarity to those of other dolphin populations worldwide, highlight the importance of such data sources for long-term information that would otherwise be too expensive or logistically difficult to obtain., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lacetera et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Although we have sent humans into space for more than 50 years, crucial questions regarding immune response in space conditions remain unanswered. There are many complex interactions between the immune system and other physiological systems in the human body. This makes it difficult to study the combined long-term effects of space stressors such as radiation and microgravity. In particular, exposure to microgravity and cosmic radiation may produce changes in the performance of the immune system at the cellular and molecular levels and in the major physiological systems of the body. Consequently, abnormal immune responses induced in the space environment may have serious health consequences, especially in future long-term space missions. In particular, radiation-induced immune effects pose significant health challenges for long-duration space exploration missions with potential risks to reduce the organism's ability to respond to injuries, infections, and vaccines, and predispose astronauts to the onset of chronic diseases (e.g., immunosuppression, cardiovascular and metabolic diseases, gut dysbiosis). Other deleterious effects encountered by radiation may include cancer and premature aging, induced by dysregulated redox and metabolic processes, microbiota, immune cell function, endotoxin, and pro-inflammatory signal production 1,2 . In this review, we summarize and highlight the current understanding of the effects of microgravity and radiation on the immune system and discuss knowledge gaps that future studies should address., (© 2023. The Author(s).)

Background: Globally, cervical cancer is a major public health problem, with about 604,000 new cases and over 340,000 deaths in 2020. In Kenya, it is the leading cause of cancer deaths, with over 3,000 women dying in 2020 alone. Both the Kenyan cancer screening guidelines and the World Health Organization's Global Cervical Cancer Elimination Strategy recommend human papillomavirus (HPV) testing as the primary screening test. However, HPV testing is not widely available in the public healthcare system in Kenya. We conducted a pilot study using a point of care (POC) HPV test to inform national roll-out., Methods: The pilot was implemented from October 2019 to December 2020, in nine health facilities across six counties. We utilized the GeneXpert platform (Cepheid, Sunnyvale, CA, USA), currently used for TB, Viral load testing and early infant diagnosis for HIV, for HPV screening. Visual inspection with acetic acid (VIA) was used for triage of HPV-positive women, as recommended in national guidelines. Quality assurance (QA) was performed by the National Oncology Reference Laboratory (NORL), using the COBAS 4800 platform (Roche Molecular System, Pleasanton, CF, USA). HPV testing was done using either self or clinician-collected samples. We assessed the following screening performance indicators: screening coverage, screen test positivity, triage compliance, triage positivity and treatment compliance. Test agreement between local GeneXpert and central comparator high-risk HPV (hrHPV) testing for a random set of specimens was calculated as overall concordance and kappa value. We conducted a final evaluation and applied the Nominal Group Technique (NGT) to identify implementation challenges and opportunities., Key Findings: The screening coverage of target population was 27.0% (4500/16,666); 52.8% (2376/4500) were between 30-49 years of age. HPV positivity rate was 22.8% (1027/4500). Only 10% (105/1027) of HPV positive cases were triaged with VIA/VILI; 21% (22/105) tested VIA/VILI positive, and 73% (16/22) received treatment (15 received cryotherapy, 1 was referred for biopsy). The median HPV testing turnaround time (TAT) was 24 hours (IQR 2-48 hours). Invalid sample rate was 2.0% (91/4500). Concordance between the Cepheid and COBAS was 86.2% (kappa value = 0.71). Of 1042 healthcare workers, only 5.6% (58/1042) were trained in cervical cancer screening and treatment, and only 69% (40/58) of those trained were stationed at service provision areas. Testing capacity was identifed as the main challenge, while the community strategy was the main opportunity., Conclusion: HPV testing can be performed on GeneXpert as a near point of care platform. However, triage compliance and testing TAT were major concerns. We recommend strengthening of the screening-triage-treatment cascade and expansion of testing capacity, before adoption of a GeneXpert-based HPV screening among other near point of care platforms in Kenya., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mwenda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Aims: We aimed to identify mucin-microbiome signatures shaping the tumor microenvironment in gastric adenocarcinomas and clinical outcomes., Methods: We performed high-throughput profiling of the mucin phenotypes present in 108 gastric adenocarcinomas and 20 functional dyspepsia cases using validated mucin-based RT-qPCRs with subsequent immunohistochemistry validation and correlated the data with clinical outcome parameters. The gastric microbiota was assessed by 16S rRNA gene sequencing, taxonomy, and community composition determined, microbial networks analyzed, and the metagenome inferred in association with mucin phenotypes and expression., Results: Gastric adenocarcinomas with an intestinal mucin environment or high-level MUC13 expression are associated with poor survival. On the contrary, gastric MUC5AC or MUC6 abundance was associated with a more favorable outcome. The oral taxa Neisseria, Prevotella, and Veillonella had centralities in tumors with intestinal and mixed phenotypes and were associated with MUC13 overexpression, highlighting their role as potential drivers in MUC13 signaling in GC. Furthermore, dense bacterial networks were observed in intestinal and mixed mucin phenotype tumors whereas the lowest community complexity was shown in null mucin phenotype tumors due to higher Helicobacter abundance resulting in a more decreased diversity. Enrichment of oral or intestinal microbes was mucin phenotype dependent. More specifically, intestinal mucin phenotype tumors favored the establishment of pro-inflammatory oral taxa forming strong co-occurrence networks., Conclusions: Our results emphasize key roles for mucins in gastric cancer prognosis and shaping microbial networks in the tumor microenvironment. Specifically, the enriched oral taxa associated with aberrant MUC13 expression can be potential biomarkers in predicting disease outcomes. Video Abstract., (© 2023. The Author(s).)

Background: There is a growing number of patients with ventricular paced rhythm, who present to the emergency department with chest pain. The diagnosis of ST-segment elevation myocardial infarction (STEMI) and subsequent percutaneous coronary intervention (PCI) is often postponed, as the 12 leads-electrocardiogram (ECG) is discarded as not interpretable. There is a growing body of literature that suggests that Smith-modified Sgarbossa criteria can be applied for the diagnosis of STEMI in patients with paced rhythms. These criteria were originally developed for the interpretation of ECGs in patients with a left bundle branch block (LBBB) and chest pain, but have been expanded to paced ECGs., Methodology: We present three case reports with chest pain and right ventricular or biventricular pacing., Findings: In all three cases, the Smith-modified Sgarbossa was positive and the diagnosis of STEMI could have been made early on., Implications: It remains important to look for ST-segment deviations and to compare the symptomatic ECG with previous asymptomatic ECGs. As the number of patients with potential acute myocardial infarction (AMI) and paced rhythms is likely to rise in the future, these criteria should be known to emergency physicians and cardiologists.

Introduction: Obesity is associated with a number of chronic diseases such as cardiovascular diseases and cancers. The association of obesity with occupational accidents has been suggested although the evidence is less convincing. The objective of the study is to analyse the relationship between BMI values and ergonomic accidents in a large University Hospital., Methods: The relationship between body mass index (BMI) and the incidence of ergonomic occupational accidents over a period of 8 years was investigated in a cohort of employees of a large University Hospital, covering almost 27,000 person-years of observation. This relationship was stratified according to the variables age, gender, functional status within the organization and work schedule (part-time or full time). Height and weight were objectively measured, demographic data were obtained from the human resource department and the registration of ergonomic accidents was carried out by the safety and prevention department of the hospital., Results: The number of ergonomic accidents, expressed as number/1000 person-years was higher for female employees compared to male employees, increased with age and markedly increased from functional class A (leading or expert function and higher educational level) to D (executive function in patient care and technical department). However, the incidence of ergonomic accidents accompanied by loss of working time was not significantly associated with BMI, independently of age and gender. In addition, the type of accident and the severity of the accidents expressed as the number of days absent from work were unrelated to BMI., Conclusion: No independent relationship between BMI and the incidence of ergonomic accidents could be identified in our cohort. Tailoring working conditions to individual BMI levels is not recommended.

The thymus is a lymphatic mediastinal organ that is largely subject to changes with age. In human patients, the CT characteristics of the thymus in children and adults is well described. Furthermore, it is known in human medicine that stress can lead to a reduction in the size of the thymus, followed by a phase of hyperplasia (called the 'rebound effect'). The visualization of thymic tissue in the cranial mediastinum of adult dogs with neoplasia is possible and could be related to a similar effect. In this study, we aimed to describe the CT characteristics of the thymus in adult dogs with neoplasia and to compare the aspect of the thymus in these dogs to juvenile dogs with a presumed normal thymus. A total of 11 adult dogs with neoplasia and 20 juvenile dogs were included. Several CT features of the thymus were evaluated, including the size, shape, and pre- and post-contrast attenuation values. The overall appearance was lobulated in all of the adult dogs and homogeneous in all of the juvenile dogs; it was left-sided in all of the adult dogs, while it was located in the midline in a few of the juvenile dogs (right-sided only in one). The thymus was less attenuating in adult dogs, in some cases with negative minimum pre-contrast attenuation values. In some dogs with neoplasia, the thymus can be detected at CT examination despite their age.

Background: There is a lack of knowledge about the ways physiotherapists around the world learn about professional code of ethics and ethical decision-making frameworks. The profession has a gap in the understanding about physiotherapists' views on factors that play a role in ethical decision-making and whether these views differ between World Physiotherapy regions., Methods: An online survey study in English was conducted from October 2018 to October 2019. Participants included 559 physiotherapists located in 72 countries. The self-designed survey questionnaire contained 13 items asking about demographic information and means of learning about ethical codes and decision-making frameworks. A further 30 items were presented which included statements underpinned with individual, organisational, situational and societal factors influencing ethical decision-making. Participants were asked to express their level of agreement or disagreement using a 5-point-Likert-scale., Results: Participants' highest rated responses endorsed that the professional role of physiotherapists is linked to social expectations of ethical behaviour and that ethical decision-making requires more skills than simply following a code of ethics. A recognisable organisational ethical culture was rated as supporting good ethical decisions. Comparing responses by World Physiotherapy regions showed significant differences in factors such as culture, religion, emotions, organisational values, significant others, consequences of professional misconduct and professional obligations. Entry level education was not perceived to provide a solid base for ethical decision-making in every World Physiotherapy region. Participants reported multiple sources for learning about a professional code of ethics and ethical decision-making frameworks. What's more, the number of sources differed between World Physiotherapy regions., Conclusions: Multiple factors play a role in physiotherapists' ethical decision-making internationally. Physiotherapists' ethical knowledge is informed by, and acquired from, several learning sources, which differ in both quality and quantity amongst World Physiotherapy regions. Easily accessible knowledge and education about professional codes of ethics and ethical decision-making can foster continuing professional development for physiotherapists. The establishment of constructive ethical cultures in workplaces can improve ethical decision-making, and should acknowledge the influence of individual, organisational, situational and societal factors. The establishment of collaborative learning environments can support knowledge translation which acknowledges practice-based methods of knowing and learning., (© 2023. The Author(s).)

Aims: For patients with cartilage defects of the knee, a new biocompatible and in situ cross-linkable albumin-hyaluronan-based hydrogel has been developed for matrix-associated autologous chondrocyte implantation (M-ACI) - NOVOCART Inject plus (Ninject; TETEC AG, Reutlingen, Germany). We aimed to estimate the potential cost-effectiveness of NInject, that is not available on the market, yet compared to spheroids of human autologous matrix-associated chondrocytes (Spherox; CO.DON GmbH, Leipzig, Germany) and microfracture., Materials and Methods: An early Markov model was developed to estimate the cost-effectiveness in the United Kingdom (UK) from the payer perspective. Transition probabilities, response rates, utility values and costs were derived from literature. Since NInject has not yet been launched and no prices are available, its costs were assumed equal to those of Spherox. Cycle length was set at one year and the time horizon chosen was notional patients' remaining lifetime. Model robustness was evaluated with deterministic and probabilistic sensitivity analyses (DSA; PSA) and value of information analysis (VOIA). The Markov model was built using TreeAge Pro Healthcare., Results: NInject was cost-effective compared to microfracture (ICER: ₤5,147) while Spherox was extendedly dominated. In sensitivity analyses, the ICER exceeded conventional WTP threshold of ₤20,000 only when the utility value after successful first treatment with NInject was decreased by 20% (ICER: ₤69,620). PSA corroborated the cost-effectiveness findings of NInject, compared to both alternatives, with probabilities of 60% of NInject undercutting the aforementioned WTP threshold and being the most cost-effective alternative. The VOIA revealed that obtaining additional evidence on the new technology will likely not be cost-effective for the UK National Health Service., Limitations and Conclusion: This early Markov model showed that NInject is cost-effective for the treatment of articular cartilage defects in the knee, compared to Spherox and microfracture. However, as the final price of NInject has yet to be determined, the cost-effectiveness analysis performed in this study is provisional, assuming equal prices for NInject and Spherox.

Haemal lordosis, a frequent skeletal deformity in teleost fish, has long been correlated with increased mechanical loads induced by swimming activity. In the present study, we examine whether juvenile zebrafish can recover from haemal lordosis and explore the musculoskeletal mechanisms involved. Juveniles were subjected to a swimming challenge test (SCT) that induced severe haemal lordosis in 49% of the animals and then immediately transferred them to 0.0 total body lengths (TL) per second of water velocity for a week. The recovery from lordosis was examined by means of whole mount staining, histology and gene expression analysis. Results demonstrate that 80% of the lordotic zebrafish are capable of internal and external recovery within a week after the SCT. Recovered individuals presented normal shape of the vertebral centra, maintaining though distorted internal tissue organization. Through the transcriptomic analysis of the affected haemal regions, several processes related to chromosome organization, DNA replication, circadian clock and transcription regulation were enriched within genes significantly regulated behind this musculoskeletal recovery procedure. Genes especially involved in adipogenesis, bone remodeling and muscular regeneration were regulated. A remodeling tissue-repair hypothesis behind haemal lordosis recovery is raised. Limitations and future possibilities for zebrafish as a model organism to clarify mechanically driven musculoskeletal changes are discussed., (© 2022. The Author(s).)

Introduction: Health-care organizations are facing a high burden of ergonomic occupational accidents, and prevention is a continuous point of interest. In this manuscript, we describe the characteristics of ergonomic accidents in a large Belgian university hospital and discuss the value of near misses., Methods: Combining databases, we identified the frequency [number of accidents × 10 6 hours worked per year], severity (number of days off work × 10 3 hours worked per year), and profile of the victims of occupational ergonomic accidents (with absence from work) or incidents or near-misses (without absence from work). Ergonomic accidents and incidents include slips, trips, falls, injurious body movements, overexertion, and handling heavy weights., Results: In a period of 23 years, we noticed a significant decrease in the frequency of ergonomic accidents (from about 7 to about 4 standard units), without changes in the severity. The decrease in the frequency of accidents is mirrored by an increase in the frequency of incidents (from about 4 to about 6 standard units). Female and older employees are more vulnerable to accidents, and the frequency was between two and four times higher for employees mostly involved in manual tasks compared to employees mostly involved in managerial tasks. The profile of the victims and the causes of accidents and incidents were identical., Conclusion: Although it is premature to assume a cause-consequence relationship between incidents and accidents, it is tempting to speculate that the increased ratio of the frequencies of incidents over accidents might be one of the variables reflecting the adequacy of preventive measures and the growth of safety behavior.

Background: A clear patency benefit of a drug-eluting stent (DES) over bare metal stents (BMSs) for treating peripheral artery disease of the femoropopliteal segment has not been definitively demonstrated. The EMINENT study (Trial Comparing Eluvia Versus Bare Metal Stent in Treatment of Superficial Femoral and/or Proximal Popliteal Artery) was designed to evaluate the patency of the Eluvia DES (Boston Scientific, Marlborough, MA), a polymer-coated paclitaxel-eluting stent, compared with BMSs for the treatment of femoropopliteal artery lesions., Methods: EMINENT is a prospective, randomized, controlled, multicenter European study with blinded participants and outcome assessment. Patients with symptomatic peripheral artery disease (Rutherford category 2, 3, or 4) of the native superficial femoral artery or proximal popliteal artery with stenosis ≥70%, vessel diameter of 4 to 6 mm, and total lesion length of 30 to 210 mm were randomly assigned 2:1 to treatment with DES or BMS. The primary effectiveness outcome was primary patency at 12 months, defined as independent core laboratory-assessed duplex ultrasound peak systolic velocity ratio ≤2.4 in the absence of clinically driven target lesion revascularization or surgical bypass of the target lesion. Primary sustained clinical improvement was a secondary outcome defined as a decrease in Rutherford classification of ≥1 categories compared with baseline without a repeat target lesion revascularization. Health-related quality of life and walking function were assessed., Results: A total of 775 patients were randomly assigned to treatment with DES (n=508) or commercially available BMSs (n=267). Baseline clinical, demographic, and lesion characteristics were similar between the study groups. Mean lesion length was 75.6±50.3 and 72.2±47.0 mm in the DES and BMS groups, respectively. The 12-month incidence of primary patency for DES treatment (83.2% [337 of 405]) was significantly greater than for BMS (74.3% [165 of 222]; P <0.01). Incidence of primary sustained clinical improvement was greater among patients treated with the DES than among those who received a BMS (83.0% versus 76.6%; P =0.045). The health-related quality of life dimensions of mobility and pain/discomfort improved for the majority of patients in both groups (for 66.4% and 53.6% of DES-treated and for 64.2% and 58.1% of BMS-treated patients, respectively) but did not differ significantly. At 12 months, no statistical difference was observed in all-cause mortality between patients treated with the DES or BMS (2.7% [13 of 474] versus 1.1% [3 of 263]; relative risk, 2.4 [95% CI, 0.69-8.36]; P =0.15)., Conclusions: By demonstrating superior 1-year primary patency, the results of the EMINENT randomized study support the benefit of using a polymer-based paclitaxel-eluting stent as a first-line stent-based intervention for patients with symptomatic peripheral artery disease attributable to femoropopliteal lesions., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02921230.

We report detailed functional analyses and genotype-phenotype correlations in 392 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel Nav1.6, with the aim of describing clinical phenotypes related to functional effects. Six different clinical subgroups were identified: Group 1, benign familial infantile epilepsy (n = 15, normal cognition, treatable seizures); Group 2, intermediate epilepsy (n = 33, mild intellectual disability, partially pharmaco-responsive); Group 3, developmental and epileptic encephalopathy (n = 177, severe intellectual disability, majority pharmaco-resistant); Group 4, generalized epilepsy (n = 20, mild to moderate intellectual disability, frequently with absence seizures); Group 5, unclassifiable epilepsy (n = 127); and Group 6, neurodevelopmental disorder without epilepsy (n = 20, mild to moderate intellectual disability). Those in Groups 1-3 presented with focal or multifocal seizures (median age of onset: 4 months) and focal epileptiform discharges, whereas the onset of seizures in patients with generalized epilepsy was later (median: 42 months) with generalized epileptiform discharges. We performed functional studies expressing missense variants in ND7/23 neuroblastoma cells and primary neuronal cultures using recombinant tetrodotoxin-insensitive human Nav1.6 channels and whole-cell patch-clamping. Two variants causing developmental and epileptic encephalopathy showed a strong gain-of-function (hyperpolarizing shift of steady-state activation, strongly increased neuronal firing rate) and one variant causing benign familial infantile epilepsy or intermediate epilepsy showed a mild gain-of-function (defective fast inactivation, less increased firing). In contrast, all three variants causing generalized epilepsy induced a loss-of-function (reduced current amplitudes, depolarizing shift of steady-state activation, reduced neuronal firing). Functional effects were known for 170 individuals. All 136 individuals carrying a functionally tested gain-of-function variant had either focal (n = 97, Groups 1-3) or unclassifiable (n = 39) epilepsy, whereas 34 individuals with a loss-of-function variant had either generalized (n = 14), no (n = 11) or unclassifiable (n = 6) epilepsy; only three had developmental and epileptic encephalopathy. Computational modelling in the gain-of-function group revealed a significant correlation between the severity of the electrophysiological and clinical phenotypes. Gain-of-function variant carriers responded significantly better to sodium channel blockers than to other anti-seizure medications, and the same applied for all individuals in Groups 1-3. In conclusion, our data reveal clear genotype-phenotype correlations between age at seizure onset, type of epilepsy and gain- or loss-of-function effects of SCN8A variants. Generalized epilepsy with absence seizures is the main epilepsy phenotype of loss-of-function variant carriers and the extent of the electrophysiological dysfunction of the gain-of-function variants is a main determinant of the severity of the clinical phenotype in focal epilepsies. Our pharmacological data indicate that sodium channel blockers present a treatment option in SCN8A-related focal epilepsy with onset in the first year of life., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This research was conducted to evaluate the replacement potential of Acacia nilotica dried leaf meal for Noug Seed Cake (NSC) to supplement low quality grass hay in the diet of crossbred sheep (25% Dorper). In doing so, four treatments were set up in such a way that 0%, 33%, 67%, and 100% NSC is replaced with dried leaf of Acacia nilotica from a conventional supplement while the treatments were kept isonitrogenous. The experiment was set up in a Randomized Complete Block Design, with initials weight used as the blocking factor. Twenty animals were allocated to the four treatments. The experiment consisted of hundred days of feeding trial followed by evaluation of carcass components at the end. In addition, the experimental feed ingredient was studied in vitro for gas production, methane (CH 4 ) production, fractional rate of degradation (Kd), and in vitro dry matter digestibility (IVDMD). In view of chemical composition, grass hay contained lower crude protein (CP = 3.2% DM) and high cell wall contents that makes it lower quality feed. On the other hand, Acacia nilotica leaf meal was moderate in quality (CP = 14.3% DM) that can support moderate level of ruminant production. In an in vitro study, Acacia nilotica was found to have lower (P < 0.01) levels of CH 4 , total gas, kd, and IVDMD compared to the other feed ingredients. This indicates that tannin have an effect on Acacia nilotica feed. Partial and complete replacement of NSC with Acacia nilotica leaf meal significantly increased total dry matter intake (TDMI) (P < 0.001). Average daily gain (ADG) and dressing percentage was also higher for leaf meal supplemented groups. Hot carcass weight was in the range of 14.8-17.8 kg, which is higher than the national average carcass weight for Ethiopian sheep, and it was also found to be higher when NSC was partially (33%) as well as completely replaced by the leaf meal. In general, NSC can be replaced either partially or completely with Acacia nilotica leaf meal in the diet of 25% Dorper crosses while weight gain as well as carcass yield is promoted. The maximum inclusion level of Acacia nilotica was 61.3% or 319.2 g per day for 25% Dorper cross sheep fed natural pasture hay as a basal diet., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)