Recipients of uterus transplantation have unique factors that may increase their risk of cervical insufficiency. This report describes a uterus transplant recipient with cervical insufficiency resulting in two second-trimester miscarriages. After McDonald cerclages (one that failed), she underwent an interval transabdominal cerclage and delivered a healthy term child in her third pregnancy. The longitudinal information of this case provides observations from which we can propose testable hypotheses that address venous outflow and inflammation. This case also suggests that there could be a role for prophylactic cerclage placement at the time of transplantation.

Chronic lymphocytic leukemia (CLL) is a distinct category of lymphoproliferative disorder characterized by the clonal expansion of mature B cells, followed by their accumulation in primary and secondary lymphoid organs. Cluster of differentiation (CD) markers such as CD20, CD22, CD23, CD5, and CD81 serve as reliable prognostic indicators and disease progression factors in CLL. The human leukocyte antigen (HLA) system is a critical genetic variable in many diseases, with well-documented associations between HLA and various cancers. This study aims to investigate, for the first time, potential connections between HLA typing and CD marker expression in CLL. Despite being one of the most prevalent neoplasms in developed regions, there is a need for biomarkers that can improve survival predictions and identify possible genetic determinants. Methods: This study included 66 CLL patients and 100 controls, with all samples analyzed using biochemical methods, flow cytometry, and cytomorphology. Next-generation sequencing (NGS) was performed for HLA typing. Results: The results indicate that several CD markers are statistically associated with different HLA alleles. Specifically, CD20 was associated with HLA-DRB1*11:04:01; CD45 with HLA-C*07:01:01; CD79b with HLA-DPA1*02:01:02; CD23 with HLA-B*39:01:01; CD43 with HLA-DRB1*15:01:01; CD22 with HLA-B*49:01:01, HLA-C*07:01:01, HLA-DPB1*02:01:02, and HLA-DRB1*07:01:01; and CD81 with HLA-DPB1*04:02:01, HLA-DQA1*01:04:01, and HLA-DQB1*05:03:01.Conclusion: In conclusion, this research demonstrates significant statistical links between HLA genes and immunophenotypic markers in CLL patients, shedding new light on the immunological context of CLL.

In the world's first pig-to-human cardiac xenotransplant, the elevated levels of porcine cytomeg-alovirus (PCMV) are considered key factors contributing to patient mortality. This has renewed attention to PCMV, a virus widely prevalent in pigs. Currently, there are no effective drugs or vaccines targeting PCMV, and its high detection difficulty poses challenges for prevention and control research. In this study, antiviral small hairpin RNA (shRNA) was selected and inserted into the Rosa26 and miR-17-92 loci of pigs via a CRISPR/Cas9-mediated knock-in strategy. Further in vitro viral challenge experiments demonstrated that these genetically edited pig cells could effec-tively limit PCMV replication. Through this process, we constructed a PCMV-infected cell model, validated partial viral interference sites, enhanced gene knock-in efficiency, performed gene editing at two different gene loci, and ultimately demonstrated that RNA interference (RNAi) technology combined with CRISPR/Cas9 has the potential to generate pig cells with enhanced antiviral infec-tion capabilities. This opens up possibilities for the future production of pig populations with anti-viral functionalities.

Diarrhea is a common occurrence following vascular organ transplantation, including kidney transplants. It can be induced by non-infectious factors, adverse effects of immunosuppressive drugs, or infectious agents such as viruses, bacteria, fungi, or parasites. Intestinal protozoan parasites, include Cryptosporidium spp., are causes of infectious diarrhea particularly in immunocompromised patients. This review aims to summarize reports on epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment of Cryptosporidium spp. infection in adult patients, particularly following kidney transplantation.

During pregnancy, profound physiological changes occur in the maternal body, including those affecting oral health. Dental stem cells (DSCs) have emerged as promising candidates for regenerative therapies in dentistry. This manuscript delves into the intricate interplay between DSC behavior and maternal oral health during pregnancy. We provide an overview of current knowledge concerning the impact of pregnancy on DSCs, highlighting their potential roles in maintaining oral homeostasis and responding to pathological conditions. Additionally, we identify key research gaps and propose future directions for investigating novel therapeutic strategies leveraging DSCs to improve maternal and fetal oral health outcomes. By elucidating this relationship, we aim to pave the way for innovative approaches in preventive and regenerative dentistry tailored to the unique needs of pregnant women.

(1) Background: Sentinel lymph node (SLN) mapping represents an accurate and feasible technique for the surgical staging of endometrial and cervical cancer. This is commonly performed by conventional laparoscopy or robotic-assisted laparoscopy, but in recent years, a new retroperitoneal transvaginal natural orifice transluminal endoscopic surgery (vNOTES) approach has been described. This technique provides easy visualization of lymphatic afferent vessels and pelvic lymph nodes, early SLNs assessment, and a coherent mapping methodology following the lymphatic flow from caudal to cranial. However, only a few publications have reported it. Following the IDEAL (Idea Development Exploration Assessment Long-term follow-up) framework, research concerning this technique is at stage 2a, with only small case series as evidence of its feasibility. Its standardized description appears necessary to provide the surgical homogeneity required to move further. (2) Methods: description of a standardized approach for retroperitoneal pelvic SLN mapping by vNOTES. (3) Results: we described a 10-step approach to successfully perform retroperitoneal vNOTES SLN mapping, including pre-, intra-, and postoperative management. (4) Conclusions: This IDEAL stage 2a study could help other surgeons approach this new technique, and it proposes a common methodology necessary to evolve through future IDEAL stage 2b (multi-center studies) and stage 3 (randomized controlled trials) studies.

Background/Objectives: The aim of this study was to investigate feasibility and safety of neuromuscular electrical stimulation (NMES) in patients on extracorporeal membrane oxygenation (ECMO) and assess thoroughly any potential adverse events. Methods: We conducted a safety and feasibility study including 16 ICU patients on ECMO support who were admitted to the cardiac surgery ICU from January 2022 to December 2023. Patients underwent a 45-minute NMES session, still on ECMO support, that included a warm up phase of 5 minutes, a main phase of 35 minutes and a recovery phase of 5 minutes. NMES was implemented on vastus lateralis, vastus medialis, gastrocnemius and peroneus longus muscle of both lower extremities. Two stimulators delivered biphasic, symmetric impulses of 75 Hz, with 400 μsec pulse duration, 5 sec on (1,6 sec ramp up and 0,8 sec ramp down) and 21 sec off. The intensity levels aimed to cause visible contractions and be well tolerated. Primary outcomes of the study were feasibility and safety, evaluated by whether the NMES sessions were successfully achieved, and by any adverse events and complications. Secondary outcomes included indices of rhabdomyolysis from biochemical blood test, 24 hours after the application of NMES. Results: All patients successfully completed their 45-minute NMES session, without presenting hemodynamic deterioration, adverse events or signs of rhabdomyolysis. The majority of patients achieved type 4 and 5 quality of muscle contraction. Conclusions: NMES is a safe and feasible exercise methodology in patients supported with ECMO.

Even despite rapid advances in colorectal surgery, morbidity and mortality rates in elective gastrointestinal surgery play a significant role. For decades, there have been tempestuous discussions on preventive measures to minimize the risk of anastomotic dehiscence. When mechanical bowel preparation before elective procedure, one of the key hypotheses, has been introduced into practice, it was assumed that it would decrease number of infectious complications and anastomotic dehiscence. The advancements in antibiotic treatment supported concomitant administration of oral antibiotics and mechanical bowel preparation. In the prospective study conducted at our clinic, we performed left-side colorectal procedures without the prior mechanical preparation. All patients enrolled in the study underwent the surgery and had been observed in the 3rd Surgical Clinic, Faculty of Medicine, Comenius University in Bratislava, Slovakia, from January 2019 to January 2020. As a control group we used similar group of patients with MBP. Our observed group included 87 patients with tumors in the left part of their large intestine (lineal flexure, descendent colon, sigmoid colon, and rectum). Dixon laparoscopic resection was performed in 26 patients. Sigmoid laparoscopic resection was performed in 27 patients. In 12 patients, the procedure was started laparoscopically but had to be converted due to adverse anatomical conditions. The conservative approaches mostly included Dixon resections (19 patients), sigmoid colon resection (5 patients) and left side hemicolectomy (6 patients), and Miles´ tumor resection with rectal amputation (4 patients). Our study highlighted the fact that MBP does not have the unequivocal benefit for patients with colorectal infection, which has an impact on development of anastomotic dehiscence.

Kidney transplant recipients (KTR) show higher morbidity and mortality from COVID-19 than the general population and have an impaired response to vaccination. We analyzed COVID-19 incidence and clinical outcomes in a single-center cohort of approximately 2500 KTR. Between February 1, 2020 and July 1, 2022, 578 KTR were infected with SARS-CoV-2, with 25 (4%) recurrent infections. 208 KTR (36%) were hospitalized, and 39 (7%) died. Among vaccinated patients, infection with the Omicron variant had a mortality of 2%. Unvaccinated patients infected with the Omicron variant showed mortality (9% vs. 11%) and morbidity (hospitalization 52% vs. 54%, ICU-admission 12% vs. 18%) comparable to the pre-Omicron era. Multivariable analysis revealed, being unvaccinated (OR = 2.15, 95% CI [1.38, 3.35]), infection in the pre-Omicron era (OR = 3.06, 95% CI [1.92, 4.87]), and higher patient age (OR = 1.04, 95% CI [1.03, 1.06]) are independent risk factors for COVID-19 hospitalization, whereas steroid-free immunosuppressive regimen was found to reduce the risk of COVID-19 hospitalization (OR = 0.51, 95% CI [0.33, 0.79]). This suggests that both, virological changes in the Omicron variant and vaccination, reduce the risk for morbidity and mortality from COVID-19 in KTR. Our data extend the knowledge from the general population to KTR and provide important insights into outcome during the Omicron era.

Acute and chronic graft versus host disease (a/cGVHD) are major complications of allogeneic stem cell transplantation and a frequent cause of non relapse-mortality. The treatment of a/cGVHD consists of steroid administration at full dose. In the case of aGVHD, around 60 % of patients with grade III/IV fails to respond (steroid-resistant, SR), requiring a second line therapy. Extracorporeal photopheresis (ECP) represents a good option for second line treatment, leading to multiorgan response in several patients. Here, we have evaluated the performances of a cytofluorimetric quality control of the first ECP procedure in 29 patients with severe SR aGVHD who underwent ECP. The quality control represents a check control of in vitro cell apoptosis/death induction in collected and irradiated CD3+ cells by ECP. Our analysis shows that in more than 70 % quality controls a relevant apoptotosis/death of CD3+ cells was observed after cell irradiation, as compared to non-irradiated controls. Albeit observed in a small patients’ series, the occurrence of relevant in vitro effect after ECP relates to less procedures and/or to a better survival on ECP. Age, disease, gender, aGVHD grade and time from transplant to the first ECP had not impact on ECP efficacy in this patients’ series.

Abstract: Obesity and overweight also increasingly affect women of childbearing age and pregnant women. In maternal obesity, the activation of metabolic, inflammatory, and oxidative stress pathways is proven, which appears to be a key step in placental and uterus function pathological changes. Several recent studies have evidenced that aquaporins (AQPs) are critical players in adipose tissue biology and are involved in the onset of obesity. Our studies aimed to investigate the changes in placental volume and vascularization and measure the AQP5 expression and total antioxidant capacity (TAC) in the placenta and uterus tissues in obese and normal-weight mothers. We also aim to measure the AQP5 plasma concentration. We found AQP5 dominance in the uterus and plasma at 34 weeks of normal pregnancy. The placental volume increased, and the vascularization decreased in obese mothers compared to the control. The AQP5 expression increased in the uterus of the obese group and did not change in the placenta. The TAC decreased in the plasma of overweight mothers. We hypothesize that increased AQP5 expression prolongs the length of pregnancy and inhibits the onset of contractions. Based on our findings, we can develop diagnostic tests and provide new targets for tocolytic drug development.

Background/ObjectivesMental health and substance use disorders (MHD, SUD) affect cardiac allograft and VAD recipients and impact their quality of life and compliance. Limited research on MHDs and SUDs in transplant and MCS candidates and recipients. This study compares the incidence of MHDs and SUDs in transplant list, VAD, and post-transplant patients with that in heart failure patients. MethodsStudy cohorts were derived from the TriNetX using ICD-10 codes. Differences in incidence were examined using the log-rank test. Adults with mental health disorders before the window of time were excluded. Propensity score matching was performed using TriNetX to balance demographic and medical comorbidities. Statistical significance was set at p<0.05. All comparisons were made between propensity-matched cohorts. ResultsTransplant waitlist patients showed a statistically significant increase in the incidence of anxiety, panic disorder, adjustment disorder, depression, mood disorder, alcohol use disorder, and eating disorder. Post-transplant patients showed a statistically significant increase in the incidence of depression and opioid use compared to the heart failure population. VAD patients showed a statistically significant increase in the incidence of depression and a statistically significant decrease in panic disorder and anxiety. ConclusionsThe results pave the pathway for further investigations on prevention and coping strategies because deterioration of mental health will significantly impact compliance with medications as well as patient survival and quality of life. The use of opioids for pain management in the early postoperative period should be further investigated to assess its impact on long-term substance use and addiction. .

Pancreas transplantation is a high-risk operation that requires significant skill and expertise from the surgeons and the postoperative care team. Prior to candidate qualification, all contraindications to this procedure must be excluded. The use of screening tools and nutritional assessment aims to emphasize the importance of accurately diagnosing nutritional status in order to implement early nutritional interventions and reduce complications associated with malnutrition. This plays a crucial role in improving postoperative outcomes for patients undergoing pancreas and/or kidney transplantation. Objective: The aim of this study was to analyze the parameters of nutritional status in patients eligible for kidney transplantation and kidney with pancreas transplantation. Methods: The study analyzed the database of hospitalized patients in our Center from 2020 to 2023 to identify preoperative parameters of nutritional status in patients eligible for kidney transplantation (Ktx) and kidney with pancreas transplantation (SPKTx). Participants: A total of 59 patients participated in the study, who were candidates for kidney transplantation (23, including 11 females and 12 males) or kidney with pancreas transplantation (36, including 24 females and 12 males). Parameters examined included: Onoder's Prognostic Nutritional Index (PNIO), Nutrition Risk Index (NRI), ideal body weight (IBW) calculated using the Lorenz formula, and the neutrophil-to-lymphocyte ratio (NLR). All patients admitted to the clinic underwent the NRS-2002 clinical assessment scale for nutritional status. Results: Upon analyzing the obtained results, it was found that BMI was not a good differentiating parameter for the studied groups. The PNIO index also insufficiently differentiated the studied groups, and similarly, the NRI index was a weak differentiating parameter. The NRS-2002 index and albumin level were the best indicators of differences between the groups. In the group of transplantation candidates, several parameters indicated that patients in the Ktx group (kidney transplantation candidates) had better nutritional status than SPKtx candidates (kidney with pancreas transplantation candidates), despite the former group being older patients. Conclusion: It seems that more effort should be made to start a proper nutrition plan for SPKTx (and especially peritoneal dialysis) patients. Regular assessment of nutrition status should be performed. SPKtx patients in the perioperative period should receive parenteral nutrition and, as soon as their general condition allows it, enteral nutrition, taking into account the caloric and protein needs

BACKGROUND: The number of waitlisted patients requiring mechanical circulatory support (MCS) as a bridge to heart transplantation is increasing. The data concerning the results of double-bridge strategy are limited. We sought to investigate the post-transplant outcomes across the different bridge strategies. METHODS: We retrospectively reviewed a heart transplantation database from Jan 2009 to Jan 2019. Intra-aortic balloon pump (IABP), extracorporeal membrane oxygenation (ECMO), and ventricular assist devices (VAD) were the MCS that we investigated. The pre- and post-transplant characteristics and variables of patients bridged with the different types of MCS were collected. The post-transplant survival was compared using Kaplan-Meier survival analysis. RESULTS: A total of 251 heart transplants were reviewed; 115 without MCS and 136 with MCS. The patients were divided to five groups: Group 1 (no MCS): n=115; Group 2 (IABP): n=15; Group 3 (ECMO): n=33; Group 4 (ECMO-VAD): double-bridge (n=59); Group 5 (VAD): n=29. Survival analysis demonstrated that the 3-year post-transplant survival rates were significantly different among the groups (Log-rank p < 0.001). There was no difference in survival between group 4(ECMO-VAD) and group 1(no MCS)1 (p = 0.136), or between group 4(ECMO-VAD) and group 5(VAD) (p = 0.994). Group 3(ECMO) had significantly inferior 3-year survival than group 4(ECMO-VAD) and group 5(VAD). CONCLUSION: Double bridge may not lead to worse mid-term results in patients who could receive a transplantation. Initial stabilization with ECMO for critical patients before implantation of VAD might be considered as a strategy for obtaining an optimal post-transplant outcome.

Pueraria mirifica (PM), a plant whose dried and powdered tuberous roots are now widely used in rejuvenating preparations to promote youthfulness in both men and women, may have major estrogenic influence. In this study, we investigated modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized animals at doses of 0.03%, 0.3%, and 3% in a phytoestrogen-low diet for 2 weeks caused significant increase in uterus weight. Secondly, a 4 week PM application to non-operated rats at a dose of 3% after 7,12-dimethylbenz[a]anthracene (DMBA) initiation resulted in significant elevation of cell proliferation in the mammary glands. In a third experiment, postpubertal administration of 0.3% (200 mg/kg body weight (b.w.)/day) PM to 5-week-old non-operated animals for 36 weeks following initiation of mammary and endometrial carcinogenesis with DMBA and N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG), respectively, resulted in significant increase of mammary adenocarcinoma incidence. A significant increase of endometrial atypical hyperplasia multiplicity was also observed. Furthermore, PM at doses of 0.3% and, more pronouncedly, of 1% induced dilatation, hemorrhage and inflammation of the uterine wall. In conclusion, postpubertal long-term PM administration to Donryu rats exerts estrogenic effects in the mammary gland and uterus, and at a dose of 200 mg/kg b.w./day was found to promote mammary carcinogenesis initiated by DMBA.

A positive fluid balance may evolve to fluid overload and associate with organ dysfunctions, weaning difficulties, and increased mortality in ICU patients. We explored whether individualized fluid management, assessing fluid-responsiveness via passive leg-raising maneuver (PLR) before spontaneous breathing trial (SBT) associated with less extubation failure in ventilated patients with high fluid balance, admitted to the ICU after liver transplantation (LT). We recruited 15 LT patients in 2023. Postoperative fluid balance was +4476 [3697,5722] mL. PLRs were conducted at ICU admission (T1) and pre-SBT (T2). Cardiac index (CI) changes were recorded before and after SBT (T3). Seven patients were fluid responsive at T1, and 12 at T2. No significant differences occurred in hemodynamic, respiratory, and perfusion parameters between fluid-responsive and fluid-unresponsive patients at any time. Fluid-responsive patients at T1 and T2 increased their CI during SBT from 3.1 [2.8,3.7] to 3.7 [3.4,4.1] mL/min/m2 (p= 0.045). All fluid-responsive patients at T2 were extubated after SBT and consolidated extubation. Two out of three of fluid-unresponsive patients experienced weaning difficulties. We concluded that fluid-responsive patients post-LT may start weaning earlier and achieve successful extubation despite high postoperative fluid balance. This highlights the profound impact of personalized assessment of cardiovascular state on critical surgical patients.

Background & aims: Malnutrition in lung transplant (LT) candidates increases postoperative morbidity and mortality. Early diagnosis of malnutrition could attenuate adverse prognostic factors. This study aimed to assess the prevalence of nutritional risk and malnutrition using GLIM criteria in LT candidates and clinically characterize those with malnutrition. Methods: A prospective longitudinal study was conducted from 2000 to 2020 of LT candidates who underwent complete nutritional assessment (nutritional screening, anthropometry, bioelectrical impedance, blood laboratory tests and malnutrition diagnosis using GLIM criteria). Results: Obstructive diseases (45.6%), interstitial diseases (36.6%) and cystic fibrosis/non-cystic fibrosis bronchiectasis (15.4%) were the main conditions assessed for LT. Of the 1060 candidates evaluated, 10.6% were underweight according to BMI, 29% were at risk of malnutrition and 47% were diagnosed with malnutrition using GLIM criteria. Reduced muscle mass was the most frequent GLIM phenotypic criterion. Malnutrition was more prevalent in patients with cystic fibrosis/non-cystic fibrosis bronchiectasis (84.5%), obstructive (45.4%) and interstitial (31.3%) diseases. GLIM criteria detected some degree of malnutrition in all diseases requiring LT and identified patients with higher CRP levels and worse respiratory function, anthropometric measurements and visceral protein and lipid profiles. Conclusions: LT candidates present a high prevalence of malnutrition using the GLIM algorithm. GLIM criteria detected malnutrition in all diseases requiring LT and defined patients with worse clinical-analytical profiles.

Prevention of infections is crucial in solid organ transplant (SOT) candidates and recipients. These pa-tients are exposed to an increased infectious risk due to previous organ insufficiency and to pharmaco-logic immunosuppression. Besides infectious-related morbidity and mortality, this vulnerable group of patients is also exposed to the risk of acute decompensation and organ rejection or failure in the pre- and post-transplant period respectively, since antimicrobial treatments are less effective than in the immunocompetent patients. Vaccination represents a major preventive measure against specific infec-tious risks in this population but as responses to vaccines are reduced, especially in the early post-transplant period or after treatment for rejection, an optimal vaccination status should be obtained prior to transplantation whenever possible. This review reports the currently available data on the indications and modalities of vaccination in SOT adult candidates and recipients.

Transplanted organs experience several episodes of ischemia and Ischemia-reperfusion. The graft injury resulting from ischemia-reperfusion (IRI) remains a significant obstacle to the successful survival of transplanted grafts. Temperature plays an important role in cellular metabolic rates since biochemical reactions are highly temperature dependent. Therefore, ischemia-triggered degradative reactions could be mitigated by lowering temperature. Whether a local hypothermia on liver before blockage of blood flow protects liver grafts against IRI has not been investigated. In this study, we applied local hypothermia to mouse donor livers for a specific duration before stopping blood flow to liver lobes, a procedure called "liver precooling." Mouse donor liver temperature in control groups was controlled at 37ºC. Subsequently, the liver donors were preserved in cold University of Wisconsin solution for various durations followed by orthotopic liver transplantation. Liver graft injury, function and inflammation were assessed at 1- and 2-days post-transplantation. Liver precooling exhibited a significant improvement in graft function, revealing more than a 47% decrease in plasma aspartate transaminase (AST) and alanine aminotransferase (ALT) levels, coupled with a remarkable reduction of approximately 50% in liver graft histological damage compared to the control group. The protective effects of liver precooling were associated with the preservation of mitochondrial function, substantial reduction in hepatocyte cell death, and a significantly attenuated inflammatory response. A retrospective analysis of patient data revealed a close correlation between hypothermia and enhanced liver graft function. Taken together, reduction of the cellular metabolism and enzymatic activity to a minimum level before ischemia protects against IRI during transplantation.

This review provides insight into the role that obesity, but especially mediators of the adipose tissue, have in both renal disease and transplantation. In particular, we focus on the functions of leptin and adiponectin, inflammatory mediators with widely known clinical implications, as well as on the role of arachidonic acid-derived eicosanoid metabolites. These latter compounds, epoxyeicosatrienoic (EETs) and hydroxyeicosatetraenoic (HETEs) acids, which modulate the liberation of cytokines in the adipose tissue, are generated in the epoxygenase pathway of arachidonic biotransformation via CYP450 enzymes. There is accumulating evidence suggesting that EETs and HETEs may have a critical role in the onset and outcome of chronic kidney disease and renal transplantation. Finally, we also discuss the reported effect that the presence of genetic variants in leptin, adiponectin, EETs and HETEs-related genes may cause in renal patients and recipients. The levels of cytokines of the adipose tissue and related compounds play a remarkable role in both renal disease and transplant. Accordingly, novel therapeutic strategies are being developed based on the modulation of their concentrations in patients with various diseases.

We present the full case pictorial assay including preoperative imaging as well as the surgical correction of the uterine anomaly and associated complication of a very rare case of occult unicornuate right uterus with rudimentary non-communicating functioning left horn and its natural evolution following an initially incomplete surgical treatment.

This study describes the characteristics of women who contacted an active program performing uterus transplantation (UTx) in the US expressing interest in becoming a uterus transplant recipient or a living donor. Basic demographic and self-reported clinical information was collected from women who contacted any of the three US UTx programs from 2015 to July 2022. The three centers received 5194 inquiries about becoming a UTx recipient during the study timeframe. Among those reporting a cause of infertility, almost all (4066/4331, 94%) were absence of a uterus, either congenitally (794/4066, 20%) or secondary to hysterectomy (3272/4066, 80%). The mean age was 34 years, and 49% (2545/5194) had at least one child at the time of application. The two centers using living donors received 2217 inquiries about becoming living donors. The mean age was 34 years, and 60% (1330/2217) had given birth to ≥1 child. While most of the UTx clinical trial evidence has focused on young women with congenital absence of the uterus, these results show interest from a much broader patient population in terms of age, cause of infertility, and parity. These results raise questions about whether and to what extent the indications and eligibility criteria for UTx should be expanded as the procedure transitions from the experimental phase to being offered as a clinical treatment.

Understanding vaccine hesitancy in organ transplant recipients (OTR) is critical, given clear, alt-hough attenuated, benefits from vaccination. Adult OTR were surveyed regarding vaccine-related values and a novel outcome variable called Vaccine Acceptance Composite Score (VACS) was built as the average Likert score of 7 domains of vaccination confidence. Of 46 OTR included (93.5% kidney transplant recipients), 32.6% were female, 13.3% Black, 6.77% Hispan-ic/Latino/a/x; median age was 58 years. Patients were most concerned about COVID-19 vac-cine-associated risks (46.3%), its potential effect on allograft (47.6%) and motives of government officials involved with vaccine policy (55.6%). Politically conservative patients were likely to have a significantly lower VACS, while those who lived with someone ≥65 had a higher VACS. The VACS was not significantly associated with race, income, religious beliefs, comorbidities, COVID-19 history, or influenza vaccination status. Higher VACS was significantly associated with ≥3 and ≥4 COVID-19 immunizations. This study highlighted political beliefs and elderly household members as correlates of vaccine acceptance among OTR. The VACS may be a useful tool to help standardize multifaceted analyses in vaccination-focused behavioral research, as well as identify individuals and groups at risk for vaccine hesitancy, who may benefit from tai-lored outreach and educational interventions.

In kidney transplant recipients, belatacept is usually pursued indefinitely after it has been started. In the setting of the belatacept shortage and after having evaluated the benefit-risk ratio, we established a strategy consisting of time-limited belatacept therapy / transient calcineurin inhibitor withdrawal, whose results are analyzed in that study. We considered all the kidney transplant recipients that had been switched from conventional immunosuppressive therapy to belatacept and then for whom belatacept has been withdrawn intentionally. Furthermore, in the first 8 patients, we assessed changes in peripheral blood mononuclear cells (PBMC) transcriptome using RNAseq before and 3 months after belatacept withdrawal. Over the study period, 28 out of 94 patients had belatacept intentionally withdrawn including 25 (89%) switched to low-dose CNI. One rejection due to poor compliance occurred. The eGFR after 12 months remained stable from 48 ± 19 ml.1.73m^-2 to 46 ±17 ml.1.73m^-2 (p = 0.68). However, patients that resumed belatacept / withdrew CNIs (n=10) had a trend towards a better eGFR comparing with the others (n =15): 54 ± 20 ml.1.73m^-2 vs eGFR 43 ± 16 ml.1.73m^-2 respectively (p = 0.15). The only factor associated with belatacept resumption was when the withdrawal took place during the COVID-19 outbreak. Transcriptome analysis of PBMCs, did not support rebound in alloimmune response. These findings underpin the use of belatacept as part of a time-limited therapy, in selected kidney transplant recipients, possibly as an approach to allow efficient vaccination against SARS-Cov-2.

Globally, the adoption of Solid Organ Transplantation (SOT) as first-line therapy for end-stage organ failure has not come without its share of complications. Enterococcal endocarditis poses a substantial risk to renal transplant patients, and multiple factors must be considered due to the grave nature of this infection. Such factors include addressing multidrug-resistant organisms, antibiotic therapy-related toxicity, and preserving the transplanted organ. Additional considerations include salvaging an affected cardiac valve and avoiding the need for a valve replacement with the attendant complications. Ampicillin and gentamicin have historically been the standard of care as first-line treatment for many years until the aminoglycoside sparing regimen of ampicillin and ceftriaxone showed non-inferiority in clinical studies. We present a second case report with an aminoglycoside sparing regimen of ampicillin and daptomycin in a renal transplant patient who developed Enterococcus faecalis endocarditis. We conclude with a brief review of published research with this combination.

Heart transplantation (HT) represents the mainstream therapy of end-stage heart failure for selected patients with a median survival of more than 10 years after surgery and substantial improvement in quality of life. Current guidelines suggest a variety of examinations including invasive (coronary angiography and endomyocardial biopsy (EBM) and non-invasive methods (echocardiography, stress echocardiography, computed tomography, PET and MRI) to monitor HT patients. Guidelines do not specify the timing of echocardiographic evaluations and do not recommend echocardiography as an alternative to serial EMB in rejection monitoring [2]. They still recommend as gold standard coronary angiography to be done 1 year after surgery and every 2 years after. In this review we will discuss the advantages of non-invasive techniques over the invasive ones for an adequate follow-up of HT patients.

Hepatocellular carcinoma is the most common primary malignant hepatic tumor and occurs most often in the setting of chronic liver disease. Liver transplantation is a curative treatment option and is an ideal solution because it solves the chronic underlying liver disorder while removing the malignant lesion. Because of organ shortages this treatment can only be applied to carefully selected patients according to clinical guidelines to minimize risk of recurrence. Artificial intelligence is an emerging technology with multiple applications in medicine with a predilection for domains that work with medical imaging like radiology. With the help of these technologies laborious tasks like segmentation can be automated and workflow in radiology departments can be improved. Other roles include in depth pixel-wise analysis of lesions by radiomics or deep learning in order to find new imaging criteria that allow better prediction of treatment response or risk of recurrence. Liver transplant is an ideal treatment for patients with hepatocellular carcinoma in the setting of chronic liver disease and artificial intelligence could provide solutions for improving the management of liver transplant candidates to improve survival.

Abstract Kidney transplant recipients, because of a weak immune response due to the assumption of immunosuppressant are exposed to the risk of COVID-19 infection. This fact realize the problem on how to treat the severe infection without carrying the risk of acute rejection due to the reduction of the immunosuppressive drugs. The best are the prophylactic measures to be taken before transplantation as vaccination. If the patient is already transplanted, three measures may be undertaken: Vaccination, use of monoclonal antibodies, use of therapeutic antiviral small molecules. Concerning vaccination is still debated which one is the best and how many doses should be given. The surge of new virus variant is the major problem and invites to find new active vaccines. In addition, not all the transplanted patients develop antibodies. The other measure is the use of monoclonal antibodies. They may be used as prophylaxis or in the early stage of the disease. Finally, the antiviral small molecules may be used again as prophylaxis or treatment. Their major drawback are the interference with the immunosuppressive drugs and the fact that some of them cannot be administered to patients with low eGFR.

Novel coronavirus infection is a recent infective agent that causes severe potentially fatal pneumonia. The clinical presentation includes asymptomatic infection, severe pneumonia, and acute respiratory failure. Data pertaining to the clinical presentation of solid organ transplant recipients are scarce. Two cases of novel coronavirus infection in two recipients of renal transplant with variable clinical presentations and outcomes are reported. The first patient presented with progressive respiratory symptoms, acute renal failure, and passed away, whereas the second one, although presented with respiratory tract symptoms and hypoxemia remained stable and exhibited an excellent clinical recovery despite recent reception of thymoglobulin induction. This paper reports rare cases of novel coronavirus infection in renal transplant recipients. For an enhanced insight of the novel coronavirus infection and acute kidney injury on the clinical presentation, severity, and outcome in solid organ transplant recipients, further investigations are required.

Liver transplantation is currently the only curative therapy for patients with liver cirrhosis. Not all patients in the natural course of the disease will undergo transplantation, but the majority of them will experience portal hypertension and its complications. In addition to medical and endoscopic therapy, a key role in managing these complications is played by the placement of a transjugular intrahepatic portosystemic shunt (TIPS). Some indications for TIPS placement are well-established and they are expanding and broadening over time. This review aims to describe the role of TIPS in managing patients with liver cirrhosis, considering them as potential candidates for liver transplantation. As far as is known TIPS placement seems not to affect the surgical aspects of liver transplantation, in terms of intra operative bleeding rates, postoperative complications or length of stay in the Intensive Care Unit. However, the placement of a TIPS “towards transplant" can offer advantages in terms of enhancing the patient's clinical condition at the time of transplantation and improving patient survival. Additionally, the TIPS procedure can help preserve the technical feasibility of the transplant itself. In this context, indications for TIPS placement may be expanded and considered at an earlier stage. TIPS insertion can also lead to serious adverse events and there are no evidence-based recommendations on this topic to date. For these reasons further studies are needed to make reliable recommendations for TIPS in the pre-transplant setting.

Background: Chronic kidney disease (CKD) is a common complication of non-kidney solid organ transplant (NKSOT). Identifying predisposing factors is crucial for an early approach and correct referral to nephrology. Methods: This is a single-center retrospective observational study of a cohort of CKD patients under follow-up in Nephrology Department between 2010 to 2020. Statistical analysis was performed between all the risk factors and four dependent variables: end-stage renal disease (ESKD), increased serum creatinine ≥50%, renal replacement therapy (RRT), and death in pre-transplant, peri-transplant and post-transplant period. Results: 74 patients were studied (7 heart transplant, 34 liver transplants, and 33 lung transplant). Patients who were not followed-up by nephrology in the pre-transplant (p&lt;0.027), peri-transplant (p&lt;0.046), and the longest time until outpatient clinic follow-up (HR 1,032) were associated with a higher risk of creatinine increase ≥50%. Receiving a lung transplant conferred higher risk than liver or hear transplant for developing a creatinine increase ≥50% and ESKD. Peri-transplant mechanical ventilation, peri-transplant and post-transplant anticalcineurin overdose, nephrotoxic and the number of hospital admissions were significantly associated to present a creatinine increase ≥50% and develop ESKD. Conclusion: An early follow-up by the nephrology department was associated with a decrease in the worsening of renal function.

Kidney transplantation is the treatment of choice for patients with end-stage disease. To expand the donor reserve, it is necessary to use marginal/sub optimal donors that provide marginal organs. We retrospectively evaluated the short and long-term outcome of elderly kidney transplantation using allografts with vascular abnormalities. Between January 1999 and December 2018, 740 transplants from cadaveric donors were performed. Thirty-four elderly patients received a kidney transplantation with vascular anatomical variants (Group 1) were compared with 34 patients who received a kidney transplantation with single renal artery (SRA) (Grroup2) pair-matched by age, dialysis age, donor age, comorbidity. All participants completed the Long Form International Physical Activity Questionnaire (IPAQ) at baseline and after 4, 8, and 12 weeks after transplantation. The overall rate of surgical complications was 17.6% in Group 1 and 20.6% in Group 2, indicating that kidney with vascular anatomical variant might be successfully transplanted. Our data also emphasizes the importance of individualized physical activity in kidney transplantation with multiple arteries. Physical activity should be considered as an essential part of the medical care for renal-transplanted recipients.

Alternaria alternata is a saprophyte and is also known to cause many opportunistic infections in humans. Alternaria infections are important factors of morbidity and mortality in im-mune-compromised and solid organ transplant (SOT). Sensitivity to the airborne fungus Alter-naria alternata is also believed to be a common cause of allergic asthma. Therapies are limited by the lack of knowledge about the role of individual fungal gene products and symptoms in im-mune-compromised and transplant patients. This review summarizes the published case studies on Alternaria alternata infections in transplant patients.

Background Recent studies indicate that donor innate immune responses participate in initiating and accelerating innate responses and allorecognition in the recipient. These immune responses negatively affect recipient outcomes and predispose recipients to allograft coronary artery vasculopathy (CAV). We hypothesized that donor cause of death (COD) associated with higher levels of innate immune response would predispose recipients to more adverse outcomes post-transplant, including CAV. Methods We performed a single-institution retrospective analysis comparing donor characteristics and COD to recipient adverse cardiovascular outcomes. We analyzed the medical records of local adult donors (age 18-64) in a database of donors where adequate data was available. We linked donor characteristics and COD to recipient adverse cardiac outcomes after transplant, including cardiovascular (CV) death and incidence of significant antibody-mediated rejection (pAMR) after transplant (>2 episodes of pAMR within 90 days post-transplant). The data were analyzed using logistic regression, log-rank test of differences, and Tukey Contrast. Results Donor advanced age, female sex, and CODs of motor vehicle accident and intracranial hemorrhage were significantly associated with a higher incidence of recipient CV death and early pAMR compared to other donor characteristics and CODs. Conclusions In this single institution study, we found that recipients with hearts from donors over 40 years, donors who were female, or donors who died with a COD of motor vehicle accidents or intracranial hemorrhage had a higher frequency of CV related deaths and early pAMR. Donor monitoring and potential treatment of innate immune activation may decrease subsequent recipient innate responses and allorecognition stimulated by donor derived inflammatory signaling which lead to adverse outcomes.

Retinal pigment epithelium (RPE) replacement therapy is evolving as a feasible approach to treat age-related macular degeneration (AMD). In majority of the preclinical studies, RPE cells are transplanted as cell suspension into immunosuppressed animal eyes and transplant effects were monitored only short-term. We investigated long-term effects of human iPSC derived RPE transplants in immunodeficient Royal College of Surgeons (RCS) rat model, in which RPE dysfunction lead to photoreceptor degeneration. iPSC-RPE cultured as polarized monolayer on nanoengineered ultrathin parylene C scaffold was transplanted into the subretinal space of 28-day old immunodeficient RCS rat pups and evaluated after 1, 4 and 11 months. Assessment at early time points showed good iPSC-RPE survival. The transplants remained as a monolayer, expressed RPE specific markers, performed phagocytic function and contributed to vision preservation. At 11-month post-implantation, RPE survival was observed only in 50% of the eyes that were concomitant with vision preservation. Loss of RPE monolayer characteristics at the 11month time point was associated with peri-membrane fibrosis, immune reaction through activation of macrophages (CD 68 expression) and transition of cell fate (expression of mesenchymal markers). The overall study outcome supports the therapeutic potential of RPE grafts despite the loss of some transplant benefits during long-term observations.

Urinary tract infections in kidney transplant patients are a real challenge. We conducted a retrospective observational study, enrolling all kidney transplant patients hospitalized for urinary tract infection (UTI), with the objective to evaluate the epidemiology, clinical sta-tus, therapeutic management, and clinical outcome of kidney transplant patients hospi-talized for urinary tract infection in a university hospital. From our real-life experience, infection with multidrug-resistant germs was confirmed as a risk factor for the severe evolution of the infection and at the same time the re-evaluation of immunosuppressive therapy could be an important therapeutic strategy in the course of infection. Prompt ini-tiation of empiric antibiotic therapy upon initiation of microbiological investigations could potentially reduce the risk of severe infection progression.

Background & aims. The fourth dose of anti-SARS-CoV-2 vaccine slightly improved the humoral response among previously seronegative liver transplant (LT) recipients. Mycophenolate (MMF) treatment worsens the vaccination response. This study aimed to evaluate whether temporary MMF interruption might improve immunogenicity of the fourth anti-SARS-CoV-2 BNT16b2 vaccine dose in nonresponsive LT recipients. Methods. LT recipients negative for anti-spike glycoprotein-specific immunoglobulin G receptor-binding domain (s-RBD) antibodies after the third vaccine dose were enrolled. Anti-SARS-CoV-2 spike-specific T cell responses were measured before and two months following the fourth vaccine dose, and anti-SARS-CoV-2-s-RBD antibodies also 6 months thereafter. MMF was suspended two weeks before and after vaccination. Results. Five LT recipients were enrolled. After a mean of 78 days after vaccination, all patients tested positive for anti-SARS-CoV-2-s-RBD antibodies. The mean antibody titer was 8944 UI/ml. The positive antibody response was maintained during a mean of 193 days of follow-up. Three patients developed a positive T cell response. Two patients (one positive for T cell response) developed a self-limited SARS-CoV-2 infection. Conclusions. Suspending MMF prior to the fourth dose of anti-SARS-CoV-2 mRNA vaccine seems feasible and safe. This procedure could restore vaccine-induced immunogenicity in a large portion of previously nonresponsive LT recipients.

Tuberculosis (TB) remains a global public health issue, particularly in developing countries. Hematopoietic stem cell transplant (HSCT) recipients are at elevated risk for TB due to immunosuppression. This retrospective study (2005-2022) assessed a preemptive latent tuberculosis infection (LTBI) screening and treatment strategy in 338 HSCT recipients and their donors. Screening included tuberculin skin test (TST) or QuantiFERON-TB Gold (QFT), and pulmonary imaging, with positive cases receiving isoniazid (INH) therapy. Statistical analyses aimed to compare TB reactivation rates, overall survival (OS), and relapse-free survival (RFS) across HSCT groups. Of 338 patients, 92 (27%) were diagnosed with LTBI. Screening involved TST in 325 cases and QFT in 13. INH therapy was completed by 81 patients, with 5 discontinuing due to hepatotoxicity. The cumulative incidence of active TB was 0.6%, and LTBI reactivation rate in patients who received INH was 1.2%. LTBI status did not affect OS or RFS. Our study exemplifies the effectiveness of LTBI protocols incorporating TST/QFT and CT-scan testing, followed by INH therapy, in reducing TB reactivation among HSCT recipients in a high-burden region.

Abstract Sodium glucose cotransporter type 2 inhibitors are a new class of drugs acting on cardiovascular system, renal and metabolism in a multiple way. Indeed, even their principal action is on the transporter of sodium and glucose in the convoluted distal tubule, they have multiple actions as antifibrotic and endothelial protective action. Their principal mechanism consist in the loss of sodium and glucose. Therefore, they have effect on blood pressure and glucose metabolism. In a first period their use has been in the diabetic general population, later on some studies documented their activity in non-diabetic general population, in heart failure in chronic kidney disease. Only in recent years several small studies documented their efficacy in diabetic and non-diabetic kidney transplant patients, larger studies are few and very recent and open new ways for these drugs

Immunosuppressed kidney transplant (KT) recipients respond weaker to COVID-19 vaccination than immunocompetent individuals. We tested antiviral IgG response in 99 KT-recipients and 66 healthy volunteers who were vaccinated with mRNA-1273 Moderna or BNT162b2 Pfizer-BioNTech vaccines. A subgroup of participants had their peripheral blood leukocytes (PBLs) evaluated for the frequency of T helper 1 (Th1) cells producing IL-2, IFN-γ and/or TNF-α, and IL-10-producing T-regulatory 1 (Tr) cells. Among KT-recipients, 45.8% had anti-SARS-CoV-2 IgG compared to 74.1% of healthy volunteers (p=0.009); also, anti-viral IgG levels were lower in recipients than in volunteers (p=0.001). When defined as non-responders (≤2,000 U/ml IgG), Moderna’s group had 10.8% and Pfizer-BioNTech’s group had 34.3% of non-responders at 6 months (p=0.023); similarly, 15.7% and 31.3% non-responders were in Moderna and Pfizer-BioNTech groups at 12 months, respectively (p=0.067). There were no non-responders among controls. Healthy volunteers had higher Th1 levels than KT recipients, while Moderna produced higher Th1 response than Pfizer-BioNTech. In contrast, Pfizer-BioNTech vaccine induced higher Tr1 response than Moderna vaccine (p&lt;0.05); overall, IgG levels correlated with Th1(fTTNF-α)/Tr1(fTIL-10) ratios. We propose that the higher number of non-responders in Pfizer-BioNTech group than Moderna group was caused by more potent activity of regulatory Tr1 cells in KT-recipients vaccinated with Pfizer-BioNTech vaccine.

Subclinical inflammation in protocol biopsies relates to tacrolimus exposure and human leukocyte antigen (HLA) matching. We aimed to characterize transcripts associated with rejection and tacrolimus exposure and its association with transplant outcome. We tested whether gene expression is associated with rejection using strictly normal protocol biopsies (n = 17) and biopsies with TCMR or ABMR according to Banff criteria (n = 12). Subsequently, we analyzed these transcripts in a set of 4-month protocol biopsies (n = 137) to assess their association with donor and recipient characteristics, the intensity of immunosuppression, and graft outcome. Differential expression (FDR&gt;3) between normal and rejection biopsies yielded a set of 111 genes. Nineteen out of these 111 genes were correlated with tacrolimus trough levels (TAC-C0) at the time of biopsy in the protocol biopsy cohort (n=137) and allowed us to define 2 clusters of biopsies. The 2 clusters differed in donor age and tacrolimus levels. Subclinical rejection, including borderline lesions, tended to occur in the same cluster. Logistic regression analysis indicated that TAC-C0 at the time of biopsy (OR: 0.83, 95%CI:0.72-0.06, p=0.0117) was associated with cluster 2. In a follow-up averaging 70±30 months, this patient group displayed a significant decline in renal function (p=0.0135). The expression of rejection-associated transcripts in early protocol biopsies is associated with tacrolimus exposure and a faster decline in renal function.

Purpose: Kidney Transplant Recipients (KTRs) tend to develop infections with characteristic epidemiology, presentation and outcome. While infective endocarditis (IE) is among such complications in KTRs, literature is scarce. We describe the presentation, epidemiology, and factors associated with IE in KTRs. Methods: We performed a retrospective case/control study which included patients from two centers. First episodes of definite or possible IE (Duke criteria), in adult KTRs from January 2007 to December 2018 were included, as well as two controls per case, and followed until December 31 2019. Clinical, biological, and microbiological data and the outcome were collected. Survival was studied using the Kaplan-Meier method. Finally, we searched for factors associated with the onset of IE in KTRs by the comparison of cases and controls. Results: Seventeen cases and 34 controls were included. IE was diagnosed after a mean delay of 78 months after KT, mostly on native valves of the left heart only. Pathogens of digestive origin were most frequently involved (six Enterococcus spp, three Streptococcus gallolyticus and one Escherichia coli), followed by Staphylococci (three cases of S. aureus and S. epidermidis each). Among the risk factors evaluated only age was significantly associated with the occurrence of IE in our study (63.8 years for cases vs. 55.6 years for controls, P=0.03) Patient and death-censored graft survival were greatly diminished five years after IE compared to controls being 50.3% vs. 80.6% (p<0.003) and 29.7% vs. 87.5% (p<0.002), respectively. Conclusion: IE in KTRs is a disease that carries significant risks both for the survival of the patient and the transplant.

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a high rate of mortality in kidney transplant recipients (KTRs). The current vaccine strategy for KTRs seems to be unable to provide effective protection against coronavirus disease 2019 (COVID-19) [2] and the occurrence of severe COVID-19 in some vaccinated KTRs suggested a lack of immunity. We analized here the antibody response in a group of 32 kidney transplant recipients (KTR) followed at the Nephrology and Dialysis unit of the Hospital Pio XI of Desio, Italy, compared with a group of 23 healthy workers classified as Late responders (HCW-LR) (10 males age 27-62) and 13 females (age 46-64). We observed that the patients need additional vaccine boosters due to their immunocompromised status and therapy to protect them from infections related to viral variants, in accordance with the literature.

Tixagevimab/cilgavimab (TIXA/CILGA) was introduced in early 2022 as a promising new drug for pre-exposure prophylaxis against COVID-19 in immunocompromised patients. The aim of our study was to evaluate the efficacy and safety of TIXA/CILGA in a Slovenian national cohort of kidney transplant recipients as pre-exposure prophylaxis in the Omicron era. Demographic, clinical, laboratory, and therapeutic data were collected from electronic and paper medical rec-ords. Of the 106 patients who received TIXA/CILGA, 6 patients (5.7%) subsequently acquired SARS-CoV-2 breakthrough infection. The incidence of SARS-CoV-2 infection was only slightly lower compared with patients who did not receive TIXA/CILGA (7.0%). All patients who re-ceived TIXA/CILGA had a mild disease course, whereas 20% of patients who did not receive TIXA/CILGA required hospitalization and two patients died. Adverse effects most likely related to TIXA/CILGA occurred in 12% of patients, one of whom experienced deep vein thrombosis. None of the patients suffered acute myocardial infarction or cerebrovascular insult. Overall, the benefit of added protection for kidney transplant patients appears to outweigh the potential risk of adverse events and provide additional protection against severe COVID-19 protection.

Many centers worldwide raised the concern that immunocompromised patients for solid organ transplantation may be at high risk of developing a severe respiratory disease by COVID-19. Currently, there are no specific data on the COVID-19 in patients with generalized immunosuppression and transplantation.In this narrative review, we reported the main data of COVID-19 in patients with solid organ transplantation presented in the literature. The aim is to elaborate a strategy for tailored management, from diagnosis to therapy.The management of adult patients with solid organ transplantation and COVID-19 is a challenge for the clinicians. There is a lack of data in the literature, but three key-points are crucial: in the “pandemic era,” consider the symptomatic patient as positive for COVID-19 until proven otherwise; adjust/stop immunosuppressive agents; protect graft function with adequate route and dose administration of glucocorticoid and supportive measures. For pediatric patients, data are scarce. It is unclear if immunosuppression in patients with solid organ transplantation alters the predisposition to acquiring COVID-19 or if the disease implications are modified for better or for worse. Further studies are needed.

Lung transplantation offers patients with end stage lung disease an opportunity for a better quality of life, but with limited organ availability it is paramount that selected patients have the best opportunity for successful outcomes. Nutrition plays a central role in post-surgical outcomes and historically, body mass index (BMI) has been used as the de facto method of assessing a lung transplant candidate’s nutritional status. Here we review the historical origins of BMI in lung transplantation, summarize the current BMI literature, and review studies of alternative/complementary body composition assessment tools, including lean psoas area, creatinine-height index, leptin, and dual x-ray absorptometry. These body composition measures quantify lean body mass versus fat mass and may provide a more comprehensive analysis of a patient’s nutritional state than BMI alone.

Bloodstream infection (BSI) after pediatric liver transplantation (PLT) is a common and severe complication that affects patient survival. Children with biliary atresia (BA) are at an increased risk for clinically significant infections. This study evaluated the impact of post-PLT BSI on clinical outcomes in children with BA. A total of 67 patients with BA aged &lt;18 years who underwent PLT between April 2006 and September 2020 were analyzed and divided into two groups according to the occurrence of post-PLT BSI within 1 month (BSI vs. no BSI = 13 [19.4%] vs. 54 [80.6%]). The BSI group was significantly younger at the time of PLT and had a higher frequency of BSI at the time of PLT than the no BSI group. Early vascular complications within 3 months and reoperations were significantly more frequent in the BSI group. Univariate and multivariate analyses revealed that bacteremia within 1 month of PLT and graft-to-recipient weight ratio &gt;4% were significantly associated with vascular complications. In conclusion, BSI after PLT is associated with increased vascular complications and reoperations. Proper control of bacterial infections and early liver transplantation before uncontrolled BSI may reduce vascular complications and unexpected reoperations in children with BA.

Acute and chronic transplant rejections due to alloreactivity are essential contributors to graft loss. However, the strength of alloreactivity is biased by non-immunological factors such as ischemia reperfusion injury (IRI). Accordingly, protection from IRI could be favorable in terms of limiting graft rejection. Caveolin-1 (Cav-1) is part of the cell membrane and an important regulator of intracellular signaling. Cav-1 has been demonstrated to limit IRI and to promote survival of a variety of cell types including renal cells under stress conditions. Accordingly, Cav-1 could also play a role in limiting anti-graft immune responses. Here, we evaluated a possible association between pretransplant serum concentrations of Cav-1 and the occurrence of rejection during follow up in a pilot study. Therefore, Cav-1-serum concentrations were analyzed in 91 patients at the time of kidney transplantation and compared to the incidence of acute and chronic rejection. Higher Cav-1 levels were associated with lower occurrence of acute rejection episodes. Moreover, Cav-1 could be therapeutically useful for attenuating graft rejection.

This strategy had a very fast and good impact on the patient’s health; the CCM improved heart failure symptoms, hemodynamics flow and cardiac functionality. Moreover, after a relatively short time, the patient comes from persistent AF to Sinus Rhythm, although he starts with a severe bi-atrial dilatation. These parameters were stable during an extended follow-up of 18 months.

Autoimmune limbic encephalitis (LE) is a rare, but devastating complication of allogeneic hem-atopoietic stem cell transplantation (HSCT). There is currently limited evidence describing the risk factors, laboratory features, and underlying mechanisms of this neurologic adverse event. We retrospectively reviewed available clinical, imaging, and laboratory data from adult patients with hematological malignancies who underwent haploidentical HSCT with cyclophosphamide (PTCy) at Chungnam National University Hospital from June 2016 to May 2020. Patients who developed LE were compared to those who did not based on clinical assessment, serum inflam-matory biomarkers, and reconstitution of various T cell populations. Of 35 patients, four devel-oped LE. There were no differences in patient demographics, donor demographics, or treatment conditions between patients that did and did not develop LE. Overall, patients with LE had worse clinical outcomes and overall survival than those without. In addition, they tended to have higher markers of systemic inflammation in the early post-transplant period, including fever, C-reactive protein (CRP), and cytokines. Remarkably, baseline interleukin-6 levels before HSCT were found to be higher in patients who developed LE than those who did not. In addition, analysis of T cell subsets showed impaired expansion of CD25+FOXP3+ regulatory T (Treg) cells in LE compared to non-LE patients despite appropriate reconstitution of the total CD4+ T cell population. Patients that developed LE within the first 30 days of HSCT were likely to have high serum IL-6 among other inflammatory cytokines coupled with suppression of regulatory T cell differentiation. Further work is needed on the mechanisms underlying impaired Treg expansion following HSCT and potential therapies.

The incidence of post transplantation lymphoproliferative disorders (PTLDs) and other neoplasms in organ transplant patients is higher than in the non-transplanted population. This event is more frequent in older subjects, due, at least in part, to the immune dysfunction induced by immunosuppressants administered to prevent rejection. Alterations of the immune system mechanisms of protection against carcinogenesis appear to be the key role in the in the pathogenesis of these neoplasms. The data of our study on the incidence of neoplasms occurred during a long-term follow-up in an elderly population after they underwent cardiac transplantation. This study gives, also evidence of the favorable effect of physical activity programs on cardiorespiratory and psychomotor function.

The treatment of critically ill patients remains an evolving and controversial issue. Mechanical circulatory support through a percutaneous approach for the management of cardiogenic shock has taken place in recent years. The combined use of IABP and Impella 2.5 device may have a role to play for this group of patients. A simulation approach may help with a quantitative as-sessment of the achievable degree of assistance. In this paper, we analyse the interaction be-tween Impella 2.5 pump applied as LVAD and IABP using the numerical simulator of the cardi-ovascular system developed in our laboratory. Starting with pathological conditions reproduced using literature data, the simulations were performed setting different rotational speeds for the LVAD and driving the IABP in full mode (1:1) or partial mode (1:2, 1:3 and 1:4). The effects in-duced by drug administration during the assistance were simulated too. The haemodynamic pa-rameters under investigation were: mean aortic pressure, systolic and diastolic aortic pressure, mean pulmonary arterial pressure, mean left and right atrial pressure, cardiac output, cardiac index, left and right ventricular end-systolic volume, left ventricular end-diastolic volume and mean coronary blood flow. The energetic variables considered in the study were: left and right ventricular external work and left and right atrial pressure-volume area. The outcome of our simulations shows that the combined use of IABP and Impella 2.5 achieves adequate support in the acute phase of cardiogenic shock compared to each standalone device. This would allow fur-ther stabilisation and transfer to a transplant centre should escalation of treatment be required.

Background and Objectives To compare navigator-gated three-dimensional T1-weighted gradient-echo sequences (NG-3D T1W-GRE) with standard breath-hold T1W-GRE (BH T1W-GRE) for the detection of HCC nodules in patients with chronic viral hepatitis which undergo at magnetic resonance imaging (MRI) using gadoxetic acid. Methods and materials We evaluated 58 patients with hepatic nodules at least 1 cm in diameter detected by ultrasound who underwent liver MRI including NG-3D T1W-GRE sequences and breath hold T1-weighted gradient-echo sequences with different flip angles(FA) at 10-25-40° after contrast administration of gadoxetic acid at magnetic scanner operating at1.5 Tesla. Image quality and relative hepatic and nodular enhancement were evaluated by three blinded reviewers. Results In these patients, image quality of NG-3D T1W-GRE was assessed significantly better than quality of BHT1W- GRE (P < 0.005) and relative enhancement was significantly higher than that of BH- T1W-GRE ( P

In this report, we present a study demonstrating how machine learning methods can reveal the interaction of different risk factors of post-transplant leukemic relapse and obtain robust predictions even with a modest clinical dataset. Using a cohort of 63 pediatric patients with acute lymphocytic leukemia (ALL) and 46 patients with acute myeloid leukemia (AML) who underwent stem cell transplant at a single institution, we built predictive models of leukemic relapse with both pretransplant and posttransplant patient variables (specifically lineage-specific chimerism) using the random forest classifier. The random forest classifier revealed different important predictive factors between ALL and AML in our relapse models consistent with previous knowledge. Furthermore, it also distinguished donor CD34 chimerism as most impactful in relapse prediction compare to donor chimerism of other cellular lineages in our dataset for ALL but CD3 for AML. Our models greatly improved sensitivity and specificity at predicting relapses in cross validation compared to a reference model based on our own institutional incidence of relapse and inferential statistical principles. Local Interpretable Model-Agnostic Explanations, an interpretable machine learning tool, confirmed our Random Forest Classification result and provided an intuitive explanation of how our machine learning models made the relapse prediction for each individual patient.

To analyze the effects of CYP3A5 polymorphism on liver function after LT and to characterize the pharmacokinetics of tacrolimus after conversion from a twice-daily regimen to a once-daily extended-release formulation. A prospective open-label study included 60 stable liver transplant recipients who underwent 1:1 conversion from twice-daily tacrolimus to once-daily tacrolimus. All participants were genotyped for CYP3A5 polymorphism. The study was registered at ClinicalTrials.gov (NCT 02882113). Twenty-eight patients were enrolled in the CYP3A5 expressor group and 32 in the non-expressor group. Although there was no statistical difference, incidence of liver dysfunction was higher in the expressor group than in the non-expressor group when converted to once-daily extended-release tacrolimus (P=0.088). No biopsy-proven acute rejection, graft failure, and mortality were observed in either group. The decrease in dose-adjusted trough level (- 42.9% vs. - 26.1%) and dose/kg-adjusted trough level of tacrolimus (- 40.0% vs. - 23.7%) was significantly greater in the expressor group than in the non-expressors after the conversion. The absorption of the tacrolimus in the non-expressor group was slower than in the expressors. In line with this observation, the AUC for once-daily tacrolimus correlated with Cmin in the non-expressors and Cmax in the expressors. Determination of CYP3A5 genotype in liver transplant recipients might be helpful in prediction of tacrolimus pharmacokinetics after conversion from a twice-daily regimen to a once-daily formulation.

Abstract: (1) Background: No consensus has been reached on indicators and protocols for monitoring drug concentrations in organ transplant recipients for the immunosuppressant mycophenolic acid (MPA) in clinical therapy.In this study, we propose to establish a Ultra Performance Liquid Chromatography–Tandem Mass Spectrometry (UPLC-MS/MS) for quantitative determination of MPA and its metabolites ( mycophenolic acid carboxybutoxyether, MPAG and mycophenolic acid carboxyglucuronide, AcMPAG) concentrations in peripheral blood mononuclear cells (PBMCs) and to assess the clinical application of PBMCs concentration detection of MPA and its metabolites in infection prediction in Chinese kidney transplant recipients(KTRs); (2) Methods: PBMCs were isolated with Ficoll-Paque solution, and cells were counted. Acetonitrile precipitated proteins to extract the target compounds.Waters ACQUITY UPLC BEH C18 column of 1.7μm (2.1 mm*50 mm) and an ACQUITY-Xevo TQ-S UPLC-MS/MS system were used for the detection with mobile phases: water and methanol (containing 2 mmol/L NH4Ac + 0.1% formic acid); flow rate: 0.3 mL/min. After gradient elution, the samples were positively ionized by an electrospray positive ion source (ESI) and then quantitatively analyzed by a triple quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode. The performance of the established method was evaluated through a series of validation experiments according to the requirements of the relevant guidelines. We enrolled 7 KTRs with stable conditions and 8 KTRs with infection from August to November 2022, who were treated at the West China Hospital of Sichuan University.Their peripheral blood samples were collected and detected MPA, MPAG, and AcMPAG concentrations in PBMCs using the methods mentioned above and evaluated for their clinical application in the prediction and monitoring of infections in KTRs; (3) Results: After validation of the methodology, the UPLC-MS/MS method established in this study for the determination of MPA, MPAG, and AcMPAG concentrations in PBMCs showed good linearity in the quantitative ranges of 0.0625-50 ng/ml, 0.5-50 ng/ml and 0.1-20 ng/ml, and the selectivity, specificity, matrix effect, carry-over contamination, reproducibility, precision and accuracy all satisfied the requirements.AcMPAG in PBMCs was poorly stabilized and showed significant degradation after -80°C storage for 24 h or 3 cycles of freeze-thaw.There was a large variability in MPA and MPAG concentrations in PBMCs of KTRs and it correlated poorly with plasma MPA concentrations (rs=0.206,p=0.117).Subgroup analysis showed that the correlation between MPA in plasma and PBMCs was still poor in the infected group(rs=0.201,p=0.116), but significant correlation in the stable group (rs=0.643,p=0.001). A significantly higher level of MPA in PBMCs was observed in the infected group than those in the stable group at 2h and 4h after drug dosing (p&lt;0.05).AcMPAG concentrations in PBMCs of KTRs were extremely low and virtually undetectable.ROC curve analysis (area under the curve, AUC) was performed for infection after renal transplantation with indicators of significant difference showed that the area AUC for PBMCs-MPA-C4 was 0.928 ,for PBMCs-MPA-C2 was 0.875,and for Plasma-MPA-C4 was 0.803; (4) Conclusions: In this study, a method based on UPLC-MS/MS was developed and validated for the simultaneous determination of MPA, MPAG, and AcMPAG concentrations in PBMCs.With easy operability and good stability, this method provides a reliable analytical method for the clinical implementation of the detection of MPA, MPAG, and AcMPAG concentrations in PBMCs.The concentrations of MPA and MPAG in PBMCs from KTRs were highly variable and were closely associated with the development of infections after renal transplantation.Monitoring MPA and MPAG in PBMCs may be useful indicators for mycophenolic acid therapeutic drug concentration monitoring (TDM) in KTRs.

OBJECTIVES: Most of human papilomavirus (HPV) infections are “cleared” by the immune system, however, in cases of immune system suppression infections could lead to development of malignancies. The aim of this study was to find out the frequency of HR-HPV infection in early period after renal transplantation in Latvian recipients receiving immunosuppressive therapy and to follow the progression of the infection up to one year. METHODS: 43 female renal recipients (median age of 48 IQR= 39-58) and 79 practically healthy female individuals (median age of 48 IQR= 42-57) as a control group were enrolled in this investigation. For the detection of HPV infection patients' samples (blood and vaginal swabs) where collected two weeks after transplantation with following collection of six months and one year. Different polymerase chain reactions for HR-HPV genomic sequences detection and commercial ELISA kit for detection of anti-HPV IgG antibodies were used. RESULTS: In this study we show that frequency rate of HR-HPV infection has increased by the one year after transplantation from early stage of immumosuppressive therapy (from 24% to 36%). Also increase of HR-HPV load was detected over the time, showing the highest median viral load at sixth month after transplantation. CONCLUSIONS: From the obtained data follows that it is very important to carefully monitor patients receiving immunosuppression therapy on progression of HR-HPV. In the case of this viral infection presence, immunosuppressive therapy must be attentively adjusted to avoid the HR-HPV infection rapid progression with the subsequent development of CIN or cervical cancer.

Heart transplantation (HT) is the gold standard therapy for advanced heart failure (AHF) and LVAD as destination therapy are an option in non-HT candidates. Most patients with AHF never receive a HT or a LVAD, so alternative strategies are needed. Intermittent levosimendan can reduce HF hospitalizations in AHF patients in the short term. It is uncertain whether the results of the comparison of inotropes with older generation LVAD would have the same outcomes in the current era of less sick but older, AHF treated with levosimendan patients. In this paper we compare the use of two therapeutic strategies for end-stage HF in patients not candidates for HT: Repetitive intermittent Levosimendan vs. LVAD as destination therapy. To do so we compare two multicentre cohorts of real-life patients from Spain: the LEVO-D Registry and the REGALAD registry. 715 patients coming from the 2 registries where found, 403 from the LEVO-D and 312 from the REGALAD. Non-adjusted median survival was shorter for LEVO-D patients; with the benefit for the LVAD seen only after the first year of therapy. The survival advantage for the LVAD cohort was also true after analysis of the matched cohort but, as in the non-matched analysis, the survival benefit was mainly shown after one year of follow up. We conclude that in elderly AHF non-HT-candidates, LVAD therapy offers significantly better long-term outcomes when compared to intermittent levosimendan; thus, it should be considered in carefully selected candidates. On the other hand, in poor LVAD candidates or highly comorbid patients, intermit-tent inotropic support with levosimendan could be a reasonable alternative to LVAD as 1-year outcomes are similar.

Hepatitis E virus is a major etiological agent of chronic hepatitis in immunosuppressed individuals. Studies on HEV in the context of liver transplantation have produced mixed results, most of the data coming from studies conducted in high-income countries. This was a prospective cohort study of liver transplant recipients in southeastern Brazil. Recipients were systematically followed for one year, with the objective of determining the prevalence, incidence, genotype, and natural history of HEV infection in this population. We included 107 liver transplant recipients and 83 deceased donors. Positivity for anti-HEV IgG was detected in 11 (10.2%) of the recipients and in eight (9.7%) of the donors. None of the patients tested positive for HEV RNA at baseline or during follow-up. There were no episodes of reactivation or seroconversion, even in cases of serological donor-recipient mismatch or in recipients with acute hepatitis. Acute and chronic HEV infections seem to be rare events in the region studied. That could be attributable to social, economic, and environmental factors. Our data indicate that, among liver transplant recipients, hepatitis E should be investigated only when there are elevated levels of transaminases with no defined cause, as part of the differential diagnosis of seronegative hepatitis after transplantation.

Background: Systemic treatment options for hepatocellular carcinoma (HCC) after liver transplantation (LT) are limited in patients in whom sorafenib treatment was failed. The purpose of our study was to compare outcomes among sorafenib, regorafenib, and nivolumab treatment groups in patients with recurrent HCC after LT. Methods: This study retrospectively evaluated patients who received sorafenib for recurrent HCC treatment after LT at a single center from March 2007 to December 2018. Some patients received regorafenib or nivolumab after sorafenib treatment failure. Results: Fifty-six patients were treated with sorafenib due to HCC recurrence. Among these, 38 patients (67.9%) continued treatment with sorafenib only; the other 18 patients (32.1%) were converted to regorafenib treatment. Ten patients (17.9%) of these 18 were converted to nivolumab after sorafenib and regorafenib therapy failed. The disease-free survival and overall survival (OS) from LT were not different among the three groups. In addition, OS from HCC recurrence, sorafenib usage, and usage of each systemic therapeutic agent were not different among the three groups. Three cases in the nivolumab group developed acute rejection; one of these led to graft failure and death due to antibody-mediated rejection. Conclusion: Sequential regorafenib or nivolumab treatment in recurrent HCC LT patients does not improve OS compared sorafenib treatment.

Background: Delayed graft function (DGF) is common after kidney transplantation from de-ceased donor and may significantly affect post-transplant outcomes. This study aimed to evaluating whether an innovative approach, based on the administration of intravenous prostaglandin-analogue iloprost, could be beneficial in reducing the incidence of DGF occurring after kidney transplantation from deceased donors. Methods: This prospective, randomised (1:1), place-bo-controlled study enrolled all consecutive patients who received a kidney transplantation from a deceased donor from January 2000 to December 2012 and who were treated in the peri-transplant period with the prostaglandin-analogue iloprost at 0.27 μg/min through elastomeric pump (treatment group) or placebo (control group). Results: A total of 476 patients were included : DGF was reported in 172 (36.1%) patients in the entire cohort. The multivariate analysis showed that donor’s age > 70 years (OR 2.50, 95% Confidence Interval (CI) 1.40-3.05, p < .001), cold ischemia time > 24 h (OR 2.60, 95 CI 1.50-4.51, p < .001), donor’s AKI (OR 2.71, 95% CI 1.61-4.52, p = .021) and, above all, recipient’s arterial hypotension (OR 5.06, 95% CI 2.52-10.1, p < .0001) were the strongest risk factors for developing post-transplant DGF. The incidence of DGF was 21.4% in the treatment group and 50.9% in the control group (p< .001). Interestingly, among patients who developed DGF, those who received iloprost had a shorter duration of post-transplant DGF (10.58.3 v s13.46.7, days, p= .016). Conclusions: This study showed that the use of a continuous infusion of iloprost could safely and effectively reduce the incidence of DGF in recipients of deceased donor kidneys, allowing a better graft functionality as well as a better graft survival.

RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) is shown to block replication of the SARS-CoV-2 virus and has been granted Fast Track Designation by the US FDA for the treatment of Critical COVID-19 with Respiratory Failure. We describe the clinical course of the first patient treated with this investigational medication in an open label manner -- a 54 year old patient suffering antibody-mediated rejection of his double lung transplant who contracted COVID-19 with respiratory failure refractory to all currently available therapies. He received three infusions of RLF-100 under an FDA-approved emergency use IND. Within 24 hours of the third infusion, substantial improvement in oxygen saturation and radiographic improvement in characteristic COVID-19 pneumonitis was noted. He was discharged from intensive care at that point and scheduled for discharge to home at 1 week on room air. Despite an intervening hospitalization for trauma, he remains alive and free of respiratory failure at 28 days post treatment.

Rehabilitation following anterior cruciate ligament reconstruction with hamstring graft allows the patient to regain his functional capacities and to support him in the resumption of sports activities. Rehabilitation also aims to minimize the risk of recurrence, which is why it ensures that the patient's muscular capacities develop properly until they return to sport. Isokinetics helps strengthen and assess the strength of muscle groups in the thigh, but controversy exists as to its use by resistance to the open kinetic chain knee extension that would cause the transplant to distend. The objective of this study is to determine the influence of isokinetic muscle strengthening on the possible laxity of the anterior cruciate ligament and to be able to determine risk factors. The study relates to a population having benefited from anterior cruciate ligament reconstruction with hamstring graft from 3 to 6 months after surgery. Two groups are differentiated, one group exposed to isokinetism during rehabilitation, the other group, named unexposed, undergoes rehabilitation without the use of isokinetism. An anterior knee laxity test is performed 6 months postoperatively using the GNRB® machine for all subjects according to the same protocol. The test results were statistically analyzed to determine a relative risk of transplant distension for each group in the study. Comparison of the results of each group by univariate analysis did not reveal any significant result. Multivariate analysis showed interactions in the two strata of the study. It was argued that the use of isokinetics seems to have no effect on the risk of developing distension for the majority of subjects in the exposed group. A tendency towards transplant protection was perceived for each variable except the age under 25 years (RRa = 1.07). The use of isokinetics does not appear to be a cause of transplant distension in patients undergoing an anterior cruciate ligament reconstruction when this method is introduced 3 months postoperatively.

The incidence of cancer in organ transplant patients is higher than in the non-transplanted population. The incidence increases with increasing age. The use of Fludeoxyglucose positron emission tomography/CT (PET/CT) is sensitive and specific to detect PTLD LD compared with conventional CT imaging. We analyzed the medical data of 127 patients aged over 60 years, who underwent heart transplantation in the above period, who have been practicing early CT-PET for diagnostic purposes between February 2007 and October 2018. Of 127 consecutive patients who underwent CT-PET, SUVs up than 4, were found in 84 patients of which 20 were affected by PTLDs, seven patients were affected by chronic non neoplastic inflammatory diseases, the remainder were affected by other neoplasms. The favorable effect of physical activity programs on cardiorespiratory and psychomotor function occur in all patients. In conclusion, CT-PET at the first doubts about the possibility of the development of neoplasms has allowed a diagnosis and then a treatment more quickly. Education in behavioral norms that improve the patient's quality of life is necessary.

Pre-exposure prophylaxis for COVID-19 with Tixagevimab/Cilgavimab in immunocompromised patients has reduced the risk of breakthrough infection, disease, hospitalization, and COVID-19 related mortality. However, the advent of the Kraken variant (XBB.1.5) has limited the use of this monoclonal antibody, based on poor efficacy in in vitro studies The objective of the study was to evaluate the risk of breakthrough infection, symptomatic disease, hospitalization, intensive care admission and COVID-19 related death in kidney transplanted recipients receiving pre-exposure prophylaxis with Tixagevimab/Cilgavimab for COVID-19 in the era of the Kraken variant (XBB.1.5). In a prospective, observational study, we enrolled kidney transplant patients undergoing pre-exposure prophylaxis for COVID-19 with Tixagevimab/Cilgavimab at the Division of Infectious Diseases of Federico II University of Naples between February 2023 and August 2023. Each patient subsequently underwent a six-month follow-up with symptom monitoring and surveillance nasopharyngeal swab for SARS-CoV-2 RNA detection every 30 days, regardless of symptoms. Thirty-four kidney transplant patients were enrolled and in the follow-up period, only one tested positive for the nasopharyngeal swab for SARS-CoV-2 research with asymptomatic infection and virological recovery on the eighth day from the diagnosis of infection. Therefore, no patient developed disease and no patient needed hospitalization and no death occurred. No adverse drug reaction to Tixagevimab/Cilgavimab occurred. Our data, although derived from a limited and uncontrolled sample, show the potential of Tixagevimab/Cilgavimab as a valid and viable therapeutic strategy in pre-exposure prophylaxis for immunocompromised patients. These findings highlight the importance of conducting clinical studies on this topic.

Abstract: Background: Irreversible electroporation (IRE) is a form of non-thermal ablation that delivers pulses of high voltage electrical current between electrodes. The role of IRE in the treatment of colorectal hepatic metastases is unestablished. This study is an international ques-tionnaire survey of the use of IRE for colorectal hepatic metastases. Methods: A questionnaire addressing views on the use of IRE for colorectal liver metastases was circulated to clinicians with an interest and/or expertise in this technique. Results: 64 clinicians from 17 different countries replied to the questionnaire. Thirty-six (56%) had experience of treating patients with colorectal liver metastases with IRE. The preferred mode of delivery of IRE was percutaneous treatment under CT guidance. Thirty-three (70% respondents) used IRE exclusively for lesions in proximity to inflow or outflow structures. Twenty (43% respondents) used IRE as their sole ablative treat-ment whilst 19 (40% respondents) used IRE in combination with thermal ablation. The maximum number of lesions that could be treated by IRE was two and preferred size of lesion was

The diagnosis and management of cow's milk allergy (CMA) is a topic of debate and controversy. We aimed to compare the opinions of expert groups from the Middle East (n=14) and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (n=13). These Expert groups voted on statements developed by the ESPGHAN group and published in a recent position paper. The voting outcome was compared. Overall, there was consensus amongst both groups of experts. Most experts agreed that symptoms of crying, irritability and colic, as single manifestations, do not suggest CMA. They agreed that amino-acid-based formula (AAF) should be reserved for severe cases (e.g. malnutrition and anaphylaxis) and that there is insufficient evidence to recommend a step-down approach. There was no consensus on the statement that a cow’s milk-based extensively hydrolysed formula (eHF) should be the first choice as a diagnostic elimination diet in mild/moderate cases. Although the statements regarding the role of hydrolysed rice formula as a diagnostic and therapeutic elimination diet were accepted, 3/27 disagreed. The votes regarding soy formula highlight the differences in opinion in the role of soy protein in CMA dietary treatment. Generally, soy-based formula is seldom available in the Middle East region. All ESPGHAN experts agreed that there was no added value of probiotics, prebiotics, and synbiotics to the efficacy of elimination diets, whereas 3/14 of the Middle East group thought there was sufficient evidence. Therefore, there is not a consensus on the optimal diagnostic and therapeutic elimination diet for CMA, but the first-choice elimination diet and the stepwise management approach reveal some differences.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.

The Simultaneous Localization And Mapping (SLAM) scanner is an easy and portable Light Detection And Ranging (LiDAR) data acquisition device. Its main output is a 3D point cloud covering the scanned scene. Regarding the importance of accuracy in the survey domain, this paper aims to assess the accuracy of two SLAM scanners: the NavVis VLX and the BLK2GO Scanner. This assessment is conducted for both outdoor and indoor environments. In this context, two types of reference data are used: the Total Station (TS) and the static scanner Z+F Imager 5016. To carry out the assessment, four comparisons are tested: cloud to cloud, cloud to mesh, mesh to mesh, and edge detection board assessment. However, the results of the assessments confirm that the accuracy of indoor SLAM scanner measurements (5 mm) is greater than that of outdoor ones (between 10 mm and 60 mm). Moreover, the comparison of cloud to cloud provides the best accuracy regarding direct accuracy measurement without manipulations. Finally, based on the high accuracy, scanning speed, flexibility, and the accuracy differences between tested cases, it is confirmed that SLAM scanners are effective tools for data acquisition.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Superior fiber quality is one of the most important objectives in cotton breeding. To detect the genetic basis underlying fiber quality, an F2 population containing 413 plants was constructed by crossing Jifeng 914 and Jifeng 173, both of which have superior fiber quality, with Jifeng 173 being better. Five fiber quality traits were investigated in the F2, F2:3, F2:4, and F2:5 populations. Quantitative trait loci (QTL) mapping was conducted based on a high-density genetic map containing 11,488 single nucleotide polymorphisms (SNPs) and spanning 4,202.12 cM in length. Transgressive segregation patterns and complex correlations in the five tested traits were observed. A total of 108 QTLs were found, including 27 for fiber length (FL), 16 for fiber strength (FS), 24 for micronaire (MC), 17 for fiber uniformity (FU), and 24 for fiber elongation rate (FE). Chromosome A7 contained 12 QTL, ranking the first. No QTL was found on chromosome D1 and D11. Each QTL contributed 1.98%–21.45% to the phenotypic variation (PV), including 13 major effect QTLs that contributed more than 10% toward PV. Two QTLs could be repeatedly detected in three populations, including qFL-D3-2 in F2, F2:4, and F2:5 with 9.18%–21.45% of PV, qFS-A11-1 in F2:3, F2:4 and F2:5 with 6.05%–10.41% of PV. Another seven stable QTLs could be detected in two populations, including four major effect QTLs: qFL-A12-3, qFS-D10-2, qMC-D6-2, and qMC-D8-1. Fourteen QTL-overlapping regions were found, which might explain the complex correlations among the five phenotypic traits. Four regions on chromosome A11, D3, D6, and D10 covered by both stable and major effect QTLs are promising for further fine mapping. The genomic regions of the two QTLs detected in three populations and the four major effect QTLs contain 810 genes. Gene functional analysis revealed that the annotated genes are mainly involved in protein binding and metabolic pathways. Fifteen candidate genes in the qFL-D3-2 region are highly expressed in fiber or ovules during fiber initiation, elongation, secondary cell wall thickening, or maturation stages. qRT-PCR revealed that Ghir_D03G005440.1 and Ghir_D03G011310.1 may play a role in promoting fiber initiation, Ghir_D03G006470.1 may be beneficial for promoting fiber elongation. This study provides more information for revealing the molecular genetic basis underlying cotton fiber quality.

Currently there are fewer depth models applied to pepper picking detection, while the existing generalized neural networks have problems such as large model parameters, long training time, and low model accuracy.In order to solve the above problems, this paper proposes a Yolo-chili target detection algorithm for chili pepper detection. First, the classical target detection algorithm yolov5 is used as a benchmark model, and an adaptive spatial feature pyramid structure combining the attention mechanism and the idea of multi-scale prediction is introduced to improve the model's detection effect on occluded peppers and small target peppers. Secondly, a three-channel attention mechanism module is introduced to improve the algorithm's long-distance recognition ability and reduce the interference of redundant testers. Finally, the quantized pruning method is used to reduce the model parameters and realize the lightweight processing of the model. Applying the method to the homemade chili pepper dataset, the AP value of chili pepper reaches 93.11%; the accuracy rate is 93.51% and the recall rate is 92.55%.The experimental results show that yolo-chili is able to achieve accurate and real-time pepper detection under complex orchards.

The temporary immersion system bioreactor named GreenTray®[2], [3]presents advantages over the existing ones. Firstly, there is no need to use forceps to move the shoots or plantlets in or out of the recipient, neither the use of scalpel to divide them. Secondly, the basis of the shoot can remain in the GreenTray® and can sprout again in several cycles of growth. These two characteristics reduce the costs in the process of micropropagation. Besides, shoots or plantlets development is enhanced by the aeration of the recipient, thus enriching with CO2 the recipient atmosphere. The chapter describes and provides images and values of interest in (1) the micropropagation process of some commercial Prunus or Pyrus rootstocks; (2) the plantlet growth under autotrophic conditions; and (2) the inoculation of plants with pathogens that reproduce in vitro the symptoms observed in vivo, using the GreenTray® bioreactor.

Aiming at the problems of inaccurate segmentation of long object and information loss of small object in real-time semantic segmentation algorithm, this paper proposes a lightweight multi-branch real-time semantic segmentation network based on BiseNetV2. The new auxiliary branch makes full use of spatial details and context information to cover the long object in the field of view. Meanwhile, in order to ensure the inference speed of the model, the asymmetric convolution is used in each stage of the auxiliary branch to design a structure with low computational complexity. In the multi-branch fusion stage, the alignment and fusion module is designed to provide guidance information for deep and shallow feature mapping, so as to make up for the problem of feature misalignment in the fusion of information at different scales, and thus reduce the loss of small target information. In order to further improve the model’s awareness of key information, a global context module is designed to capture the most important features in the input data. The proposed network uses NVIDIA GeForce RTX 3080 Laptop GPU experiment, on the road street view data set Cityscapes and CamVid average occurring simultaneously ratio reached 77.1% and 78.4% respectively, with running speed of 127 frames/s respectively and 112 frames/s. The experimental results show that the proposed algorithm can achieve real-time segmentation and improve the accuracy significantly, showing good semantic segmentation performance

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

In this paper we study a class of impulsive delayed neural networks with parameter uncertainties and reaction-diffusion terms. Using the properties of M-matrices and some inequality techniques, some sufficient conditions are derived to guarantee the global exponential stability of the given system. The results obtained are presented by simple algebraic inequalities, which are certainly more concise than previous methods. Finally, the validity and usefulness of our results are illustrated by arithmetic examples.

Pyrops candelaria is one of the common pests of fruit trees, but the research on the pathogenic microorganisms it may carry is very limited. Therefore, it is essential to reveal the pathogenic microbes it carries and their potential hazards. This study found a new virus from the transcriptome of P. candelaria, which was first reported in P. candelaria and named as PyCaV (Pyrops candelaria associated virus). RACE and bioinformatics assay revealed that the full-length of PyCaV is 10855 bp with the polyA tail, containing a single open reading frame (ORF) encoding a polyprotein consisting of 3171 amino acid (aa). The virus has a typical Iflavirus structure, including two rhv domains, a RNA helicase domain (HEL), a 3C cysteine protease domain (Pro), and a RNA-dependent RNA polymerase domain (RdRp). Further phylogenetic analysis revealed that this virus belongs to family Iflaviridae and sequence alignements analysis suggedted PyCaV is new member in unassigned genus of family Iflaviridae. Further in-depth analysis of virus-infection-part showed that PyCaV is distributing in the whole longan lanternfly, including its head, chest, and abdomen, but more PyCaV was identified in the chest. The distribution of PyCaV in different parts of P. candelaria was further explored, which showed that more PyCaV were detected in its piercing-sucking mouthparts and chest viscera. Statistical analysis showed that the PyCaV infection was affected by time and locations.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p &lt; 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

With the burgeoning growth of online retail, the issue of counterfeit products has become a significant threat to both consumer trust and brand integrity, posing challenges to sustainable market practices. Online retail platforms are promoted to redesign their channel structures and enhance brand traceability to tackle counterfeits using blockchain technology. To investigate the interactions between blockchain technology and the channel structures of online retail platforms, we design a game theory model incorporating a manufacturer with(out) blockchain participation selling products via an online retail platform that operates an agency channel and/or a reselling channel. We show that the critical trade-off of blockchain participation comprises the brand assurance effect of the blockchain, the channel competition intensification effect, and the blockchain adoption cost. The platform is capable of strategically designing the channel structure to encourage (while discouraging) blockchain participation by the manufacturer. Our analysis highlights the complementarity between blockchain participation and the channel structure. Furthermore, the effect of the consumer’s belief in the reselling channel, the commission fee in the agency channel, and the substitutability between channels are investigated in depth. The research provides valuable insights for online retail platforms and policymakers seeking to foster a sustainable and trustworthy e-commerce ecosystem.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

The properties of the annual, semiannual and triennial oscillations (AO, SAO and TO) in the middle atmosphere have been investigated using the TIMED/SABER temperature data. The Lomb-Scargle and wavelet spectra were used to determine the dominant oscillations in the background temperature field. The AO is prominent at the mid-latitudes. The AO amplitudes present an asymmetry between the two Hemispheres, being larger in the mesosphere than in the stratosphere. The SAO dominates the tropical regions, with three amplitude maxima at altitudes of 45, 75, and 85 km. The SAOs in the upper mesosphere (75 km) are out of phase with those in the mesopause (85 km) in the tropical regions, which can generate an enhancement of 11 K at each equinox, contributing to the lower mesospheric inversion layer. The TO is significant in the tropical region, with amplitude being maximum at 35, 45 and 85 km. Result shows that there may be potential interaction by the TO with SAO at 85km at the equator. The relation between ENSO and TO has also been discussed. The ENSO signal may modulate the amplitude of the TO, mainly in the lower stratosphere. The real origin of the TO may lie in the wave-mean-flow interaction.

The paper describes the new method for image compression based on coordinated group signal transformation. The algorithm is a type of difference coding. Coordinated processing significantly simplifies the difference signal conversion scheme using a single group codec for all signals. The described method considers color channels as correlated signals of a multi-channel communication system. The specifics of the processed data required modification of the coordinated group processing algorithm. First, we changed how to calculate the difference signals to prevent data loss. Secondly, the group codec was supplemented with a neural network to improve the quality of reconstructed images. We considered the following types of neural networks: fully connected, recurrent, convolution, and convolution in the Fourier space. Based on the simulation results, it is best to use fully connected neural networks if the goal is to minimize processing delay time. These networks have a response time of 13 ms. On the other hand, if the priority is to improve quality in cases where delays are not critical, then convolution neural networks in the Fourier space should be used. These networks have a response time of 140 ms and are of significant interest.

As the world population grows, fulfilling the need for biomaterials in the healthcare system becomes increasingly important. Biomaterials, which include metals, polymers, ceramics, and composites, play an important role in the creation of medical devices that improve people's lives. The European Society for Biomaterials described biomaterials as non-biological materials used in medical devices to interact with biological systems. This definition has developed to encompass materials that treat, assess, or replace tissues or bodily functions. Biocompatibility, as defined by the FDA, is a key feature of biomaterials, as is the requirement to fulfil design requirements such as mechanical performance, geometry, and electrical control. Over the last decade, advances in regenerative medicine and tissue engineering have boosted biomaterials' usage in medical applications dramatically. Despite its promise, scientists, engineers, and physicians continue to face significant challenges due to the complexity of biomaterials. Biomaterials have various benefits, including biodegradability, non-toxicity, and biocompatibility, making them extremely useful for replacing, sustaining, or improving biological activities in damaged tissues. They are used in a wide range of applications, including tissue engineering implants, human tissue healing and regeneration, medication delivery systems, and biosensors. This study gives insights into the fundamental characteristics, case studies, and ethical issues associated with the usage and use of biomaterials, further examining their potential and significance in healthcare and medicine.

The studied solar pot is a recent invention, which gained a utility model protection in 2021 from the Hungarian Intellectual Property Office under patent number 5489. The device is made for environmentally friendly cooking or heating (by utilizing solar energy) of foods and liquids. Its structure is similar to a double pipe heat exchanger, it has an outer mantle and an inner cooking tank. The goals of the paper are proposing a new physically-based mathematical model describing the solar pot and carrying out computer experiments with it, assembling an experimental system of the pot connected with a solar collector and performing measurements on it. Based on the results, the solar pot can successfully be used for cooking or sterilizing foods or liquids during the studied time period, in Hungary.

The research reported on this paper was aimed at improving the overall efficiency of a PDO certified artisanal cheese production process. Being a PDO certified foodstuff by the EU, it is considered to have properties and qualities determined by the geographical environment in which is made, with its production taking place in a specific and determined geographical location, in this case the Serra da Estrela region. In that sense, the authors conducted a mapping according to a systemic perspective of the processes involved in the context of manufacturing and distribution of certified Serra da Estrela cheese. Numerous methods were used throughout the process, such as a systemic design analysis, and techniques derived from ethnographic methods, which led to the collection of data in the field and consequently provided the immersion of the researcher in genuine work situations. Critical points were identified and emphasized in the systemic map with the purpose of encouraging initiatives to address and overcome the gaps and inefficiencies detected. The systemic design analysis triggered the development of design work. Observations following an ethnographic approach identified ergonomic risks in cheese making during the process of cutting excess chips, fostering the emergence of musculoskeletal disorders at the wrist. A tool that fits best to the task at hand was developed. A prototype of the new tool enabled collecting feedback from use in the work context, in order to inform product development. The domains of agricultural production and microbiology, considering the specific microorganisms developed trough the ripening process of the cheese, turned out to be aspects of high importance for the issue under focus, contributing to a broader understanding of the ripening process and its risks, simultaneously improving the efficiency and success of cheese production. If it were not for the systemic analysis, which served as a link between the boundaries of distinct domains such as the risk of microorganism contamination, ergonomics, energy efficiency, legislation and regulation policies, transportation challenges and economic viability, approached throughout the research. Simultaneously creating bridges between them, the various problems might not have been detected in the first place, as they are usually addressed in specialized disciplines, predetermined by the restrictions of each specific area of knowledge. As a consequence of the development of this research, which was based on an analysis that sought to establish possible connections between various disciplines and tried to constantly maintain a holistic perspective, making new connections and observing the issues from a new angle, apart from the already established methodologies. All this allowed to lay out the seeds for the development of a plan to tackle the critical points identified by the systemic analysis reported in this paper.

Abstract: Transcription factors are crucial pre-transcriptional regulatory mechanisms that can modulate the expression of downstream genes by binding to their promoter regions. DOF (DNA binding with One Finger) proteins are a unique class of transcription factors with extensive roles in plant growth and development. Our previous research indicated a decrease in iron content in chlorotic bamboo leaves. However, to our knowledge, genes related to iron metabolism pathways in bamboo species have not yet been studied. Therefore, in the current study, we identified iron metabolism-related (IMR) genes in bamboo and determined the transcription factors that significantly influence them. Among these, DOFs were found to have widespread effects and potentially significant impacts on their expression. We identified specific DOF members in Dendrocalamus latiflorus with binding abilities through homology with Arabidopsis DOF proteins, and established connections between some of these members and IMR genes using RNA-seq data. Additionally, molecular docking confirmed the binding interactions between these DlDOFs and the DOF binding sites in the promoter regions of IMR genes. The co-expression relationship between the two gene sets was further validated using q-PCR experiments. This study paves the way for research into iron metabolism pathways in bamboo and lays the foundation for understanding the role of DOF transcription factors in D. latiflorus.

This paper is focused on typical rural settlements in the Stara Planina Mountain area in Serbia. They are distinguished by their authenticity, identity and character, and they have still not been destroyed by inappropriate development as is the case in some other mountain areas in Serbia, where the effects of urbanization, globalization and homogenization are obvious. Consequently, there is a need to prevent these effects in mountain areas where there is a threat of disbalance between development and the inherited natural and cultural values. The paper starts from several important concepts that relate contemporary approaches to cultural heritage preservation, place morphology and planning future development. The concept definitions from recent documents from related fields are used. These concepts are then applied to the area of Stara Planina Mountain and its rural settlements. The necessity for an integrative approach to planning this area with significant natural and anthropogenic potential is pointed out, including its integration into international programs of sustainable development.

The wetlands in northeastern Bangladesh are home to some of the most prolific and valuable ecosystems on the planet, offering a wide range of benefits to both the local and wider communities. A limited number of research on this topic have been carried out in various wetlands in coastal hilsa, but none have been located in the northeastern region of Bangladesh. Thus, the goal of this study was to better understand the most commercially relevant species (anadromous hilsa) in northeastern Bangladesh as well as to assess the wetland ecosystem services more thoroughly with the contribution of their fish genetic resources. In addition to laboratory studies, fieldwork was done in the fishing settlements along the Surma River, Hakaluki Haor, and Tanguar Haor. The study classified 77 fish species into 21 subcategories of ecosystem services, of which 56% were not threatened, 17% were vulnerable, and 10% were highly endangered. The species Hilsa was found to be the most economically significant, accounting for 1% of the GDP overall. The study determined if the hilsa stock of the examined wetlands maintains a single or several subpopulations in comparison to other parts of the country when they migrate from saline water to northeastern Bangladesh (freshwater). But when compared to other groups, the FST score was between 0.000 to 0.017, indicating that the populations are identical and that there is genetic material sharing between them. Additionally, these statistics imply that the Sylhet haor and adjacent river systems contain a single stock of Hilsa fish. Nevertheless, a number of stresses and risks, including overexploitation, illicit and destructive fishing, siltation, and natural disasters like flash floods, have been linked to changes in the supply of hilsa and other ecosystem services. This study also emphasizes the necessity of policy attention and research to address the concerns.

The continuous casting process of helical fiber reinforced metal matrix composites was proposed, and the experimental equipment was designed and manufactured. The relationship model be-tween the process parameters and the helical shape of the fibers in the metal matrix is analyzed by differential geometry. Helical carbon fiber reinforced lead matrix composites were prepared under different conditions. When the melting temperature and cooling intensity were increased, the helical radius of helical carbon fiber in lead matrix was increased. When the fiber rotation speed was increased, the helical radius was decreased, and the helical pitch was de-creased proportionally. The experimental results are consistent with the process model. Carbon fiber rein-forced aluminum composites were prepared. Scanning electron microscopy showed that the infiltration between the aluminum matrix and the carbon fiber was not complete. As the volume fraction of carbon fiber which was added in composites is too small, the mechanical properties of the composites have not been significantly improved.

This article presents an innovative approach to the design of a safe adaptive backstepping control system. Tailored specifically for underactuated marine robots, the system utilizes simple sensors for enhanced practicality and efficiency. Given their operation in diverse oceanic environments fraught with various sources of uncertainties, ensuring the system's safe and robust behavior holds paramount importance in the control literature. To address this concern, this paper introduces a control strategy designed to ensure robustness at both the kinematic and dynamic levels. By emphasizing the compensation for the system uncertainties, the design integrates a straightforward fuzzy system structure. To further ensure the system's safety, a funnel surface is defined, followed by the design of a suitable nonlinear sliding surface as a function of the funnel and tracking error. Specifically leveraging the Lyapunov function, the study formally establishes the Semi-globally Practically Finite-time Stability of the closed-loop system, validated through simulations conducted on underactuated marine robots.

Several types of guided bone regeneration materials are available with various properties and clinical indications. Among them, dentin-derived matrix from extracted teeth is an excellent alternative to traditional graft materials, such as allografts and xenografts. Different clinical preparation protocols exist: block form versus powder form, demineralized versus non-demineralized form. Out of these methods, demineralization protocols for dentin-derived matrix from extracted teeth have been noted for a wide range of successful clinical outcomes. The purpose of this animal study was to find out the most effective method of demineralizing dentin-derived matrix to result in the highest regenerative ability in the bone graft material in rabbit calvaria. The study conducted a comparative histomorphometric analysis of four groups in distinguished matrix conditions: a control group without graft placement, a non-demineralized dentin-derived matrix graft placement group, a 15-minute demineralized dentin-derived matrix graft placement group, and a 30-minute demineralized dentin-derived matrix graft placement group. Regenerative processes were evaluated three times at 2, 4, and 8 weeks post-graft placement. These groups of rabbits were evaluated randomly in a blinded setting to prevent bias. Among the four groups compared, the group with a 15-minute demineralized dentin-derived matrix graft showed the most efficient bone regeneration in the histomorphometric analysis. Based on this animal study, it was apparent that a 15-minute demineralization of dentin-derived matrix is the preferred preparation protocol to maximize the regenerative potential in the matrix.

Promoting green development has become an important way to optimize the ecological and economic structure and promote sustainable development. The Yangtze River Economic Belt is an important economic corridor in China, and it remains to be examined whether the implementation of environmental regulations has enhanced the green total factor productivity (GTFP) of cities. This paper calculates the green total factor productivity of 107 cities within the Yangtze River Economic Belt by using the super-efficient SBM model and the GML index with Chinese city panel data from 2007-2019 and measures the intensity of environmental regulations through textual analysis. The bidirectional fixed-effects model constructed in this paper suggests an inverted U-shaped relationship between environmental regulation and GTFP, which is confirmed by a series of robustness tests. Green technology innovation and advanced industrial structure play a mechanism role in this. In regions with lower levels of green technology and industrial structure, the inverted U-shaped relationship between environmental regulation and green total factor productivity is more significant. In addition, the phenomenon of GTFP rising and then falling because of environmental regulation is more obvious in cities in the middle and upper reaches of the Yangtze River and outside the urban agglomerations. Therefore, when formulating environmental regulation policies, it is necessary to balance the relationship between economic development and environmental protection and harmonize the environment and economic development of the entire Yangtze River Basin.

Cocoa (Theobroma Cacao, L.) represents an important market that gained relevance and became an esteemed commodity thanks to cocoa powder, chocolate, and other related products. This work has analyzed 59 cocoa powder samples from the European market. Three distinct subgroups were identified: organic or conventional, alkalized or not alkalized, and raw or roasted processing. The impact of the technological process was evaluated on the pH, color, and compositional traits, as content of biogenic amines and salsolinol. The phenolic fraction was also investigated trough both common and emerging methods. Results depict that the influence of the agronomical practices (organic/conventional) did not affect significatively (p&lt;0.05) the composition of cocoa powders; similarly, the roasting process was not discriminative for the compounds traced. On the other hand, the alkalinization process greatly impacted on color, and pH, no matter of cocoa provenience, obtention, or other processes, also resulting reducing the phenolic fraction of treated samples. Principal components analysis confirmed that the alkali process acts on pH, color, and phenolic composition, but not on other bioactives molecules (BAs and salsolinol). All samples resulted safe while alkalized powders have a great reduction in beneficial biocompounds. A novel strategy could be to emphasize non-alkalized powders in the label, to meet the demand for more beneficial products.

Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy, with mortality rates that reach 60%, mainly due to an excessive diagnostic delay. MiRNAs, a class of crucial epigenetic gene-expression regulators, have emerged as potential diagnostic biomarkers, with >200 molecules reported to be dysregulated in OSCC. We had previously established an in silico methodology for the identification of the most disease-specific molecules by bridging genetics and epigenetics. Here, we identified the stage-specific miRNAs that govern the asymptomatic early stages of oral tumorigenesis by exploiting the reverse interplay between miRNA-levels and their target-genes’ expression. Incorporating gene expression data from our group’s experimental hamster model of sequential oral oncogenesis, we bioinformatically detected the miRNAs that simultaneously target/regulate >75% of the genes that are characteristically upregulated or downregulated in the consecutive stages of hyperplasia, dysplasia and early-invasion OSCC, while exhibiting the opposite expressional dysregulation in OSCC-derived tissue and/or saliva specimens. We found that all stages share the downregulation of miR-34a-5p, miR124-3p, and miR-125b-5p, while miR-1-3p is underexpressed in dysplasia and early-invasion. Malignant early-invasion stage is distinguished by the downregulation of miR-147a and the overexpression of miR-155-5p, miR-423-3p and miR-34a-5p. The identification of stage-specific miRNA molecules may facilitate their utilization as biomarkers for presymptomatic OSCC diagnosis.

Estimating the ocean’s subsurface thermohaline information from satellite measurements is essential for understanding ocean dynamics and El Niño phenomenon. This paper proposes an improved double-output Residual Neural Network (DO-ResNet) model to concurrently estimate the ocean subsurface temperature (OST) and ocean subsurface salinity (OSS) in the tropical Western Pacific using multi-source remote sensing data, including sea surface temperature (SST), sea surface salinity (SSS), sea surface height anomaly(SSHA), sea surface wind (SSW), and geographical information (including longitude (LON) and latitude (LAT)). In the model experiment, Argo data were used to train and validate the model, and the root mean square error (RMSE), normalized root mean square error (NRMSE) and coefficient of determination (R²) were employed to evaluate the model's performance. The results showed that the sea surface parameters selected in this study have a positive effect on the estimation process, and the average RMSE and R² values for estimating OST (OSS) by the proposed model are 0.34 °C (0.05 psu) and 0.91 (0.95), respectively. Under the data conditions considered in this study, DO-ResNet demonstrates superior performance relative to the extreme gradient boosting model, random forest model, and artificial neural network model. Additionally, this study evaluates the model’s accuracy by comparing its estimations of OST and OSS across different depths with Argo-derived data, demonstrating the model's ability to effectively capture the most spatial features, and by comparing NRMSE across different depths and seasons, the model displays strong seasonal adaptability. In conclusion, this research introduces a novel artificial intelligence technique for estimating OST and OSS in the tropical Western Pacific Ocean.

The normal growth and development of skeletal muscle is essential for the health of the body. The regulation of skeletal muscle by intestinal microorganisms and their metabolites has been continuously revealed. Acetate is the predominant short-chain fatty acid synthesized by gut microbiota through the fermentation of dietary fiber, however, the underlying molecular mechanisms governing the interaction between acetate and skeletal muscle during rapid growth stage remain to be further elucidated; Here, specific pathogen-free (SPF) mice, germ-free (GF) mice, and germ-free mice supplemented with sodium acetate (GS) were used to evaluate the effects of acetate on skeletal muscle growth and development of young mice with gut microbiota deficiency; We found the concentration of serum acetate, body mass gain, succinate dehydrogenase activity and expression of myogenesis maker gene of skeletal muscle in the GS group was higher than GF group following sodium acetate supplement. Furthermore, the transcriptome analysis revealed that acetate activated biological processes regulating skeletal muscle growth and development in GF group that are inhibited due to gut microbiota deficiency. In vitro experiment, we proved that acetate up-regulated Gm16062 to promote skeletal muscle cell differentiation; Overall, our findings proved that acetate promote skeletal muscle growth and development in young mice via increase Gm16062 expression.

Phased injection of natural gas into internal combustion marine engines is a promising solution for optimizing performance and reducing harmful emissions, particularly unburned methane, a potent greenhouse gas. This innovative practice distinguishes itself from continuous injection because it allows for more precise control of the combustion process with only a slight increase in system complexity. By synchronizing the injection of natural gas with the intake and exhaust valve opening and closing times while also considering the gas path in the manifolds, methane release into the atmosphere is significantly reduced, making a substantial contribution to efforts to address climate change. Moreover, phased injection improves the efficiency of marine engines, resulting in reduced overall fuel consumption, lower fuel costs, and increased ship autonomy. This technology has been tested on a single-cylinder, large-bore, four-stroke research engine designed for marine applications, operating in dual-fuel mode with diesel and natural gas. Performance was compared with that of the conventional continuous feeding method. Evaluation of the effect on equivalent CO2 emissions indicates a potential reduction of up to approximately 20%. This reduction effectively brings greenhouse gas emissions below those of the diesel baseline case, especially when injection control is combined with supercharging control to optimize the air-fuel ratio.