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Abstract This study was aimed at introducing a new method for predicting the original metrics of fragmented standardized artifacts, specifically of flint blades from the Middle Pre-Pottery Neolithic B (10,200/100–9,500/400 cal B.P.) in the Southern Levant. The excessive re-use of these artifacts or poor preservation conditions often prevent a complete set of metric data from being obtained. Our suggested approach is based on readily accessible machine learning (artificial intelligence) and neural network analysis. These are performed in a multi-paradigm programming language and numeric computing environment, with parameters represented by a rapid measurement system based on the technological features shared by all lithic artifacts of the studied assemblages. This method can be applied to various chronologies and/or contexts. A full set of metric data, including potential typological and functional elements of the assemblages studied, may provide a better understanding of the lithic technology involved; highlight cultural aspects related to the chaîne opératoire of the studied lithic production; and address issues related to cultural sub-divisions in larger-scale applications. Herein, neural network analysis was performed on blade samples from Middle Pre-Pottery Neolithic B sites from the Southern Levant specifically Nahal Yarmuth 38, Motza, Yiftahel, and Nahal Reuel.

Infertility, affecting one in six couples, is often related to the male partner’s congenital and/or environmental conditions or complications postsurgery. This retrospective study examines the link between orchiopexy for undescended testicles (UDT) and testicular torsion (TT) in childhood and adult fertility as assessed through sperm analysis. The study involved the analysis of semen samples from 7743 patients collected at Soroka University Medical Center (Beer Sheva, Israel) between January 2009 and December 2017. Patients were classified into two groups based on sperm concentration: those with concentrations below 5 × 106 sperm per ml (AS group) and those above (MN group). Medical records and surgical histories were reviewed, categorizing orchiopexies by surgical approach. Among 140 individuals who had undergone pediatric surgery, 83 (59.3%) were placed in the MN group and 57 (40.7%) in the AS group. A higher likelihood of being in the MN group was observed in Jewish compared to Arab patients (75.9% vs 24.1%, P = 0.006). In cases of childhood UDT, 45 (78.9%) patients exhibited sperm concentrations below 5 × 106 sperm per ml (P < 0.001), and 66 (76.7%) had undergone unilateral and 18 (20.9%) bilateral orchiopexy. Bilateral orchiopexy was significantly associated with lower sperm concentration, total motility, and progressive motility than unilateral cases (P = 0.014, P = 0.001, and P = 0.031, respectively). Multivariate analysis identified UDT as a weak risk factor for low sperm concentration (odds ratio [OR]: 2.712, P = 0.078), with bilateral UDT further increasing this risk (OR: 6.314, P = 0.012). Jewish ethnicity and TT diagnosis were associated with a reduced risk of sperm concentrations below 5 × 106 sperm per ml. The findings indicate that initial diagnosis, surgical approach, and ethnicity markedly influence male fertility outcomes following pediatric orchiopexy.

Restoration supports the recovery of ecological attributes such as cover, complexity, and diversity to slow the areal decline of natural ecosystems. Restoration activity is intensifying worldwide to combat persistent stressors that are driving global declines to the extent and resilience of coral reefs. However, restoration is disputed as a meaningful aid to reef ecological recovery, often as an expensive distraction to addressing the root causes of reef loss. We contend this dispute partly stems from inferences drawn from small-scale experimental restoration outcomes amplified by misconceptions around cost-based reasoning. Alongside aggressive emissions reductions, we advocate urgent investment in coral reef ecosystem restoration as part of the management toolbox to combat the destruction of reefs as we know them within decades.

There has recently been a growing effort to understand the physics and intricate dynamics of many-body and many-state (multimode) interacting bosonic systems in a comprehensive manner. For instance, in photonics, nonlinear multimode fibers are being intensely investigated nowadays due to their promise for ultrahigh-bandwidth and high-power capabilities. Similar prospects are being pursued in connection with magnon Bose-Einstein (BE) condensates, and ultracold atoms in periodic lattices for room-temperature quantum devices and quantum computation, respectively. While it is practically impossible to monitor the phase space of such complex systems (classically or quantum mechanically), thermodynamics has succeeded in predicting their thermal state: the Rayleigh-Jeans (RJ) distribution for classical fields and the BE distribution for quantum systems. These distributions are monotonic and promote either the ground state or the most excited mode. Here, we demonstrate the possibility to advance the participation of other modes in the thermal state of bosonic oligomers. The resulting nonmonotonic modal occupancies are described by a microcanonical treatment, while they deviate drastically from the RJ/BE predictions of canonical and grand-canonical ensembles. Our results provide a paradigm of ensemble equivalence violation and can be used for designing the shape of thermal states.

Chronic inflammation and oxidative stress can contribute to the development of cardiovascular diseases. Isoproterenol (ISO), a synthetic catecholamine, is used to study the effects of drugs on cardiotoxicity. Agmatine (AGM) is a type of biogenic amine produced through the decarboxylation of arginine. The purpose of the current study was to evaluate the effects of AGM against ISO-induced cardiotoxicity due to the described roles of AGM in cardiovascular disease. Four groups of thirty-two Wistar Albino rats were divided equally as control, ISO, AGM+ISO, and ISO+AGM. ISO was administered intraperitoneally (i.p.) twice at a dose of 150 mg/kg, at 24-hour intervals. Prior to and after ISO injection, 20 mg/kg of AGM was injected i.p. Hemodynamic measurements and serum and tissue biochemical analyses were evaluated at the end of the experiment. The levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) in the tissue were measured. In the ISO group, levels of lactate dehydrogenase (LDH) and creatine kinase (CK) were increased significantly (p [Med-Science 2023; 12(4.000): 1290-6]

Ovarian torsion is a gynecological emergency characterized by ovarian ischemic damage. This study aimed to investigate the possible protective effects of dexpanthenol (DEX)-an antioxidant molecule-against ovarian ischemic damage in rats. The rats were simple randomly grouped into (1) Sham group (n=8); (2) Ischemia (I) group (n=8) (2 hours of I in ovaries); (3) DEX+I group (n=8) (500 mg/kg DEX administration 30 minutes before 2 hours of I.) The removed ovaries were examined histopathologically and biochemically. In the DEX+I group, necrosis-pycnosis severity was significantly reduced compared to the I group; but congestion-hemorrhage severity was similar. In the I group, malondialdehyde (MDA) and total oxidant status (TOS) levels were slightly increased, and glutathione (GSH) levels were significantly decreased compared to the Sham group. In the DEX+I group, MDA and TOS levels were slightly reduced and GSH levels were slightly increased compared to the I group. DEX prevents ischemic damage in rat ovaries via an antioxidant effect. Further research is needed to support our findings. [Med-Science 2023; 12(4.000): 1213-7]

Abstract The ability of marine bacteria to direct their movement in response to chemical gradients influences inter-species interactions, nutrient turnover, and ecosystem productivity. While many bacteria are chemotactic towards small metabolites, marine organic matter is predominantly composed of large molecules and polymers. Yet, the signalling role of these large molecules is largely unknown. Using in situ and laboratory-based chemotaxis assays, we show that marine bacteria are strongly attracted to the abundant algal polysaccharides laminarin and alginate. Unexpectedly, these polysaccharides elicited stronger chemoattraction than their oligo- and monosaccharide constituents. Furthermore, chemotaxis towards laminarin was strongly enhanced by dimethylsulfoniopropionate (DMSP), another ubiquitous algal-derived metabolite. Our results indicate that DMSP acts as a methyl donor for marine bacteria, increasing their gradient detection capacity and facilitating their access to polysaccharide patches. We demonstrate that marine bacteria are capable of strong chemotaxis towards large soluble polysaccharides and uncover a new ecological role for DMSP in enhancing this attraction. These navigation behaviours may contribute to the rapid turnover of polymers in the ocean, with important consequences for marine carbon cycling.

Background/Objectives: Despite novel biological agents, steroid-dependent or -refractory graft-versus-host disease (GvHD) remains a severe complication of allogeneic hematopoietic cell transplantation (allo-HCT). Extracorporeal photopheresis (ECP) is an alternative, non-immunosuppressive treatment for patients with acute (aGvHD) or chronic (cGvHD) GvHD. The aim of this study was to investigate the safety and efficacy of ECP in the treatment of acute and chronic GvHD; Methods: We prospectively studied 112 patients with cGvHD who received one or more previous lines of treatment and 28 patients with steroid-dependent or refractory grade II-IV aGvHD post-alloHSCT. Results: In terms of severe aGvHD, most of the patients (19/28) responded to ECP treatment, while the five-year overall survival (OS) was 34%. After adjustment for several confounder factors, the reduction in immunosuppression (p = 0.026) and number of ECP sessions (p < 0.001) were associated with improved OS. Regarding chronic GvHD, only 19 patients failed to respond to ECP treatment; though significantly lower rates of response were presented in patients with visceral involvement (p = 0.037) and earlier post-transplant GVHD diagnosis (p = 0.001). Over a follow-up period of 45.2 [interquartile range (IQR): 5.6–345.1] months, the 5-year cumulative incidence (CI) of cGvHD-related mortality was 21.2% and was significantly reduced in patients with ECP response (p < 0.001), while the 5-year OS was 65.3%. Conclusions: Our results confirm the safety and efficacy of ECP in patients with GvHD and provide sufficient data for further investigation and the best combination drugs needed such that GvHD will not be the major barrier of allo-HCT in the near future.

We aimed to investigate the potential benefits of two doses of ivabradine (IVA)-an If sodium channel blocker against isoproterenol (ISO)-induced myocardial damage in rats.The rats were randomly divided into 4 groups: Control group (n=8); Saline was administered, ISO group (n=12); 150 mg/kg ISO was administered for 2 days, ISO+IVA (1 mg/kg) group (n=12); 1 mg/kg IVA was administered for 4 days in addition to ISO. ISO+IVA (10 mg/kg) group (n=12): 10 mg/kg IVA was administered for 4 days in addition to ISO. Thereafter, hemodynamic, histopathological, and biochemical studies were performed. In the ISO+IVA (1 mg/kg) and ISO+IVA (10 mg/kg) groups, ISO-induced myocardial changes including an increase in density of granulation tissue and degenerated cardiomyocyte were equally decreased. HR was mildly reduced, and arterial blood pressures were slightly increased in the IVA-treated groups versus the ISO group. In the hearts of IVA-treated groups, malondialdehyde (MDA) levels were significantly reduced and glutathione (GSH) level and catalase (CAT) activity were mildly increased compared to the ISO group. Elevation of GSH and CAT activity were more pronounced in the ISO+IVA (10 mg/kg) group. Our results indicate that both 1 mg/kg and 10 mg/kg doses of IVA are effective against heart damage induced by ISO via its negative chronotropic, anti-oxidant (dose-dependent), anti-inflammatory and anti-degenerative properties. [Med-Science 2023; 12(3.000): 667-73]

Abstract Blastocyst selection is primarily based on morphological scoring systems and morphokinetic data. These methods involve subjective grading and time-consuming techniques. Artificial intelligence allows for objective and quick blastocyst selection. In this study, 608 blastocysts were selected for transfer using morphokinetics and Gardner criteria. Retrospectively, morphometric parameters of blastocyst size, inner cell mass (ICM) size, ICM-to-blastocyst size ratio, and ICM shape were automatically measured by a semantic segmentation neural network model. The model was trained on 1506 videos with 102 videos for validation with no overlap between the ICM and trophectoderm models. Univariable logistic analysis found blastocyst size and ICM-to-blastocyst size ratio to be significantly associated with implantation potential. Multivariable regression analysis, adjusted for woman age, found blastocyst size to be significantly associated with implantation potential. The odds of implantation increased by 1.74 for embryos with a blastocyst size greater than the mean (147 ± 19.1 μm). The performance of the algorithm was represented by an area under the curve of 0.70 (p

Abstract Learning classification tasks of $$({2}^{n}\times {2}^{n})$$ ( 2 n × 2 n ) inputs typically consist of $$\le n(2\times 2$$ ≤ n ( 2 × 2 ) max-pooling (MP) operators along the entire feedforward deep architecture. Here we show, using the CIFAR-10 database, that pooling decisions adjacent to the last convolutional layer significantly enhance accuracies. In particular, average accuracies of the advanced-VGG with $$m$$ m layers (A-VGGm) architectures are 0.936, 0.940, 0.954, 0.955, and 0.955 for m = 6, 8, 14, 13, and 16, respectively. The results indicate A-VGG8’s accuracy is superior to VGG16’s, and that the accuracies of A-VGG13 and A-VGG16 are equal, and comparable to that of Wide-ResNet16. In addition, replacing the three fully connected (FC) layers with one FC layer, A-VGG6 and A-VGG14, or with several linear activation FC layers, yielded similar accuracies. These significantly enhanced accuracies stem from training the most influential input–output routes, in comparison to the inferior routes selected following multiple MP decisions along the deep architecture. In addition, accuracies are sensitive to the order of the non-commutative MP and average pooling operators adjacent to the output layer, varying the number and location of training routes. The results call for the reexamination of previously proposed deep architectures and their accuracies by utilizing the proposed pooling strategy adjacent to the output layer.

Abstract Cancer somatic mutations are the product of multiple mutational and repair processes, some of which are tightly associated with DNA replication. Mutation rates (MR) are known to be higher in late replication timing (RT) regions, but different processes can affect this association. Systematic analysis of the mutational landscape of 2787 tumors from 32 tumor types revealed that approximately one third of the tumor samples show weak association between replication timing and mutation rate. Further analyses revealed that those samples have unique mutational signatures and are enriched with mutations in genes involved in DNA replication, DNA repair and chromatin structure. Surprisingly, analysis of differentially expressed genes between weak and strong RT-MR association groups revealed that tumors with weak association are enriched with genes associated with cell–cell communication and the immune system, suggesting a non-autonomous response to DNA damage.

Atypical antidepressant mirtazapine (MIR) is primarily used to treat major depressive disorder. It has not been clarified whether cardiovascular uncertainties and mechanisms of action emerge as problems during the use of mirtazapine. Cisplatin (CIS) is an effective anti-cancer medication used to treat a variety of human malignancies. There were four groups of 32 Wistar albino male rats in all. Rats were split into 4 groups at random. 1. Control Group, 2. CIS Group, 3. MIR Group, 4. MIR+CIS Group. On the 15th day of the study, ECG, heart rate, and blood pressure were determined. Histopathological and biochemical analyses were carried out on cardiac and vascular tissue samples. Comparing the CIS group to the other groups, blood pressure was considerably lower in the CIS group (p [Med-Science 2023; 12(2.000): 579-86]

Abstract The Tara Pacific expedition (2016–2018) sampled coral ecosystems around 32 islands in the Pacific Ocean and the ocean surface waters at 249 locations, resulting in the collection of nearly 58 000 samples. The expedition was designed to systematically study warm-water coral reefs and included the collection of corals, fish, plankton, and seawater samples for advanced biogeochemical, molecular, and imaging analysis. Here we provide a complete description of the sampling methodology, and we explain how to explore and access the different datasets generated by the expedition. Environmental context data were obtained from taxonomic registries, gazetteers, almanacs, climatologies, operational biogeochemical models, and satellite observations. The quality of the different environmental measures has been validated not only by various quality control steps, but also through a global analysis allowing the comparison with known environmental large-scale structures. Such publicly released datasets open the perspective to address a wide range of scientific questions.

Traumatic brain injury (TBI) is a major health problem that affects millions of persons worldwide every year among all age groups, mainly young children, and elderly persons. It is the leading cause of death for children under the age of 16 and is highly correlated with a variety of neuronal disorders, such as epilepsy, and neurodegenerative disease, such as Alzheimer's disease or amyotrophic lateral sclerosis. Over the past few decades, our comprehension of the molecular pathway of TBI has improved, yet despite being a major public health issue, there is currently no U.S. Food and Drug Administration?approved treatment for TBI, and a gap remains between these advances and their application to the clinical treatment of TBI. One of the major hurdles for pushing TBI research forward is the accessibility of TBI models and tools. Most of the TBI models require costume-made, complex, and expensive equipment, which often requires special knowledge to operate. In this study, we present a modular, three-dimensional printed TBI induction device, which induces, by the pulse of a pressure shock, a TBI-like injury on any standard cell-culture tool. Moreover, we demonstrate that our device can be used on multiple systems and cell types and can induce repetitive TBIs, which is very common in clinical TBI. Further, we demonstrate that our platform can recapitulate the hallmarks of TBI, which include cell death, decrease in neuronal functionality, axonal swelling (for neurons), and increase permeability (for endothelium). In addition, in view of the continued discussion on the need, benefits, and ethics of the use of animals in scientific research, this in vitro, high-throughput platform will make TBI research more accessible to other labs that prefer to avoid the use of animals yet are interested in this field. We believe that this will enable us to push the field forward and facilitate/accelerate the availability of novel treatments.

The retina, a tissue of the central nervous system, is vital for vision as its photoreceptors capture light and transform it into electrical signals, which are further processed before they are sent to the brain to be interpreted as images. The retina is unique in that it is continuously exposed to light and has the highest metabolic rate and demand for energy amongst all the tissues in the body. Consequently, the retina is very susceptible to oxidative stress. VDAC, a pore in the outer membrane of mitochondria, shuttles metabolites between mitochondria and the cytosol and normally protects cells from oxidative damage, but when a cell’s integrity is greatly compromised it initiates cell death. There are three isoforms of VDAC, and existing evidence indicates that all three are expressed in the retina. However, their precise localization and function in each cell type is unknown. It appears that most retinal cells express substantial amounts of VDAC2 and VDAC3, presumably to protect them from oxidative stress. Photoreceptors express VDAC2, HK2, and PKM2—key proteins in the Warburg pathway that also protect these cells. Consistent with its role in initiating cell death, VDAC is overexpressed in the retinal degenerative diseases retinitis pigmentosa, age related macular degeneration (AMD), and glaucoma. Treatment with antioxidants or inhibiting VDAC oligomerization reduced its expression and improved cell survival. Thus, VDAC may be a promising therapeutic candidate for the treatment of these diseases.

Aim:Carbon tetrachloride (CCI4) is a volatile organic chemical agent that can cause damage to many tissues. Caffeic acid phenethyl ester (CAPE), which is structurally similar to flavonoids, is an active component of honeybee propolis. CAPE is known for its antitoxic, antioxidant, and anti-inflammatory effects. In this study, we aimed to investigate the effects of CAPE against testicular damage caused by CCI4.Materials and Methods:Twenty-eight Wistar albino rats were divided into 4 groups (n=7) as, Group 1: control (5% ethanol, 1 mL/day/ip), Group 2: olive oil (0.5 mL/day over/ip), Group 3: CCI4 (0.5 mL/kg over/ip), Group 4: CCI4+CAPE (10 μmol/kg/day/ip). Tissue samples collected at the end of the experiment were detected in 10% formaldehyde and embedded in paraffin. Five-micron-thick sections taken from paraffin blocks were stained with hematoxylin-eosin. To evaluate testicular damage, 100 tubules from each section were randomly examined at 20x magnification under a light microscope and classified as intact, atrophic, and degenerated tubules. Sections were examined by using Leica DFC 280 light microscope and Leica Q Win Image Analysis system (Leica Micros Imaging Solutions Ltd. Cambridge, UK).Results:The testicular sections of the control group and the olive oil group had a normal histological appearance. In the CCI4 group, 55.00±4.22% of the seminiferous tubules were intact, 25.00±2.67% were atrophic and 20.00±1.88% were degenerative. In addition, multinucleated giant cells were found in the lumen of some seminiferous tubules. In the CCI4+CAPE group, 72.14±3.91% of the tubules were intact, 16.42±2.10% were atrophic, and 11.42±2.36% were degenerative. While the number of affected tubules significantly increased in the CCI4 group compared to the control group (p

Algal blooms are hotspots of marine primary production that play central roles in microbial ecology and global elemental cycling. Here, the authors show how bloom termination by viral infection can shift the balance between eukaryotic and prokaryotic recyclers of phytoplankton biomass.

Abstract Background Alzheimer's disease (AD) exhibits mitochondrial dysfunctions associated with dysregulated metabolism, brain inflammation, synaptic loss, and neuronal cell death. As a key protein serving as the mitochondrial gatekeeper, the voltage-dependent anion channel-1 (VDAC1) that controls metabolism and Ca2+ homeostasis is positioned at a convergence point for various cell survival and death signals. Here, we targeted VDAC1 with VBIT-4, a newly developed inhibitor of VDAC1 that prevents its pro-apoptotic activity, and mitochondria dysfunction. Methods To address the multiple pathways involved in AD, neuronal cultures and a 5 × FAD mouse model of AD were treated with VBIT-4. We addressed multiple topics related to the disease and its molecular mechanisms using immunoblotting, immunofluorescence, q-RT-PCR, 3-D structural analysis and several behavioral tests. Results In neuronal cultures, amyloid-beta (Aβ)-induced VDAC1 and p53 overexpression and apoptotic cell death were prevented by VBIT-4. Using an AD-like 5 × FAD mouse model, we showed that VDAC1 was overexpressed in neurons surrounding Aβ plaques, but not in astrocytes and microglia, and this was associated with neuronal cell death. VBIT-4 prevented the associated pathophysiological changes including neuronal cell death, neuroinflammation, and neuro-metabolic dysfunctions. VBIT-4 also switched astrocytes and microglia from being pro-inflammatory/neurotoxic to neuroprotective phenotype. Moreover, VBIT-4 prevented cognitive decline in the 5 × FAD mice as evaluated using several behavioral assessments of cognitive function. Interestingly, VBIT-4 protected against AD pathology, with no significant change in phosphorylated Tau and only a slight decrease in Aβ-plaque load. Conclusions The study suggests that mitochondrial dysfunction with its gatekeeper VDAC1 is a promising target for AD therapeutic intervention, and VBIT-4 is a promising drug candidate for AD treatment.

Abstract Background A growing body of research demonstrates that economic conditions and racial and ethnic disparities result in excessive overuse of emergency departments (EDs) by a small group of socioeconomically marginalized residents. Knowledge and understanding of these issues on the part of the healthcare team can promote equality by providing structurally competent care. This study aims to identify the major social and structural factors related to patterns of ED visits by Arab and Jewish patients in Israel, where access to health services is covered by universal national health insurance. Methods A cross-sectional study was conducted using questionnaires of ED patients in a tertiary care medical center in Jerusalem. The hospital is the largest of the three EDs in Jerusalem with over 90,000 adult patient visits a year. The sample was stratified by ethnicity, including 257 Jewish patients and 170 Arab patients. The outcome variable was repeat visits for the same reason to the ED within 30 days. Results There were differences between Jewish and Arab patients’ social and structural characteristics, including health status, socioeconomic status, feeling of safety, and social support. There were also significant differences in some of the characteristics of health service utilization patterns, including ED repeat visits, language barriers when seeking healthcare in the community, and seeking information about medical rights. The variables associated with repeat visits were different between the two groups: among the Arab patients, repeat visits to the ED were associated with concerns about personal safety, whereas among the Jewish patients, they were associated with poverty. Conclusion The study illustrates the gaps that exist between the Arab and Jewish population in Israel. The findings demonstrated significant differences between populations in both health status and access to health services. In addition, an association was found in each ethnic group between different structural factors and repeat ED requests. This study supports previous theories and findings of the relationship between structural and social factors and patterns of health services utilization.

Abstract Use of artificial at night (ALAN) exposes the world to continuously increasing levels and distribution of light pollution. Our understanding of the adverse effects of ALAN is based mostly on observational or laboratory studies, and its effects are probably underestimated. Demonstration of direct experimental fitness consequences of ALAN on mammals is missing. We studied the effects of chronic light pollution at different wavelengths on fitness and glucocorticoid hormone levels under semi-natural conditions in two closely related species: the nocturnal common spiny mouse (Acomys cahirinus) and the diurnal golden spiny mouse (Acomys russatus). Our results clearly demonstrate the adverse effects of ALAN exposure on the fitness of both nocturnal and diurnal species, manifested by changes in cortisol levels and reproductive timing, reduced reproductive output and reduced survival, which differed between species and wavelengths. In A. russatus exposure to blue ALAN had the strongest effect on fitness, followed by white and yellow ALAN exposure. In A. cahirinus the results are more complex and suggest it suffered from the combined effects of ALAN and competition. Our research shows that light pollution presents a real threat to both nocturnal and diurnal species, affecting the species fitness directly and through interspecific interactions. Worryingly, these effects are probably not limited to spiny mice. The clear adverse effects we documented, as well as the differences between wave lengths, contribute to our ability to present science-based recommendations to decision makers regarding the use of artificial light at night. Such information and guidelines are highly important nowadays when lighting systems are being replaced to promote energy efficiency.

Recent transcriptomic-based analysis of diffuse large B cell lymphoma (DLBCL) has highlighted the clinical relevance of LN fibroblast and tumor-infiltrating lymphocyte (TIL) signatures within the tumor microenvironment (TME). However, the immunomodulatory role of fibroblasts in lymphoma remains unclear. Here, by studying human and mouse DLBCL-LNs, we identified the presence of an aberrantly remodeled fibroblastic reticular cell (FRC) network expressing elevated fibroblast-activated protein (FAP). RNA-Seq analyses revealed that exposure to DLBCL reprogrammed key immunoregulatory pathways in FRCs, including a switch from homeostatic to inflammatory chemokine expression and elevated antigen-presentation molecules. Functional assays showed that DLBCL-activated FRCs (DLBCL-FRCs) hindered optimal TIL and chimeric antigen receptor (CAR) T cell migration. Moreover, DLBCL-FRCs inhibited CD8+ TIL cytotoxicity in an antigen-specific manner. Notably, the interrogation of patient LNs with imaging mass cytometry identified distinct environments differing in their CD8+ TIL-FRC composition and spatial organization that associated with survival outcomes. We further demonstrated the potential to target inhibitory FRCs to rejuvenate interacting TILs. Cotreating organotypic cultures with FAP-targeted immunostimulatory drugs and a bispecific antibody (glofitamab) augmented antilymphoma TIL cytotoxicity. Our study reveals an immunosuppressive role of FRCs in DLBCL, with implications for immune evasion, disease pathogenesis, and optimizing immunotherapy for patients.

This retrospective study evaluates the effectiveness of combining 0.05% atropine with MF60 contact lenses in managing rapid myopia progression in children over one year. The study involved three groups: the treatment group (TG) with 15 children (53% male, average age 12.9 ± 1.04), the MF group (MF) with 12 children (50% male, average age 12.8 ± 0.8) using only MF60 lenses, and the control group (CG) with 14 children (43% male, average age 12.1 ± 0.76). Baseline myopia and axial length (AL) were similar across groups, with the TG, MF, and CG showing −4.02 ± 0.70 D, −4.18 ± 0.89 D, −3.86 ± 0.99 D, and 24.72 ± 0.73 mm, 24.98 ± 0.70 mm, 24.59 ± 1.02 mm, respectively. Prior to the study, all groups exhibited significant myopia and AL progression, with no previous myopia control management. The treatment involved daily 0.05% atropine instillation, the use of MF60 lenses and increased outdoor activity. Biannual cycloplegic refraction and slit lamp evaluations confirmed no adverse reactions. After one year, the TG showed a significant reduction in myopia and AL progression (−0.43 ± 0.46 D, p < 0.01; 0.22 ± 0.23 mm, p < 0.01), whereas the CG showed minimal change (−1.30 ± 0.43 D, p = 0.36; 0.65 ± 0.35 mm, p = 0.533). The MF group also exhibited a notable decrease (−0.74 ± 0.45 D, p < 0.01; 0.36 ± 0.23 mm). Increased outdoor activity during the treatment year did not significantly impact myopia control, suggesting its limited additional effect in this cohort. The study concludes that the combination of 0.05% atropine and peripheral defocus soft contact lenses effectively controls myopia progression in children.