Positive Response Research Articles

PENDAMPINGAN KELOMPOK USIA DINI (PAUD TERPADU FAST STAR) DALAM KEGIATAN PENANAMAN DI PANTAI SULI KABUPATEN MALUKU TENGAH

Early age group assistance (Fast Star Integrated PAUD) aims to motivate and shape children's character from an early age to love nature and preserve the environment. This mentoring and field practice approach while learning was chosen to provide knowledge, understanding and skills to students about the importance of a tree or plant for human life and the natural environment. The stages of implementing this activity include Seed Preparation, Land Preparation, Seedling Transportation, Socialization about the Importance of Trees for Life, and Planting. Students gave a positive response to the importance of trees for life by asking questions and answering questions given during socialization. In addition, the motivation given to the students aroused their enthusiasm to carry out planting at Suli Beach and around their respective homes.

Panel-reactive antibodies in kidney transplantation for patients with end-stage renal failure

BACKGROUND: Kidney transplantation is a recognized method of treating patients with end–stage kidney disease. However, the risk of graft loss is not excluded. In Azerbaijan, kidney transplantation is mainly performed from living donors; nevertheless, there is little data on the panel-reactive antibodies (PRA) and its use in the transplantation program. AIM: To evaluate the prevalence of positive panel-reactive antibodies (PRA) and short-term outcomes of living donor kidney transplantation. MATERIALS AND METHODS: Within 6 months after kidney transplantation, 113 recipients were followed up. All patients underwent their first transplantation. Complement-dependent cytotoxicity cross-matching, HLA typing, and flow cytometry cross-matching were carried out. Flow cytometric analysis was applied to detect PRA. The positive response percentage is presented by the percentage of events shifted to the right of the cutoff point. Data were analyzed using SPSS 16.0 statistical software. RESULTS: Among the examined patients, men predominated. In PRA-positive patients (n = 20), the dialysis duration was on average 22.3% longer than in PRA-negative patients (n = 93). 35.0% of PRA-positive patients had class I PRA, 30.0% of patients had class II PRA, and 35.0% had class I + II PRA. In 40.0% of cases, positive PRA had high sensitization 50% (predominantly class II), and the remaining 60.0% had PRA from 10% to 50%. Sensitizing factors were more common in the PRA-positive group (p 0.05). After 6 months of folow-up, the mean creatinine level was 183.4 ± 68.84 nmol/l in the PRA-positive group and 198.15 ± 108.23 nmol/l in the PRA-negative group (p = 0.91). The overall emptying rate was 4.4% (n = 5), with all 5 cases being in the PRA-negative group. No deaths were observed during the follow-up period. CONCLUSIONS: PRA positive patients usually have some sensitizing event such as pregnancy or blood transfusion. The transfusion itself was not a significant factor of sensitization in this study. Patients with high PRA levels require more thorough examination.

Identification of Two R2R3-MYB Genes Involved in Flavan-3-Ols Biosynthesis as Modulated by Salicylic Acid Through RNA-Seq in Grape Berries (Vitis spp.)

Flavan-3-ols are plant secondary metabolites that play important roles in stress resistance. Our previous studies revealed that salicylic acid (SA) activates R2R3-MYB transcription factors, promoting flavan-3-ol biosynthesis. This study identified two R2R3-MYB genes that exhibited positive responses to both exogenous SA and were probably involved in flavan-3-ol biosynthesis through RNA-sequencing, functional enrichment analysis, and qRT-PCR. The results indicated that the contents of total flavan-3-ols and their monomers, (+)-catechin and (−)-epicatechin, in grape berries after exogenous SA application were substantially increased compared to those in the control. A total of 683 differentially expressed genes in response to exogenous SA treatment were identified using RNA-seq. KEGG analysis revealed enrichment of the ‘flavonoid biosynthesis’ and ‘plant hormone signal transduction’ pathways. A specific module highly associated with flavan-3-ol biosynthesis was identified by constructing a co-expression network. Two candidate genes (VvMYB108B and VvMYB145) likely participating in flavan-3-ol biosynthesis were selected using qRT-PCR. Therefore, these two potential genes that respond to SA and putatively participate in flavan-3-ol biosynthesis were identified for the first time. These results lay a solid basis for a more profound understanding of the molecular regulation of flavan-3-ol biosynthesis in grapes.

Abstract B038: Establishing a screening platform to identify key signaling molecules regulating cold tumor formation through immune evasion and exclusion

Abstract Many trial data have shown that cancer immunotherapy can successfully induce long lasting anti-cancer immune responses and increased the survival rate of cancer patients. One of the key challenges facing cancer immunotherapy is the low response rate of cancer patients to immunotherapy, suggesting that these cancer patients may have acquired resistance toward immunotherapy before treatments. Therefore, there is an unmet need for identifying the underlying mechanisms that promote resistance. One important hypothesis is that immune-excluded tumors (so called cold tumors) that lack of functional T cells have been often found in cancer patients who cannot respond well to cancer immunotherapy. To address this, we have successfully established a preclinical model for cold lung tumors, conducted RNA-seq, performed hallmark gene set enrichment analysis (GSEA) on cold tumor cells sorted in vivo, and identified several candidates associated with epithelial-mesenchymal transition, Wnt signaling, type I and II interferon (IFN) signaling, and p53 signaling. We hypothesize that their roles may either promote or inhibit the formation of cold tumors. One of the molecular candidates we identified, a molecule designated as IRC001, represents a crucial proof of concept for our experimental tumor model. We have unveiled a novel role for IRC001 in enhancing anti-tumor immunity, leading to the transformation of cold tumors into hot tumors and facilitating swift tumor regression through pathways reliant on T cells and type I IFN signaling. Our mechanistic studies have shown that IRC001 can trigger type I IFN signaling by engaging STING/TBK-1/IRF3-dependent pathways. To delve deeper into the spatial and molecular distinctions in mouse tumors (± IRC001), we initiated a preliminary study utilizing 10x Genomics/Visium to examine the spatial variations between these tumor types. Significantly, our spatial transcriptomic analysis revealed consistent immune-excluded and immune-enriched characteristics compared to traditional RNA sequencing methods. We conducted an analysis of TCGA datasets (The Cancer Genome Atlas) and observed that elevated IRC001 expression is associated with improved prognosis in SKCM (Skin Cutaneous Melanoma). Furthermore, our bioinformatics analysis revealed that melanoma patients exhibiting heightened IRC001 expression displayed positive responses to immune checkpoint blockade therapies. Therefore, we believe that our experimental tumor model can provide vital insights into the cold tumor microenvironment, shaping future therapeutic strategies, and pinpointing molecular candidates that can assist in selecting patients for successful immunotherapy. Citation Format: Yi-Ting Liao, Li-Mei Chen, Wen-Jye Lin. Establishing a screening platform to identify key signaling molecules regulating cold tumor formation through immune evasion and exclusion [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B038.

Accuracy of full-guided versus half-guided implant procedures carried out with digital implant planning software by students as part of a university curriculum.

This in vitro study investigated whether full-guided (FG) or half-guided (HG) implant placement is more suitable for beginners and to what extent the use of the coDiagnostiX (CDX) (10.5, Straumann Group, Basel, Switzerland) implant planning software proves useful in teaching. Twenty students planned implant positions with CDX which were then placed in a model using printed drill templates in the sense of FG implantation (group 1) and HG implantation (group 2). The implant positions could be compared with those of the reference model, and deviations could be determined. The results were tested for significance using the t-test for independent samples for groups 1 and 2. A total of 32 students subsequently completed a questionnaire about the software. Cronbach's α was also calculated to check the reliability of the questions for the individual subject areas. In both groups the greatest deviation occurred along the y-axis in the vestibular direction. It measured 1.390mm in group 1 and 1.570mm in group 2. Comparing both groups, there were significant deviations along the y-axis (p = .013), along the z-axis (p = .049), and in the total deviation (p = .031). The questionnaire was evaluated in design, with 95% positive answers. In contrast, the evaluation of the area of time and effort resulted in only 55% positive responses. Overall, experience with the software was rated as positive by 74%. Group 1 achieved more accurate results, especially along the y-axis in the vestibular direction. In both groups, the implants were placed too deep. The questionnaire indicated a software with high usability and is therefore very suitable for teaching. If clinically feasible, beginners should prefer full-guided implant placement.

Penile constriction devices: a randomized survey study to compare preferences between two medical-grade devices.

Penile constriction devices offer a noninvasive approach to enhance the sexual experience and as the variety of penile constriction devices increases, it is crucial to assess patient preferences and device effectiveness to provide insights into their clinical utility. We aimed to compare the preferences for and effectiveness of two medical-grade penile constriction devices: Eddie by Giddy and FirmTech. Between May and July of 2023, males were recruited via social media and prospectively enrolled into an Institutional Review Board-approved, randomized, questionnaire-based study. Upon enrollment, the participants completed the Sexual Health Inventory for Men and Androgen Deficiency in Aging Males questionnaires. Participants were randomized to which device they received first. They used the device twice either during masturbation or intercourse in a two-week timeframe. Once utilized, the participants completed a 17-question, Likert scale, device satisfaction questionnaire, in which lower numbers indicated positive responses. The process was repeated with the second device. T-test and Chi-Square Analysis were run for statistical analysis. The primary outcomes of this study were patient-reported device satisfaction and efficacy and the secondary outcome was the device preference for patients with and without erectile dysfunction. Fifty men were enrolled and 49 completed the study. The average age was 40years old. Of the participants, 80% recommend the FirmTech device compared to 53% who recommend the Eddie by Giddy device (P= 0.0026). The FirmTech device was overall easier to put on both flaccid and erect (P= 0.0308 and 0.0002), was more comfortable, had better stretch, and was easier to adjust (P= 0.087, <0.0001, and 0.0119, respectively). The FirmTech device had a better overall impression amongst the participants (P= 0.0249). Eddie by Giddy was felt to improve erectile firmness more in those with ED than in those without (P = 0.0178). This study adds to the current literature on penile constriction devices that better guide providers as they counsel patients on these devices to enhance sexual function. The strength of this study is that this is a prospective randomized crossover study. The limitations of this study are that this is a single center study based on patient reported outcomes. The FirmTech device performed better than the Eddie by Giddy with respect to overall impression of the device, likelihood of using the device in the future, and recommending the device to a friend, while the Eddie by Giddy device performed better at improving erectile firmness. NCT05853822.

Research on the design and image perception of cultural landscapes based on digital roaming technology

AbstractThe preservation and advancement of cultural heritage continue to present significant challenges, arising from conflicting objectives, concepts, methodologies, and limited resources. Image perception not only serves as an observational tool for cultural heritage but also as a research method to uncover deeper meanings and implications. To explore the complex dynamics of cultural heritage and address the risks of its deterioration, this study employed virtual engine software (Unity 2019) to create digital landscapes for immersive exploration. An image perception evaluation framework was established through field surveys and behavioral synthesis experiments across five key areas, including ancient tree ecosystems and architectural sites. Our findings revealed that participants showed the greatest interest in the ancient tree ecological area, indicating a strong attachment to historical continuity and natural progression. Heart rate variability (HRV) analysis further demonstrated that participants experienced positive emotional responses, suggesting that well-designed cultural landscapes can enhance mental well-being and uplift mood. Additionally, participants expressed a strong willingness to discuss the ancient tree eco-region, with image perception playing a crucial role in motivating information sharing and driving conservation efforts. This study introduces an innovative model—Design Practice, Immersive Experience, and Image Perception Evaluation—which offers a new perspective for the preservation and enhancement of cultural heritage sites.

The Development of ChemicoMine, Maritime Chemistry Comic Webtoon as an Edutainment Media Accordance to the IMO Regulations

Based on the IMO Model Course 7.04 curriculum, chemistry is an introductory course that a candidate for sailor must master. However, most abstract chemistry concepts require technology-based learning media and edutainment. Webtoon is a digital comic that presents the concept of chemistry through real-life visualization strategies to attract student interest. This research aimed to create ChemicoMine, a maritime chemistry comic webtoon whose material content follows IMO regulations. The research method is R&amp;D with the ADDIE model, which is limited to the Development stage. The instruments used in this research were analyst instruments of necessity, the validation tools of storyboard, the instrument validated by an expert in media and material, and the instrument for students. The data analysis techniques used the Likert scale 5. Validation results from an expert in material and media stated that the product received a percentage rating of 87.66% and 95.28% with the category (very good). Student response results obtained percentage of rating of 88.94% with the category (very good). Based on the results, ChemicoMine received a positive student response and can be used as an alternative edutainment media.

Predictors of outcomes after gastric peroral endoscopic myotomy for refractory gastroparesis: a systematic review

Background: Gastroparesis is a debilitating gastroduodenal disorder for which gastric peroral endoscopic myotomy (GPOEM) has emerged as an efficacious treatment option. However, response to GPOEM varies between 50-80%, such that preoperative predictors of treatment success are needed to guide patient selection. Methods: We performed a systematic review to identify predictors of clinical and functional response to GPOEM among adult patients with gastroparesis (PROSPERO: CRD42023457359). MEDLINE, Embase, and CENTRAL databases were searched systematically for studies reporting outcomes after GPOEM in September 2023. A narrative synthesis of predictive factors on univariable and multivariable analysis was performed with consideration of response rates via meta-analysis, and evaluation of discrimination if prognostic models were developed. ROBINS-E was used for risk of bias assessment. Results: Of 1899 articles reviewed, 30 were included. The GPOEM response rate was 63.1% (95% confidence interval 56.3%-69.5%) with most studies defining clinical success on the basis of improvement in gastroparesis cardinal symptom index (87%, 26/30). Older age, shorter duration of gastroparesis, non-diabetic etiology, lower body mass index, and response to intrapyloric botulinum toxin were associated with positive response to GPOEM on multivariable analyses. Predictors on physiological tests such as EndoFLIP or gastric emptying scintigraphy were inconsistent. No prognostic models underwent external validation. Conclusion: Currently, there are limited reproducible predictors of response to GPOEM among patients with refractory gastroparesis. Robust prospective studies investigating scalable, reproducible, and actionable biomarkers of treatment response are required.

Erythema, localized edema and heat vs forearm perimeter increase. Time to revise the consensus recommendations on the vortex provocation test in vibratory urticaria-angioedema?

Diagnosis of vibratory urticaria/angioedema is established after performing the vortex provocation test. There is current consensus on measuring the forearm perimeter after running such test to define a positive response to it. We evaluated the frequency of prior symptoms following vibratory stimuli in volunteers using a questionnaire, response to the vortex provocation test in the same volunteers (increase in forearm perimeter, erythema, localized edema, heat, and pruritus), interrater reliability, and correlation between the scores obtained in the questionnaire and response to the test. A total of 40 volunteers participated in this survey, 17 of whom were excluded due to dermographism. A total of 59% out of 123 without dermographism responded positively to ≥ 1 items of the questionnaire. Localized erythema, heat or localized edema were reported in 58.5%, 38.2%, and 32.5%, respectively. A total of 73.6% of volunteers presented with itch. The mean intensity of itch was 3.44 (95%CI, 2.94-3.94). Interrater agreement was low regarding the increase in forearm circumference at 3 levels (intraclass correlation coefficient, 0.477 95%CI, 0.253-0.634; 0.496 95%CI, 0.280-0.647; and 0.370 95%CI, 0.100-0.559, respectively) and optimal regarding erythema, heat and localized edema (Kappa index, 0.868; .756; and .757, respectively). A significant correlation was identified between the questionnaire score and the altered response to the test in its different variables. We propose the following variables: erythema; localized edema; heat; and the intensity/speed of onset/duration of pruritus to define a positive response to the vortex provocation test given their ease of execution and optimal inter-observer agreement.

HPB SO44 - From Electives to Career-Changing: A Cross-Sectional Survey exploring the impact of International Medical Electives in Hepato-Pancreatic-Biliary Surgery Unit

Abstract Background International medical graduates (IMGs) are crucial in addressing NHS workforce shortages, representing one-third of staff. Reliance on IMGs is likely to continue. Electives offer IMGs a valuable opportunity to overcome work culture and clinical skills challenges, difficult to address through PLAB tests alone. These experiences can aid in passing the exam. Entering a new culture and service can be daunting; electives help build confidence by increasing familiarity with the NHS and UK medical traditions. This survey was designed to gain insight into IME experiences, the educational value perceived by participants, and their influence on personal growth and career direction. Method A cross-sectional survey was sent to 26 IMGs who completed an IME rotation in the HPB department at University Hospitals of Leicester NHS Trust since 2019. The survey included quantitative and qualitative questions to gather demographic details, insights into experiences, educational values gained, and career impact. Medical education and HPB surgery experts evaluated the survey for content validity and alignment with learning outcomes.Conducted via Google Forms®,recruitment emails were sent anonymously with weekly reminders for four weeks to ensure high response rates. Quantitative data were analysed using descriptive statistics, and qualitative data underwent thematic analysis. Results 18 out of 26 participants (62.2%) responded. Ages ranged from 23-30, with 61.11% between 23-25 years. The gender split was 61.11% male and 38.89% female. Most (66.67%) were medical students during their elective, while 33.33% were Foundation Doctors. 72% of respondents are preparing for or have taken GMC registration exams, with 44% are already fully registered. The survey revealed overall positive responses, highlighting the welcoming and educational environment. However, participants suggested improving the induction program and providing a more defined daily schedule for elective students. These insights offer opportunities to enhance an already valuable program. Conclusion The study revealed a successful international medical elective program in the HPB department. Most respondents found the experience met their expectations, achieved learning objectives, and positively influenced their careers. All participants were satisfied and would recommend the elective, with 94% considering NHS careers. The program provided effective teaching, mentorship, and hands-on clinical experience for most participants. Many have begun or completed GMC registration, indicating lasting impact. This initiative is valuable in attracting and preparing IMGs for the NHS and should be replicated across the UK, with a structured program and ensuring necessary exposure and guidance.

HYPERCONTENT DEVELOPMENT TRAINING FOR RICH AND RENEWABLE LEARNING RESOURCES AT STATE SENIOR HIGH SCHOOL 1 DRIYOREJO, GRESIK

This community service activity aims to provide Hypercontent Development Training for Rich and Renewable Learning Resources. at SMA Negeri 1 Driyorejo, Gresik as a good researcher for teachers. Specifically, this activity aims to Bind Interaction in Learning at SMA Negeri 1 Driyorejo, Gresik smoothly and in accordance with the even semester period of the 2023-2024 academic year. The methods used in this PPM activity include lectures or counseling containing the delivery of information for general and theoretical materials, in this case the material (1) Application of Hypercontent Development Training for Rich and Renewable Learning Resources, (2) Excavation Hypercontent Development Training for Rich and Renewable Learning Resources. The PPM activities that have been implemented have run smoothly in accordance with the expected goals of this program, and have obtained good results. The lecturers who presented received knowledge sharing on how to practice Hypercontent Development Training for Rich and Renewable Learning Resources at SMA Negeri 1 Driyorejo, Gresik. The high school teachers received additional knowledge about Hypercontent Development Training for Learning Resources. The Hypercontent Development Training Program for Learning Resources in addition to receiving positive responses from teachers of SMA Negeri 1 Driyorejo, Gresik, also received responses from supervisors in the Driyorejo District Education Office Branch, Gresik Regency. The training participants hope that the Hypercontent Development Training for Learning Resources can be continued in the future considering the benefits of this program. Furthermore, the institutional cooperation that has been well established between UNIPA Postgraduate School, especially the Department of Educational Technology with the Driyorejo District Education Office Branch, Gresik Regency is expected to continue in the future as part of the Tri Dharma of Higher Education.

ANALYSIS OF THE USE OF THE WORDWALL APPLICATION IN LEARNING ENGLISH USING CHROMEBOOK FOR VOCABULARY

This study aims to explore the subjective experiences, perceptions, and challenges faced by English teachers and students in implementing the WordWall application in their classroom environment, especially when used together with Chromebooks to learn vocabulary. The research method used is qualitative by collecting data through interviews, questionnaires and observation. The results of interviews with teachers showed that WordWall was assessed positively in increasing student engagement and vocabulary understanding, even though several technical challenges such as slow internet connections were encountered. Student questionnaires also yielded positive responses, with the majority of students feeling more engaged and their vocabulary understanding improved after using WordWall. Observation results indicate that WordWall in combination with Chromebooks is effective in creating an interactive learning environment that facilitates student engagement. In conclusion, using WordWall with Chromebooks can be an effective tool in enhancing English language learning in the classroom, by offering students an engaging and interactive learning experience.

Assessing Post-Vaccination Seroprevalence and Enhancing Strategies for Lumpy Skin Disease Vaccination in Korean Cattle

Lumpy skin disease (LSD), caused by the LSD virus (LSDV), a dsDNA virus of the genus Capripoxvirus, represents a significant cross-border infectious threat, particularly impacting cattle and water buffaloes through transmission by blood-feeding insects. Traditionally endemic to Southern Africa, LSD has rapidly spread over the past decade through the Middle East to Eastern Europe and China, reaching Korea in October 2023. This outbreak prompted a nationwide vaccination campaign, addressing both the disease’s severe economic impact and its status as a notifiable disease under the World Organisation for Animal Health. This study assesses the seropositivity of the LSD vaccine in cattle across four Korean provinces 2–3 months post-vaccination, aiming to inform improvements in biosecurity and vaccination strategies. Overall, 30.59% of the cattle tested (1196 out of 3910) exhibited positive antibody responses, comparable to international post-vaccination findings. Analysis further revealed differences in the antibody positivity between farm types and management practices. Specifically, farms where vaccines were administered by veterinarians showed no significant difference in antibody positivity between Korean native cattle and dairy cattle, regardless of the presence of restraint facilities. However, on farms where vaccinations were conducted by the owners, dairy cattle demonstrated a higher seropositivity (43.30 ± 33.39%) compared to Korean native cattle (21.97 ± 20.79%) in the absence of restraint facilities. Further comparisons underscored the impact of restraint facilities on vaccination efficacy, with dairy farms generally achieving higher antibody positivity (29.43 ± 30.61%) than farms with Korean native cattle (23.02 ± 23.33%) (p &lt; 0.05), suggesting that consistent vaccine delivery methods enhance immunogenic responses. Contrarily, no significant difference was noted in antibody positivity between large- and small-scale farms, indicating that farm size did not notably impact the effectiveness of the vaccinator. These findings emphasize that while current vaccines are sufficiently inducing immunity, enhancing vaccination strategies, particularly through trained personnel and improved restraint facilities, is crucial. This study’s insights into the impact of vaccination and farm management practices provide valuable guidance for refining LSD control measures in Korea and potentially other affected regions.

Young Bedouin-Arab Men’s Ego and Pride: Do Traditional Masculinity and Positive Attitudes Toward Polygyny Shape Responses to a Wife’s Refusal?

Cultural traditions in Israel’s Bedouin-Arab community encourage and permit men to take up to four wives, a practice supported by Islamic teachings. Despite legal prohibitions against polygyny in Israel, such marriages remain common and have profound effects on women, children, and broader society. This study explores how traditional notions of masculinity and positive attitudes toward polygyny influence young Bedouin men’s reactions to a hypothetical scenario in which their wife refuses to accept a polygynous marriage as a threat to men’s ego and pride. The sample consisted of 459 young, unmarried Israeli Bedouin-Arab men, aged 16 to 25, a demographic frequently under family pressure to marry, making the issue of marriage highly relevant. We hypothesized that traditional masculinity and favorable attitudes toward polygyny would be positively associated with heightened perceptions of ego and pride threats in response to a wife’s refusal. Participants were randomly assigned to imagine either their wife refusing a polygynous arrangement (n = 228) or accepting a polygynous arrangement (n = 231) and then reporting their anticipated emotional responses. The results showed that traditional masculinity was linked to positive attitudes toward polygyny, and both were significantly associated with increased perceptions of ego and pride threats in the refusal scenario but not in the acceptance scenario. The findings suggest that men with strong masculine identities and favorable views of polygyny are especially vulnerable to feeling threatened by a wife’s refusal. This supports social construction theory and underscores the role of cultural norms in shaping emotional responses. The discussion highlights the psychological impacts of polygyny in patriarchal societies and calls for culturally sensitive interventions that challenge traditional norms while fostering psychological resilience and gender equality.

Functional characterization of optic photoreception in Lymnaea stagnalis.

Optic photoreception is a critical function for animal survival. Across the evolutionary spectrum, diverse animal models have been used to investigate visual system function and potential mechanisms under physiological or pathophysiological states. However less is known on photoreceptive behaviors and retinal processing in invertebrates, especially molluscs. This study focuses on the freshwater pond snail, Lymnaea stagnalis (L. stagnalis), to explore its visual function and underlying mechanisms. Using anatomical and histological approaches we characterized the L. stagnalis eye structure and demonstrated structural connections and retinal rhodopsin-positive sensory cells potentially critical for phototransduction. To assess the snail phototactic responses, we developed a new neurobehavioral protocol and employed DeepLabCut to track and quantify animal locomotion. We demonstrated that L. stagnalis exhibits a positive locomotory response to intense focal light and has diverse photo-locomotory responses. Further, we conducted phylogenetic and protein structure analyses and demonstrated that L. stagnalis has a unique repertoire of both vertebrate and invertebrate phototransduction genes. Further characterization of a rhodopsin-like gene identified unique characteristics compared to other mollusks and vertebrates, suggesting different mechanisms of phototransduction. Taken together, our work establishes L. stagnalis as a model organism for studying optic photoreception, offering new insights into the evolution and diversity of visual function across animal species.

The Correlation Patterns of miRNA Expression with Targeted mRNA Transcripts in Glioma Patients with Wild-Type and Mutated Isocitrate Dehydrogenase (IDH) Genotypes.

Low-grade gliomas are divided into two main genetic phenotypes based on the presence or absence of mutations in the isocitrate dehydrogenase (IDH) genes. The mutated IDH phenotype (IDHmut), in contrast to the wild-type phenotype (IDHwt), is characterized by a more positive response to pharmacological intervention and a significantly longer survival time. In this study, we analyzed the differential co-expression of 225,000 microRNA-mRNA pairs at the level of correlations between microRNA levels and their potential mRNA targets. Analysis of the associative relationships of individual representatives of the selected pairs revealed that the level of mRNAs encoded by the ELN, ARL4C, C9orf64, PLAT, and FKBP9 genes associated with aggressive progression of glioma was increased in the IDHwt group. Meanwhile, the levels of miRNA-182, miRNA-455, and miRNA-891a associated with the negative prognosis in glioma were generally increased in the IDHmut group. Most (16/21) of the detected 21 microRNA-mRNA pairs with significant difference in regulation between IDHwt and IDHmut glioma samples had a weak or moderate positive correlation in IDHmut samples and a negative correlation in IDHwt samples. Therefore, our findings indicate that glioma samples from the IDHmut group with a positive prognosis potentially have a significantly less pronounced ability to microRNA-mediated regulation. We further suggest that such physiological disorders can lead to reduced tumor viability, resulting in an increased ability of the host to resist the spread of a malignant transformation of this genetic phenotype.

Tertiary Lymphoid Structures and Immunotherapy: Challenges and Opportunities.

Tertiary lymphoid structures (TLS)are accumulations of lymphoid cells that arise in ectopic sites through the process of lymphoid neogenesis in chronic inflammation in autoimmunity, microbial infections, organ rejection, aging, and cancer. Their cellular composition and function and regulation via members of the lymphotoxin (LT)/tumor necrosis factor (TNF) family resemble that of secondary lymphoid organs (SLOs). Tumor-associated (TA)-TLS can be associated with favorable clinical outcomes. Immunotherapy in the form of immune checkpoint inhibitors (ICI) has contributed to tremendous advances in cancer therapy. However, ICI are effective in only some tumors, can give rise to resistance, and can precipitate immune-related adverse events (irAEs), many of which appear to have hallmarks of autoimmunity and can resemble TLS. TA-TLS correlate with a positive response to immunotherapy, but they can also be associated with susceptibility to irAEs, suggesting that TA-TLS in combination with ICI could lead to uncontrolled autoimmunity. The tumor environment can be manipulated to ensure that, not only the number of TLS, but also their cellular composition and appropriate function allow for judicious combinations of TLS and immunotherapy that can synergize and contribute to better outcomes with a minimum of destructive irAEs. Strategies include directed delivery of lymphoneogenic cytokines and chemokines or vascular growth factors directly, via transgenes or via adenovirus vectors.

Advancement of Techniques for Precise Visualization and Quantification of Tertiary Lymphoid Structure-Associated Immune Cells in Tissue Samples.

Tertiary Lymphoid Structures (TLS) are considered as genuine markers of inflammation. Their presence within inflamed tissues or the tumor microenvironment has been associated with the local development of an active immune response. While high densities of TLS are correlated with disease severity in autoimmune diseases or during graft rejection, it has been associated with longer patient survival in many cancer types and more recently with positive responses to anti-PD-1 immunotherapy. Their efficient visualization and quantification within human tissues may represent new tools for helping clinicians in adjusting their therapeutic strategy. In clinical settings, the use of single-marker immunohistochemistry (IHC) protocols prevails in immune cell infiltration in formalin-fixed, paraffin-embedded (FFPE) tissues. In contrast, the development of automated multiplex immunofluorescence markings, i.e., 40-plex, requires very costly investments in equipment and analysis stations. Yet, employing two or more markers can enhance the characterization of immune infiltrates, particularly in the context of TLS. Besides the growing development of multiplex labeling approaches, imaging can also be used to overcome some technical difficulties encountered during the immunolabeling of tissues with several markers.This chapter describes IHC methods to visualize in human tissue (tumoral or not) the presence of TLS. These methods are based on the immunostaining of four TLS-associated immune cell populations, namely, follicular B cells, follicular dendritic Cells (FDCs), mature Dendritic Cells (mDCs), and Follicular Helper T cells (TFH), together with non-TFH T cells. Methodologies for subsequent quantification of TLS density are also proposed, as well as a virtual multiplexing method based on image registration using the open-source software ImageJ (IJ), aiming at co-localizing several immune cell populations from different IHC stainings performed on serial tissue sections.

DBS in the treatment of Parkinson’s disease

Purpose of the Study: This review examines the role of Deep Brain Stimulation (DBS) as a therapeutic intervention for advanced PD, focusing on indications, patient selection criteria, and potential complications. Materials and Methods: A comprehensive literature review was conducted, analyzing 37 studies from the PubMed database (English-language, up to October 2024) that assess the efficacy, safety, and long-term outcomes of DBS in managing advanced PD symptoms. Basic results: DBS has proven effective in enhancing motor function and quality of life in advanced PD cases. Although generally safe, DBS can present risks, including infections, dyskinesia, and psychiatric side effects. Conclusions: DBS is well known and constantly improving technology. Appropriate patient selection is essential; DBS is generally reserved for patients meeting specific criteria, including a confirmed PD diagnosis, disease duration of more than four years, a positive response to levodopa, and the absence of severe cognitive or unmanaged psychiatric disorders. Emerging research on genetic factors may enhance patient selection in the future.