The role of neophobia in a pioneer olfactory enrichment for amazons, macaws, and toucans / El papel de la neofobia en un enriquecimiento olfativo pionero para guacamayos, loros y tucanes

Abstract Introduction: Despite sensory enrichment being critical for ensuring the well-being of captive wild animals, smells are not being included in enrichment protocols for birds. For this group, neophobia can be a problem when it comes to implementing new enrichment devices. Objective: To explore how participation in an olfactory enrichment and latency times varies between bird taxonomic groups (Amazona spp. / Ara spp. / Ramphastos spp.). Methods: We exposed 257 birds to a scent enrichment, and we recorded which individuals engaged with it and the time they took to interact with it. Results: We discovered that participation by toucans in the enrichment was higher compared to amazons and macaws. Furthermore, latency time to interact with the enrichment was higher in amazons that in the other species. Our findings could suggest that toucans are neophilic species which could benefit from higher exploration rates. Amazons on the contrary seem to be particularly neophobic, possibly because of their less opportunistic feeding habits compared to toucans and their higher vulnerability to predation compared to macaws. Conclusion: These results point out that toucans would be more inclined to engage in environmental enrichments, while a more natural design using smells inside familiar objects could be a more successful enrichment for psittacids.

Resumen Introducción: A pesar de que el enriquecimiento sensorial es fundamental para garantizar el bienestar de los animales silvestres en cautiverio, los olores no son incluidos de forma rutinaria en los protocolos de enriquecimiento para aves. Además, en el caso de estos animales, la neofobia puede ser un problema a la hora de implementar nuevos dispositivos de enriquecimiento. Objetivo: Explorar cómo varía la participación y la latencia en la interacción con un enriquecimiento olfativo entre grupos taxonómicos de aves (Amazona spp. / Ara spp. / Ramphastos spp.). Métodos: Expusimos a 257 aves a un enriquecimiento olfativo y registramos qué individuos participaron y el tiempo que tardaron en interactuar con él. Resultados: La participación en el enriquecimiento fue mayor en los tucanes en comparación con las amazonas y los guacamayos. Además, el tiempo de latencia para interactuar con el enriquecimiento fue mayor en las amazonas que en las otras especies. Nuestros hallazgos sugieren que los tucanes son especies neofílicas que podrían beneficiarse de tasas de exploración más altas. Por otro lado, las amazonas parecen ser particularmente neofóbicas, posiblemente debido a sus hábitos alimenticios menos oportunistas en comparación con los tucanes y a su mayor vulnerabilidad a la depredación en comparación con los guacamayos. Conclusión: Estos resultados señalan que los tucanes serían más proclives a participar en enriquecimientos ambientales, mientras que un diseño que utilice olores dentro de objetos más naturales o familiares podría ser más exitoso para las psitácidas.

When birds of a feather flock together: Severe genomic erosion and the implications for genetic rescue in an endangered island passerine.

The Seychelles magpie-robin's (SMR) five island populations exhibit some of the lowest recorded levels of genetic diversity among endangered birds, and high levels of inbreeding. These populations collapsed during the 20th century, and the species was listed as Critically Endangered in the IUCN Red List in 1994. An assisted translocation-for-recovery program initiated in the 1990s increased the number of mature individuals, resulting in its downlisting to Endangered in 2005. Here, we explore the temporal genomic erosion of the SMR based on a dataset of 201 re-sequenced whole genomes that span the past ~150 years. Our sample set includes individuals that predate the bottleneck by up to 100 years, as well as individuals from contemporary populations established during the species recovery program. Despite the SMR's recent demographic recovery, our data reveal a marked increase in both the genetic load and realized load in the extant populations when compared to the historical samples. Conservation management may have reduced the intensity of selection by increasing juvenile survival and relaxing intraspecific competition between individuals, resulting in the accumulation of loss-of-function mutations (i.e. severely deleterious variants) in the rapidly recovering population. In addition, we found a 3-fold decrease in genetic diversity between temporal samples. While the low genetic diversity in modern populations may limit the species' adaptability to future environmental changes, future conservation efforts (including IUCN assessments) may also need to assess the threats posed by their high genetic load. Our computer simulations highlight the value of translocations for genetic rescue and show how this could halt genomic erosion in threatened species such as the SMR.

Emergency management of pediatric epileptic seizures in non-hospital settings in Japan.

OBJECTIVE: To assess the current management of pediatric epileptic seizures in non-hospital settings and the efficacy of early therapeutic intervention with rescue medication in Japan. METHODS: This descriptive cross-sectional study was based on an online survey of caregivers of pediatric patients with epilepsy. The survey consisted of questions regarding seizure frequency and symptoms, the use of rescue medication, and emergency medical care. Statistical analyses were performed to evaluate the association between the time to rescue medication administration and seizure resolution. RESULTS: Responses were obtained from 1147 caregivers of pediatric patients with epilepsy. Of the patients described in the study, 98.5 % had been prescribed anti-seizure medication, 95.3 % had more than a few seizures per year, and 90.3 % used rescue medication. The time to seizure resolution was significantly reduced when rescue medication was administered early. Overall, 28.4 % of the patients required emergency transport to hospital, which increased disruption to the lives of caregivers, who returned to their normal activities after an average of 17.2 h. CONCLUSION: Emergency transport of patients places a significant burden on caregivers. Earlier administration of rescue medications is associated with a reduction in the need for emergency room visits, which reduces the burden on the patient as well as the caregiver.

Failure to rescue following emergency general surgery: A national analysis.

Background: Failure to rescue (FTR) is increasingly recognized as a quality metric but remains understudied in emergency general surgery (EGS). We sought to identify patient and operative factors associated with FTR to better inform standardized metrics to mitigate this potentially preventable event. Methods: All adult (≥18 years) non-elective hospitalizations for large bowel resection, small bowel resection, repair of perforated ulcer, laparotomy and lysis of adhesions were identified in the 2016-2020 National Readmissions Database. Patients undergoing trauma-related operations or procedures ≤2 days of admission were excluded. FTR was defined as in-hospital death following acute kidney injury requiring dialysis (AKI), myocardial infarction, pneumonia, respiratory failure, sepsis, stroke, or thromboembolism. Multilevel mixed-effect models were developed to assess factors linked with FTR. Results: Among 826,548 EGS operations satisfying inclusion criteria, 298,062 (36.1 %) developed at least one MAE. Of those experiencing MAE, 43,477 (14.6 %) ultimately did not survive to discharge (FTR). Following adjustment for fixed hospital level effects, only 3.5 % of the variance in FTR was attributable to center-level differences. Relative to private insurance and the highest income quartile, Medicaid insurance (AOR 1.33; 95%CI, 1.23-1.43) and the lowest income quartile (AOR 1.22; 95%CI, 1.17-1.29) were linked with increased odds of FTR.A subset analysis stratified complication-specific rates of FTR by insurance status. Relative to private insurance, Medicaid coverage and uninsured status were linked with greater odds of FTR following perioperative sepsis, pneumonia, and AKI. Conclusion: Our findings underscore the need for increased screening and vigilance following perioperative complications to mitigate disparities in patient outcomes following high-risk EGS.

HBS1L deficiency causes retinal dystrophy in a child and a mouse model associated with defective development of photoreceptor cells.

Inherited retinal diseases encompass a genetically diverse group of conditions caused by mutations in genes critical to retinal function, including handful of ribosome-associated genes. This study focuses on HBS1L gene which encodes for HBS1-like translational GTPase crucial for ribosomal rescue. We have reported a female child carrying biallelic HBS1L variants, manifesting with poor growth and neurodevelopmental delay. Here we describe the ophthalmologic findings in the patient and Hbs1ltm1a/tm1a hypomorph mice and describe the associated microscopic and molecular perturbations. The patient has impaired visual function, showing dampened amplitudes of a- and b-waves in both rod- and cone-mediated responses. Hbs1ltm1a/tm1a mice exhibited profound thinning of the entire retina, specifically of the outer photoreceptor layer, due to extensive photoreceptor cell apoptosis. Loss of HBS1L resulted in comprehensive proteomic alterations on mass spectrometry analysis, with 169 proteins increased and 480 decreased including rhodopsin and peripherin 2. GO biological process and GSEA analyses reveal that the downregulated proteins are primarily involved in phototransduction, cilium assembly, and photoreceptor cell development. These findings underscore the importance of ribosomal rescue proteins in maintaining retinal health, particularly in photoreceptor cells.

Ovarian function in female survivors of high-risk neuroblastoma.

INTRODUCTION: Data on ovarian function in neuroblastoma survivors are limited. We sought to determine the prevalence of ovarian dysfunction in a cohort of high-risk neuroblastoma survivors and compare outcomes among survivors treated with and without autologous stem cell rescue (ASCR) preceded by myeloablative chemotherapy. METHODS: Retrospective review of female survivors of high-risk neuroblastoma ≥5 years from diagnosis, diagnosed between 1982 and 2014, and followed in a tertiary cancer center. Participants were divided into two groups: individuals treated with conventional chemotherapy ± radiation ("non-ASCR") (n = 32) or with chemotherapy ± radiation followed by myeloablative chemotherapy with ASCR ("ASCR") (n = 51). Ovarian dysfunction was defined as follicle-stimulating hormone ≥15 mU/mL, while premature ovarian insufficiency (POI) was defined as persistent ovarian dysfunction requiring hormone replacement therapy. Poisson models were used to determine prevalence ratios of ovarian dysfunction and POI. RESULTS: Among 83 females (median attained age: 19 years [range, 10-36]; median follow-up: 15 years [range, 7-36]), 49 (59%) had ovarian dysfunction, and 34 (41%) developed POI. Survivors treated with ASCR were 3.2-fold more likely to develop ovarian dysfunction (95% CI: 1.8-6.0; p < 0.001) and 4.5-fold more likely to develop POI (95% CI: 1.7-11.7; p = 0.002) when compared with those treated with conventional chemotherapy, after adjusting for attained age. Two participants in the non-ASCR group and six in the ASCR group achieved at least one spontaneous pregnancy. DISCUSSION: Ovarian dysfunction is prevalent in female high-risk neuroblastoma survivors, especially after ASCR. Longitudinal follow-up of larger cohorts is needed to inform counseling about the risk of impaired ovarian function after neuroblastoma therapy.

Rescue Therapies for Steroid-Refractory Acute Severe Ulcerative Colitis: A Systemic Review and Network Meta-analysis.

BACKGROUND AND AIMS: Approximately 40% of patients with steroid-refractory acute severe ulcerative colitis (steroid-refractory (SR) ASUC) requires colectomies. Advanced therapies may reduce the short-term colectomy rates in patients with SR ASUC. However, comparative clinical studies evaluating the effectiveness of these rescue therapies are lacking. Therefore, we conducted a network meta-analysis to study the effectiveness of rescue therapies for SR ASUC. METHODS: Six randomized controlled trials and 15 cohort studies including 2,004 patients were analyzed. Rescue drugs included tofacitinib, infliximab with a 5 or 10 mg/kg induction dose at 0, 2, and 6 weeks (IFX and IFX10, respectively), IFX with an accelerated regimen of three 5 mg/kg induction doses timed according to clinical need (accelerated IFX), tacrolimus, cyclosporine (CyA), ustekinumab, and adalimumab. Treatments were compared with a placebo. RESULTS: Tofacitinib (odds ratio [OR]: 0.09 [95% confidence interval [CI]: 0.02-0.52]), accelerated IFX (OR: 0.16 [95% CI: 0.03-0.94]), IFX (OR: 0.2 [95% CI: 0.07-0.58]), and tacrolimus (OR: 0.24 [95% CI: 0.06-0.96]) significantly reduced the short-term colectomy rates compared with placebo. IFX10 and CyA tended to prevent colectomies. However, ustekinumab and adalimumab did not significantly affect the colectomy rates. CONCLUSION: This is the first network meta-analysis to investigate the efficacy of advanced therapies in reducing short-term colectomy rates in patients with SR ASUC. Tofacitinib, accelerated IFX, standard IFX, and tacrolimus significantly reduced the colectomy rates in SR ASUC patients compared with placebo. Thus, advanced therapies should be considered for rescue therapies in patients with SR ASUC.

Epidemiological investigation of foot-and-mouth disease outbreaks in a Vietnamese bear rescue centre.

Foot-and-mouth disease (FMD) outbreaks affecting Asiatic black bears (Ursus thibetanus) and a Malayan sun bear (Helarctos malayanus) were previously reported in 2011 in two housing facilities at a Vietnamese bear rescue centre. In this study, demographic data of all animals housed in the centre at the time of the outbreaks (n = 79) were collected. Blood samples drawn from 23 bears at different timepoints were tested for FMDV-specific antibodies targeting using a non-structural protein (NSP) ELISA and by virus neutralisation test (VNT). The relationship between seroconversion and clinical signs was explored and epidemic curves and transmission diagrams were generated for each outbreak, where FMD cases were defined as animals showing FMD clinical signs. Outbreak-specific attack rates were 18.75 and 77.77%, with corresponding basic reproduction numbers of 1.11 and 1.92, for the first and second outbreaks, respectively. Analyses of risk factors showed that after adjusting for sex there was strong evidence for a decrease in odds of showing clinical signs per year of age. All samples collected from bears before the outbreak tested negative to NSP and VNT. All cases tested positive to VNT following onset of clinical signs and remained positive during the rest of the follow up period, while only 6 out of 17 cases tested positive to NSP after developing clinical signs. Six animals without clinical signs were tested post outbreaks; five seroconverted using VNT and three animals were seropositive using NSP ELISA. This study provides initial epidemiological parameters of FMD in captive bears, showing that FMDV is easily spread between bears in close proximity and can cause clinical and subclinical disease, both of which appear to induce rapid and long-lasting immunity.

Failure to Rescue After Percutaneous Coronary Intervention: Insights From the National Cardiovascular Data Registry.

BACKGROUND: Failure to rescue (FTR) describes in-hospital mortality following a procedural complication and has been adopted as a quality metric in multiple specialties. However, FTR has not been studied for percutaneous coronary intervention (PCI) complications. METHODS: This is a retrospective study of patients undergoing PCI from the American College of Cardiology National Cardiovascular Data Registry's CathPCI Registry between April 1, 2018, and June 30, 2021. PCI complications evaluated were significant coronary dissection, coronary artery perforation, vascular complication, significant bleeding within 48 hours, new cardiogenic shock, and tamponade. Secular trends for FTR were evaluated with descriptive analysis, and hospital-level variation and clinical predictors were analyzed with logistic regression. RESULTS: Among 2 196 661 patients undergoing PCI at 1483 hospitals, 3.5% had at least 1 PCI complication. In-hospital mortality occurred more frequently following a complication compared with cases without a complication (19.7% versus 1.3%). FTR increased during the study period from 17.1% to 20.1% (P<0.001). The median odds ratio for FTR was 1.48 (95% CI, 1.44-1.53) indicating significant hospital-level variation. Spearman rank correlation demonstrated the modest correlation between FTR and in-hospital mortality, 0.525 (P<0.001). CONCLUSIONS: Major procedural complications during PCI are infrequent, but FTR occurs in roughly 1 in 5 patients following a PCI procedural complication with significant hospital-level variation. Improved understanding of practices associated with low FTR could meaningfully improve patient outcomes following a PCI complication.

Structure-Activity Relationships of the Fentanyl Scaffold: Identification of Antagonists as Potential Opioid Overdose Reversal Agents.

Opioid-related overdoses account for almost half of all drug overdose deaths in the United States and cause more preventable deaths every year than car crashes. Fentanyl, a highly potent mu opioid receptor (MOR) agonist and its analogues (fentalogues) are increasingly found in illicit drug samples, both where the primary drug of abuse is an opioid and where it is not. The prevalence of fentalogues in the illicit drug market is thought to be the primary driver of the increased number of opioid-related overdose deaths since 2016. In fact, fentanyl and its analogues are involved in more than 70% of opioid-related overdoses. The standard opioid overdose rescue therapy naloxone is often insufficient to reverse opioid overdoses caused by fentalogue agonists under current treatment paradigms. However, the pharmacology of many fentalogues is unknown. Moreover, within the fentalogue series of compounds, it is possible that antagonists could be identified that might be superior to naloxone as opioid overdose reversal agents. In this report, we explore the pharmacology of 70 fentalogues and identify compounds that behave as MOR antagonists in vitro and demonstrate with one of these reversals of fentanyl-induced respiratory depression in the mouse. Such compounds could provide leads for the development of effective agents for the reversal of opioid overdose.

Surveillance after surgery for pancreatic cancer: a global scoping review of guidelines and a nordic Survey of contemporary practice.

OBJECTIVES: Most patients with pancreatic cancer who have undergone surgical resection eventually develop disease recurrence. |This study aimed to investigate whether there is evidence to support routine surveillance after pancreatic cancer surgery, with a secondary aim of analyzing the implementation of surveillance strategies in the Nordic countries. MATERIALS AND METHODS: A scoping review was conducted to identify clinical practice guidelines globally and research studies relating to surveillance after pancreatic cancer resection. This was followed by a survey among 20 pancreatic units from four Nordic countries to assess their current practice of follow-up for operated patients. RESULTS: Altogether 16 clinical practice guidelines and 17 research studies were included. The guidelines provided inconsistent recommendations regarding postoperative surveillance of pancreatic cancer. The clinical research data were mainly based on retrospective cohort studies with low level of evidence and lead-time bias was not addressed. Active surveillance was recommended in Sweden and Denmark, but not in Norway beyond the post-operative/adjuvant period. Finland had no national recommendations for surveillance. The Nordic survey revealed a wide variation in reported practice among the different units. About 75% (15 of 20 units) performed routine postoperative surveillance. Routine CA 19-9 testing was used by 80% and routine CT by 67% as part of surveillance. About 73% of centers continued follow-up until 5 years postoperatively. CONCLUSION: Evidence for routine long-term (i.e. 5 years) surveillance after pancreatic cancer surgery remains limited. Most pancreatic units in the Nordic countries conduct regular follow-up, but protocols vary.

Improving Quality of Care for Status Epilepticus: Putting Protocols into Practice.

PURPOSE OF REVIEW: Timely treatment of status epilepticus (SE) improves outcomes, however gaps between recommended and implemented care are common. This review analyzes obstacles and explores interventions to optimize effective, evidence-based treatment of SE. RECENT FINDINGS: Seizure action plans, rescue medications, and noninvasive wearables with seizure detection capabilities can facilitate early intervention for prolonged seizures in the home and school. In the field, standardized EMS protocols, EMS education, and screening tools can address variability in SE definitions and treatment, particularly benzodiazepine dosing. In the emergency room and hospital, provider education, SE order sets and alerts, and rapid EEG technologies, can shorten time to first-line therapy, second-line therapy, and EEG initiation. Widespread, sustained improvement in SE care remains challenging. A multipronged approach including emphasis on pre-hospital intervention, treatment protocols adapted to local contexts, and SE databases to systematically collect process and outcome metrics have the potential to transform SE treatment and outcomes.

Antiviral combination regimens as rescue therapy in immunocompromised hosts with persistent COVID-19.

The management of severe/prolonged SARS-CoV-2 infections in immunocompromised hosts is still challenging. We describe nine patients with hematologic malignancies with a history of unsuccessful SARS-CoV-2 treatment receiving antiviral combination treatment for persistent infection at a tertiary hospital in central Italy (University Hospital of Careggi, Florence). Combination treatments consisted of nirmatrelvir/ritonavir plus molnupiravir (n = 4), nirmatrelvir/ritonavir plus remdesivir (n = 4) or remdesivir plus molnupiravir (n = 1) for 10 days, in some cases associated with sotrovimab. Combinations were generally well tolerated. One patient obtained viral clearance but died due to the underlying disease. In eight cases, clinical and virological success was confirmed by radiological follow-up. Antivirals combination is likely to become a mainstay in the future management of COVID-19 among immunocompromised patients, but knowledge in this field is still very limited and prospective studies on larger cohorts are urgently warranted.

The Outcome of Walking Cold Patients with Potential Mild Hypothermia to Safety-A Mountain Rescue Case Series.

INTRODUCTION: Some experts recommend that ambulant hypothermic patients should be rewarmed, fed, and not permitted to exercise for 30 min because of concerns that afterdrop can cause cardiac instability. We investigated the outcome of ambulant hypothermic patients in a case series from mountain rescue teams in Great Britain. METHODS: A questionnaire was used to collect information on a series of adult patients with a clinical diagnosis of mild hypothermia. All patients were alert on the AVPU scale and evacuated by walking from the mountain. The outcome measures were survival or a change in management because of medical deterioration during evacuation. RESULTS: A series of 108 eligible cases were reported over a 5-year period. When rescuers arrived on the scene, 98 (91%) patients were stationary, and 10 (9%) were still mobile. Thirty-eight (39%) of the stationary cases were walked immediately off the mountain without any on-scene delay. In the remaining 60 (61%) stationary cases, the decision was taken to delay evacuation to provide food, drinks, and additional clothing. In 3 cases, the use of heat packs indicated an intention to actively rewarm. In cases where the on-scene time was reported, 27 (79%) were known to be mobile again within 20 min. All patients survived, and no adverse medical events occurred in all 108 cases. CONCLUSIONS: In this study, no adverse events occurred because of immediate mobilization, suggesting that in these cases, there appears to be minimal risk of early activity.

Effect of different reperfusion strategies on recovery of ventricular function after ST-segment elevation myocardial infarction: A longitudinal single-center study.

Background and Aims: Although the clinical benefit of percutaneous coronary intervention (PCI) on cardiovascular outcomes has been widely investigated, the impact of this revascularization strategy compared to other alternatives on the degree of left ventricular function recovery is poorly demonstrated. In this regard, we investigated whether time delays between the presentation of ST-segment elevation myocardial infarction (STEMI) and PCI in reperfusion strategies have different impacts on left ventricular function recovery. Methods: In this single-center study, all the patients who presented with STEMI and a reduced left ventricular ejection fraction (LVEF ≤ 40%) were enrolled. Included patients were subjected to four different treatment groups of primary, rescue (immediate transfer for angioplasty due to failed fibrinolytic therapy), facilitated (fibrinolytic therapy followed by angioplasty within 24 h), and deferred (successful fibrinolytic therapy and PCI after 24 h) PCI based on hospital facilities. Echocardiography was performed for all the patients at the time of hospitalization and 6 months later. Results: A total of 128 patients were included in this study. The LVEF improved by 15.3 ± 6.3%, 11.5 ± 3.61%, 4.0 ± 1.0%, and -1.3 ± 7.0% in primary, rescue, facilitated, and deferred PCI groups, respectively (p < 0.001). Patients undergoing deferred PCI experienced a significantly lower improvement in LVEF compared with primary and rescue PCI (p < 0.001). Conclusion: Primary PCI demonstrated the most promising recovery in left ventricular function following STEMI compared to other alternative strategies. Performing PCI as soon as possible provides better recovery of LVEF.

Amelioration of Fibrosis via S1P Inhibition Is Regulated by Inactivation of TGF-ß and SPL Pathways in the Human Cornea.

Human corneal fibrosis can lead to opacity and ultimately partial or complete vision loss. Currently, corneal transplantation is the only treatment for severe corneal fibrosis and comes with the risk of rejection and donor shortages. Sphingolipids (SPLs) are known to modulate fibrosis in various tissues and organs, including the cornea. We previously reported that SPLs are tightly related to both, transforming growth factor beta (TGF-ß) signaling and corneal fibrogenesis. The aim of this study was to investigate the effects of sphingosine-1-phosphate (S1P) and S1P inhibition on specific TGF-ß and SPL family members in corneal fibrosis. Healthy human corneal fibroblasts (HCFs) were isolated and cultured in EMEM + FBS + VitC (construct medium) on 3D transwells for 4 weeks. The following treatments were prepared in a construct medium: 0.1 ng/mL TGF-ß1 (ß1), 1 µM sphingosine-1-phosphate (S1P), and 5 µM Sphingosine kinase inhibitor 2 (I2). Five groups were tested: (1) control (no treatment); rescue groups; (2) ß1/S1P; (3) ß1/I2; prevention groups; (4) S1P/ß1; and (5) I2/ß1. Each treatment was administered for 2 weeks with one treatment and switched to another for 2 weeks. Using Western blot analysis, the 3D constructs were examined for the expression of fibrotic markers, SPL, and TGF-ß signaling pathway members. Scratch assays from 2D cultures were also utilized to evaluate cell migration We observed reduced fibrotic expression and inactivation of latent TGF-ß binding proteins (LTBPs), TGF-ß receptors, Suppressor of Mothers Against Decapentaplegic homologs (SMADs), and SPL signaling following treatment with I2 prevention and rescue compared to S1P prevention and rescue, respectively. Furthermore, we observed increased cell migration following stimulation with I2 prevention and rescue groups, with decreased cell migration following stimulation with S1P prevention and rescue groups after 12 h and 18 h post-scratch. We have demonstrated that I2 treatment reduced fibrosis and modulated the inactivation of LTBPs, TGF-ß receptors, SPLs, and the canonical downstream SMAD pathway. Further investigations are warranted in order to fully uncover the potential of utilizing SphK I2 as a novel therapy for corneal fibrosis.

Options for Rescue Treatment of Patients with AL Amyloidosis Exposed to Upfront Daratumumab.

PURPOSE OF REVIEW: This review aims to assess the therapeutic strategies available for relapsed/refractory patients with immunoglobulin light chain (AL) amyloidosis who received upfront daratumumab-based regimens. RECENT FINDINGS: The treatment landscape of AL amyloidosis has changed radically thanks to the introduction in the upfront setting of daratumumab in combination with bortezomib, cyclophosphamide and dexamethasone (DaraCyBorD) which improved patients' outcomes increasing the rate of hematologic and organ responses. However, many patients eventually relapse or are refractory to daratumumab and the best salvage therapy is not well defined yet. In this contest, we reviewed the available therapeutic options after daratumumab failure, and we look towards the current advances in Bcl-2 inhibitors, novel immunotherapeutic agents as chimeric antigen receptor (CAR-T) therapy and bispecific antibodies (bsAbs). Relapsed/refractory AL amyloidosis represent an unmet clinical need and novel targeted drugs require urgent prospective assessment.

Personnel Detection in Dark Aquatic Environments Based on Infrared Thermal Imaging Technology and an Improved YOLOv5s Model.

This study presents a novel method for the nighttime detection of waterborne individuals using an enhanced YOLOv5s algorithm tailored for infrared thermal imaging. To address the unique challenges of nighttime water rescue operations, we have constructed a specialized dataset comprising 5736 thermal images collected from diverse aquatic environments. This dataset was further expanded through synthetic image generation using CycleGAN and a newly developed color gamut transformation technique, which significantly improves the data variance and model training effectiveness. Furthermore, we integrated the Convolutional Block Attention Module (CBAM) at the end of the last encoder's feedforward network. This integration maximizes the utilization of channel and spatial information to capture more intricate details in the feature maps. To decrease the computational demands of the network while maintaining model accuracy, Ghost convolution was employed, thereby boosting the inference speed as much as possible. Additionally, we applied hyperparameter evolution to refine the training parameters. The improved algorithm achieved an average detection accuracy of 85.49% on our proprietary dataset, significantly outperforming its predecessor, with a prediction speed of 23.51 FPS. The experimental outcomes demonstrate the proposed solution's high recognition capabilities and robustness, fulfilling the demands of intelligent lifesaving missions.