Search Results (11,990)

Yaks are a critical livestock species for plateau regions; however, their poor reproductive efficiency—characterized by low estrus and pregnancy rates—significantly hampers genetic improvement and industry sustainability. Although synchronization protocols are widely utilized in cows to enhance reproductive performance, research on yaks is limited. Our study systematically evaluated 3 estrus synchronization protocols (CIDR-GPPG, CIDR-GPG, GPPG) on 99 female yaks. The GPPG treatment resulted in the lowest estrus detection (40.63%) and pregnancy rate (15.38%), while the CIDR-GPG protocol significantly improved these rates, achieving an estrus rate of 65.71% and a pregnancy rate of 52.17%. Notably, serum estradiol concentrations were significantly elevated in the CIDR-GPG group compared to the GPPG group. Given the importance of body condition for synchronization outcomes, we analyzed correlation between body measurements and reproductive performance. Among 10 body measurements, chest girth demonstrated the strongest positive correlation with both estrus (R = 0.75) and pregnancy success (R = 0.72). Further logistic regression modeling based on chest girth generated robust predictors for estrus (AUC = 0.934) and pregnancy (AUC = 0.923). Importantly, CIDR-GPG protocol effectively lowered the body condition threshold required for successful reproductive outcomes, indicating that yaks with smaller chest girths can still achieve comparable probabilities of estrus and pregnancy when employing this protocol. Overall, our findings supported the CIDR-GPG protocol as an effective strategy for optimizing yak reproduction and highlighted chest girth as a valuable indicator for predicting reproductive outcomes, providing a practical approach to enhance reproductive management, even in animals with suboptimal body conditions. Full article

mRNA vaccines are a relevant approach in cancer immunotherapy, using messenger RNA to induce immune responses against tumor-associated antigens. In this review, BNT111 and BNT122 are compared as representative off-the-shelf and personalized models. BNT111 is a fixed mRNA vaccine that has demonstrated significant antitumor efficacy against shared melanoma antigens, particularly when combined with immune checkpoint inhibitors. It allows a standardized production via in vitro transcription (IVT) in a cell-free system. Conversely, BNT122 is a personalized vaccine designed to match an individual’s tumor mutations by targeting patient-specific neoantigens to elicit more robust immune responses. It has significant suitability in the adjuvant setting to target minimal residual disease. Despite favorable safety and immunogenicity, the effectiveness of these vaccines is influenced by various factors, including tumor heterogeneity, differences in antigen expression, off-target effects on mRNA-LNP distribution, molecular instability, and complex manufacturing constraints. Neither approach can be directly considered as the definitive optimal vaccine. A comprehensive analysis of their strengths and limitations is vital for a balanced and objective future research direction. Collectively, this emphasizes the need for further improvements in vaccine design and strategies, prioritizing high-quality, safe, and accessible treatments for every cancer-based patient and ensuring their successful integration into healthcare. Full article

Recurrent intrauterine adhesions (IUA) and refractory thin endometrium are associated with impaired endometrial regeneration, reduced implantation, and poor live birth outcomes. Regenerative therapy using mesenchymal stromal cells (MSCs) has shown promising results; however, factors associated with reproductive success remain unclear. In this prospective, single-centre, single-arm uncontrolled observational study, 35 women with recurrent IUA and thin endometrium (<7 mm) unresponsive to standard surgical and hormonal therapy received combined subendometrial and systemic administration of placenta-derived MSCs. The primary endpoint was live birth. Secondary endpoints included clinical pregnancy rate, time to pregnancy, endometrial thickness changes, uterine blood flow (resistance index, RI), and anti-Müllerian hormone (AMH) levels. Univariable logistic regression was performed to identify factors associated with live birth. Clinical pregnancy occurred in 13/35 patients (37.1%), and live birth was achieved in 11/35 (31.4%). Median time to pregnancy was 7 (5–8) months. Shorter duration of infertility or prior pregnancy loss (OR 1.55 per year; 95% CI 1.10–2.57), AFS stage I adhesions (OR 6.8; 95% CI 1.1–42; p = 0.04), lower baseline RI in uterine, arcuate and radial arteries, and higher baseline AMH (OR 2.59 per doubling; 95% CI 1.15–6.89) were significantly associated with live birth. Endometrial thickness increased after therapy but was not significantly associated with live birth. No severe adverse events were observed. Placenta-derived MSC therapy was followed by live birth in 31.4% of women with recurrent IUA and refractory thin endometrium. A shorter duration of reproductive disorders, less severe adhesions, lower baseline RI in uterine, arcuate and radial arteries, and higher AMH levels were associated with live birth after treatment and may help identify patients with a more favourable reproductive prognosis in future controlled studies. Full article

Background/Objectives: Orofacial myofunctional therapy (OMT) is a system of targeted neuromuscular exercises and behavioral retraining intended to optimize tongue, lip, jaw, and airway function during rest, breathing, swallowing, and sleep. Historically associated with tongue thrust and abnormal swallowing, OMT is now applied across an expanding range of clinical contexts, including sleep-disordered breathing (SDB), tongue-tie rehabilitation, orthodontic stability, and perioperative functional recovery. As its use has broadened, persistent questions have followed: what is myofunctional therapy, where did it originate, and how did a set of oral exercises evolve into an intervention increasingly integrated with airway health, sleep medicine, and surgical care? Methods: This article presents a narrative historical review with a perspective component, synthesizing foundational literature, interdisciplinary contributions, and selected contemporary evidence to examine the evolution of OMT from ancient functional practices to modern clinical science. It is written to trace recurring clinical observations, shifts in educational frameworks, and key inflection points that shaped how OMT has been taught and applied over time. Results: OMT did not emerge from randomized controlled trials or standardized protocols. It arose from repeated clinical encounters with patients with atypical craniofacial development, relapse of structural correction, persistent mouth breathing, and/or unresolved swallowing and speech dysfunction despite technically successful treatment. These patterns suggested that anatomy alone could not account for outcome variability. Over time, clinical attention expanded beyond isolated tongue function to include breathing patterns, posture, neuromuscular tone, and airway behavior. In the past two decades, controlled trials, cohort studies, and systematic reviews have supported selected applications of OMT, particularly in SDB and adjunctive airway care, while also revealing ongoing challenges related to training variability, terminology, scope of practice, and standardization. Conclusions: OMT has historically been described as a system of targeted neuromuscular and behavioral interventions aimed at modifying orofacial rest posture and function. Over time, the field has expanded beyond localized muscle retraining toward a broader functional framework that integrates airway physiology, craniofacial growth, sleep, and interdisciplinary rehabilitation. Full article

Background: In zoster-associated pain (ZAP), earlier epidural steroid injection (ESI) has been associated with better outcomes, but optimal timing remains unclear, and prior studies have largely relied on pain reduction alone. Methods: In this multicenter retrospective cohort, 215 patients with ZAP who completed a three-session ESI course were classified into early (<30 days) and delayed (≥30–≤180 days) groups. The primary endpoint was complete remission at 12 weeks (≥50% visual analog scale [VAS] reduction, VAS ≤ 2, and sensory normalization); successful response (≥50% VAS reduction) served as the secondary endpoint. An ordered three-category framework and an exploratory generalized Youden index threshold analysis were applied. Results: Complete remission occurred in 82.1% versus 39.0% and successful response in 91.7% versus 67.8%. Each additional day of delay was associated with lower odds of complete remission (adjusted odds ratio [aOR], 0.957; p < 0.001) and higher odds of a worse outcome category (aOR, 1.030; p < 0.001). Exploratory candidate boundaries were 22 and 42 days. Conclusions: Earlier ESI initiation was associated with a higher likelihood of complete remission incorporating pain reduction, low residual pain intensity, and sensory normalization. These findings highlight the clinical relevance of treatment timing and recovery assessment beyond pain reduction alone in ZAP. Full article

Insufficient oxidative capacity can limit humification during municipal sludge composting. This study comparatively evaluated two Fenton-like amendment systems, a homogeneous copper-based treatment (CH) and a heterogeneous nano-iron-based treatment (NFH), for their effects on composting performance, humification-related indices, spectroscopic characteristics, and bacterial community succession. Both amended treatments improved composting performance relative to the control, reaching higher peak temperatures (68.5 °C for CH and 70.3 °C for NFH) and prolonging the thermophilic phase. NFH also showed stronger moisture removal, with the final moisture content decreasing to 58.1%, compared with 65.1% in CH and 64.1% in the control. CH showed the highest apparent humic acid accumulation (1173 mg kg⁻¹), whereas NFH exhibited spectroscopic features commonly associated with lower E₄/E₆ ratios and more pronounced humic-like fluorescence characteristics. Ultraviolet–visible spectroscopy (UV–Vis), Fourier transform infrared spectroscopy (FTIR), and excitation–emission matrix fluorescence spectroscopy (EEM) analyses collectively indicated progressive transformation toward more aromatic and humified organic matter in the amended treatments. Bacterial community succession also differed across treatments, and several enriched taxa, including Rhodanobacter and Thermobifida, showed positive associations with reactive oxygen species (ROS)-related variables and humification indices. These results describe treatment-linked dynamics in humification and suggest corresponding changes in microbial succession during sludge composting, with potential implications for process outcomes. Full article

The industrial extraction of chitin from shrimp shell waste conventionally employs corrosive chemical treatments, which pose significant environmental hazards and compromise polymer integrity. This study introduces a sustainable and highly efficient microbial biorefining strategy for the recovery of α-chitin from Litopenaeus vannamei shells, utilizing a sequential fermentation framework. Two potent strains—Bacillus haynesii MGPUMGRI, known for its proteolytic capabilities, and Lactobacillus delbrueckii MGPUMGRI, which produces lactic acid—were isolated and optimized. A notable technical achievement was the purification of an approximately 40 kDa extracellular alkaline protease from B. haynesii, which demonstrated optimal activity at pH 9.0 and 37 °C. Under optimized conditions, the sequential process—emphasizing enzymatic deproteinization (72.30 ± 1.56%) followed by lactic acid-mediated demineralization (84.98 ± 1.96%)—achieved a high-purity chitin recovery of 61.33 ± 1.06%. Comprehensive characterization using SEM-EDX, FTIR, and XRD confirmed the successful preservation of the α-chitin polymorphic structure, which exhibited a fragmented fibrillar morphology and a crystallinity index (CrI) of 60.51%. These findings indicate that this dual-strain bioprocess offers a scalable and environmentally friendly alternative for the valorization of seafood waste into high-quality biogenic polymers, while minimizing the ecological impact of chitin production. Full article

Radiation plays an important role in the treatment of many solid tumors. While conventional fractionation schedules are commonly used, technological advances have allowed safer and more effective dose escalation in the treatment of both primary as well as metastatic lesions. There is growing evidence about the intricate role played by the immune system in modulating the effect of cancer treatment, and several pre-clinical and clinical studies have explored the use of immunotherapy in the treatment of various cancers, both in the metastatic and upfront treatment setting. This approach has shown significant success in the management of melanomas and lung cancers and has prompted exploration of the same strategy in many other cancer subtypes. Radiation has been proposed to synergize the effect of immunotherapy through various mechanisms and is currently being evaluated in various ongoing clinical trials. Several mature clinical studies have also shown significant benefit with the combination and have led to its uptake in routine clinical practice. Furthermore, the use of hypo-fractionated high-dose radiation or Stereotactic Body Radiation Treatment (SBRT) regimens have shown benefits over conventional radiation in this context and are being actively explored as a treatment strategy. Full article

Background: Lentigo maligna (LM) represents melanoma in situ and predominantly affects elderly individuals, typically arising on chronically sun-exposed skin of the head and neck. Although LM is characterized by slow horizontal growth and generally favourable prognosis, progression to invasive lentigo maligna melanoma may occur, making timely and effective treatment essential. Surgical excision remains the standard of care; however, advanced age, comorbidities, lesion size, and cosmetic or functional considerations may limit surgical feasibility. Case presentation: We report the case of a 93-year-old woman with no prior history of skin cancer who presented with a gradually enlarging pigmented lesion on the forehead. Clinical examination revealed an irregularly pigmented macule measuring 25 × 27 mm. Multiple mapping biopsies confirmed melanoma in situ of the lentigo maligna type, with adnexal extension and no evidence of dermal invasion. Given the patient’s advanced age and lesion location, a non-surgical approach was selected. Topical imiquimod 5% cream was applied five times per week for 12 weeks to the visible lesion and to a 20 mm margin around it. The patient was monitored closely throughout the treatment. Local inflammatory reactions were mild to moderate, consisting mainly of erythema, crusting, and superficial erosion, without systemic adverse effects. At treatment completion, marked clinical improvement with near-complete resolution of pigmentation was observed. Follow-up dermoscopic evaluation demonstrated only minimal residual granular pigmentation. Post-treatment mapping biopsies confirmed complete histological clearance of atypical melanocytic cells. Conclusions: This case illustrates that topical imiquimod may serve as a safe and effective alternative to surgery in carefully selected elderly patients with lentigo maligna. Close clinical follow-up and histological confirmation of clearance are essential to ensure treatment success and durable outcomes. Full article

Climate change represents one of the most critical challenges, especially in the Mediterranean area. Using organic and localized fertilization could be an effective agroecological strategy to help mitigate the environmental impacts of climate change. Our study was carried out in an experimental field over a three-year crop succession including broccoli, sweet pepper and barley. A randomized complete block design was adopted, with two factors: (i) fertilization method (100% broadcast and 40% localized) and (ii) fertilizer type by testing: on-farm compost, two types of commercial compost and a mineral fertilizer. Environmental impacts per hectare and marketable yield were quantified using Life Cycle Assessment (LCA), considering abiotic depletion (AD), acidification (AA), eutrophication (EU), global warming potential (GWP), and photochemical oxidation (PO). The localized application of fertilizers achieved marketable yields comparable to the broadcast method, despite lower fertilizer inputs, suggesting an optimal nutrient-use efficiency. The LCA demonstrated that localized fertilization also enhanced environmental sustainability, decreasing Global Warming Potential (GWP) by 20% per hectare, compared to broadcast treatments. Moreover, considering only the fertilization phase, we observed a 59% reduction in GWP under the localized strategy. Even though localized fertilization emerges as an effective climate-smart strategy without compromising productivity, future research is recommended to assess its long-term impacts in site-specific conditions. Full article

The aquaculture of Octopus vulgaris faces high larval mortality, mainly due to nutritional limitations and susceptibility to pathogens, particularly Vibrio spp. As vaccination is not feasible in cephalopods, host-associated probiotics represent a promising and sustainable alternative to improve survival and reduce infections. This study evaluated bacteria from the Roseobacter clade as probiotic candidates during octopus embryonic and paralarval stages. Characterization of egg-associated microbiota revealed the absence of cultivable bacteria within eggs and a significantly lower bacterial load on egg surfaces under maternal care, highlighting the regulatory role of female cleaning behavior. No bacteria with antagonism against Vibrio lentus, a common pathogen to octopus, were isolated from egg surfaces. Therefore, selected Roseobacter clade strains were screened in vitro against relevant aquaculture pathogens. Phaeobacter strains showed strong inhibitory activity against Vibrio spp., including V. lentus, while Ruegeria strains exhibited higher specificity against Tenacibaculum maritimum. Based on these results, Phaeobacter sp. 4UAC3 was selected for in vivo assays. This strain successfully colonized eggs, water, and paralarvae; however, its application reduced hatching success in eggs by 33%, likely due to surface-associated accumulation of the bacteria linked to the administration method. In contrast, probiotic treatment significantly improved survival at the paralarval stage. Although high variability was observed, probably due to stressful rearing conditions, more than 50% was observed in treated vs. 0% in non-treated cases at day 6. Overall, Phaeobacter sp. 4UAC3 emerges as a promising probiotic candidate to improve O. vulgaris paralarvae survival, potentially contributing to solving this bottleneck in a sustainable way. Full article

The Southern Stuttering Frog, Mixophyes australis, is a newly described threatened species endemic to Australia that is suffering severe and ongoing declines. The species is currently presumed extinct from the southern two thirds of its range, primarily driven by the amphibian chytrid fungus (Batrachochytrium dendrobatidis; Bd). In response to the species’ decline, a conservation breeding program (CBP) was established at Symbio Wildlife Park to secure an insurance population and support future reintroductions. Herein, the establishment and management of the CBP for M. australis is described. We detail the captive husbandry framework and tracing progress from the collection of 200 wild-caught tadpoles in April 2022, through to the successful reproduction of the founder colony. Following the revision of husbandry and water management practices, and disease treatment in quarantine to overcome initial mortality, 89 Bd-free individuals were transferred to the breeding facility to establish the insurance colony. Critically, the program has achieved consistent and successful reproduction commencing in April 2024, within 2 years of tadpole collection. The breeding cohort exhibited a distinctive bimodal annual reproductive pattern in captivity, with clear peaks in breeding activity in Austral autumn (March–May) and mid-winter to early spring (July–September). We detail effective husbandry protocols for all life stages of the species, which has resulted in the generation of clutches exhibiting high fertility and high tadpole survivorship. Overall, the program to date has contributed to the reintroduction of over 7700 first-generation (F1) tadpoles and 59 head-started founder (F0) adults across 15 release sites within the species’ historical range in NSW. Herein, we provide important natural history data for the species and considerations for their breeding in captivity, which can inform future conservation efforts for this and other threatened frog species globally. Full article

Background: This study investigates textbook oncologic outcomes (TOO), a measurement operationally defined to produce a holistic measure of surgical success, with respect to patients diagnosed with pancreatic adenocarcinoma undergoing distal (left) pancreatectomy for pancreatic adenocarcinoma. This study aims to identify factors associated with achieving TOO, emphasizing the role of hospital type. Methods: The NCDB (2010–2022) was queried for patients with clinical stage I–III pancreatic adenocarcinoma. Inclusion criteria consisted of patients > 18 who underwent curative partial or total pancreatectomy. The primary outcome was the achievement of TOO—operationally defined as R0 resection, ≥12 lymph nodes examined, no prolonged hospital stay, absence of 30-day mortality, and no readmissions. Logistic regression analyses were conducted to identify predictors of TOO. Results: Analysis of 11,194 patients showed that 38.9% achieved TOO. Achievement of TOO was associated with a median increase in one year in overall survival. Factors associated with TOO achievements in the adjusted model include female sex, private insurance, a lower Charlson/Deyo score, minimally invasive surgery (MIS), and high-volume centers. Notably, MIS emerged as a significant factor associated with 26% higher TOO (OR 1.26, 95% CI: 1.14–1.40) while treatment at high-volume hospitals was associated with 28–112% increased TOO (OR 1.28, 95% CI: 1.08–1.54 for Q3 volume and OR 2.12, 95% CI: 1.76–2.55 for Q4 volume). Conclusions: Achieving TOO is significantly influenced by patient demographics, clinical characteristics, and notably, the case volume of the treatment facility. These findings underscore the importance of considering centers experienced in surgical planning and patient counseling to optimize outcomes in distal pancreatectomies. Full article

Introduction: platelet-rich fibrin (PRF) is a second-generation platelet concentrate which is known for promoting cell migration, tissue repair, angiogenesis and bone formation. In contrast, the specific effects of trauma-activated PRF on mesenchymal stromal cells (MSC) are not yet fully understood. The present study investigates systemic effects of surgical trauma-activated PRF on MSCs in vitro, analyzing their metabolic activity, inflammatory responses, and regenerative capacity to optimize advanced treatment concepts for severe fractures and injuries. Material & Methods: PRF membranes (T-PRF from trauma patients, C-PRF from healthy controls) were generated. After co-incubation with MSC cells for 24, 72, and 120 h, further investigations of metabolic activity (MTT assay) and gene expression analyses were performed. Results: for MTT assay, results especially showed a significantly higher metabolic activity of T-PRF after 120 h. ELISA-results measuring cytokine levels (CXCL10, IL-6, VEGF, and IDO) exposed a frequent peak in T-PRF group at 72 h, declining slightly at 120 h. In the gene expression analyses, T-PRF exerted a comparatively stronger stimulating effect on MAPK14 and VEGFA after 24 h, while a decrease in gene expression for MAPK8, MAPK14, and RUNX2 was observed over time. Conclusion: surgical trauma-activated PRF seems to be a powerful inducer of early inflammatory and stress responses in MSCs with preserved angiogenic but limited osteogenic signaling. Therefore, a targeted balance between inflammatory activation and sustainable regeneration, as well as optimized preparation and possible combination with immunomodulatory approaches, appear to be crucial for the therapeutic success of PRF-based strategies. Full article

Background/Objectives: Oritavancin therapy for complex infections remains challenging due to the lack of well-established dosing regimens. The objective of this work was to apply PK/PD modeling and Monte Carlo simulation considering different PK/PD targets to identify multiple-dosing regimens that may ensure effective concentrations of oritavancin for the treatment of long-term infections. Methods: Plasma concentration–time profiles were simulated for different regimens (single dose of 1200 mg, 1200 mg followed by 800 mg every 7 days (q7d), 1200 mg followed by 800 mg q10d, 1200 mg q7d, 1200 mg q10d, 1200 mg q14d, 1200 mg q21d, and 1200 mg followed by 1200 mg on day 8, then 1200 mg q14d), and the probability of target attainment (PTA), indicative of treatment success, was estimated. Results: All dosing regimens provided probabilities of target attainment of 100% up to MICs of 0.5 mg/L when AUC_0–24/MIC and C_max/MIC were applied. Considering AUC_0–72/MIC, the regimens would be adequate up to an MIC of 0.125 mg/L. For fC_min > MIC, all except 1200 mg q21d were adequate for an MIC of 0.125 mg/L, and 1200 mg day 1 + 800 mg q7d and 1200 mg q10d may be useful to treat infections due to bacteria with an MIC of 0.25 mg/L. Conclusions: More studies involving patients with complex infections are needed to better stablish the relationships among plasma concentrations, MIC values, and clinical outcomes. fC_min > MIC should be investigated as a potential PK/PD target for the treatment of these infections with oritavancin. Full article