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Abstract Cardiovascular disease remains a leading cause of morbidity and mortality after kidney transplantation (KT). Although statins reduce cardiovascular risk and have renal benefits in the general population, their effects on KT recipients are not well-established. We studied the effects of early statin use (within 1-year post-transplantation) on long-term outcomes in 714 KT recipients from the Korean cohort study for outcome in patients with KT. Compared with the control group, statin group recipients were significantly older, had a higher body mass index, and had a higher prevalence of diabetes mellitus. During a median follow-up of 85 months, 74 graft losses occurred (54 death-censored graft losses and 20 deaths). Early statin use was independently associated with lower mortality (hazard ratio, 0.280; 95% confidence interval 0.111–0.703) and lower death-censored graft loss (hazard ratio, 0.350; 95% confidence interval 0.198–0.616). Statin therapy significantly reduced low-density lipoprotein cholesterol levels but did not decrease the risk of major adverse cardiovascular events. Biopsy-proven rejection and graft renal function were not significantly different between statin and control groups. Our findings suggest that early statin use is an effective strategy for reducing low-density lipoprotein cholesterol and improving patient and graft survival after KT.

Posttransplant lymphoproliferative disorders (PTLDs) are severe complications with heterogeneous clinical pictures involving abnormal lymphoproliferation in solid organ transplants and are known to be closely associated with Epstein-Barr virus (EBV) infection. Herein, we present a case of graft lymphoma in a febrile kidney transplant recipient. A 37-year-old woman was admitted with an abrupt 39 °C fever, mild graft discomfort, and gross hematuria. She had received deceased donor kidney transplantation 8 years earlier, but developed graft failure due to a recurrence of immunoglobulin A nephropathy. Laboratory tests revealed anemia and elevated levels of inflammatory markers. Enhanced abdominopelvic computed tomography showed graft swelling with perirenal fat stranding. Thus, we administered antibiotics for a urinary tract infection and increased the doses of steroids due to suspicion of graft intolerance syndrome. However, the patient's symptoms gradually worsened. Eventually, we performed graft nephrectomy and histologically confirmed EBV-positive diffuse large B cell lymphoma. We report a case in which a PTLD was considered in the differential diagnosis of a kidney transplant recipient with symptoms similar to those of a urinary tract infection or graft intolerance syndrome.

IntroductionKlebsiella pneumoniae can cause a wide range of infections. Hypervirulent K. pneumoniae (hvKp), particularly associated with the K1 and K2 capsular types, is an increasingly significant microorganism with the potential to cause invasive infections, including renal abscesses. Despite the rising prevalence of hvKp infections, information on renal abscesses caused by K. pneumoniae is limited, and the clinical significance of hvKp associated with specific virulence genes remains elusive.MethodsThis study performed at a 1200-bed tertiary hospital sought to identify the clinical and microbiological characteristics of renal abscesses caused by K. pneumoniae, focusing on various virulence genes, including capsular serotypes and multilocus sequence typing (MLST).ResultsOver an 8-year period, 64 patients with suspected renal abscesses were reviewed. Ten patients diagnosed with K. pneumoniae-related renal abscesses were ultimately enrolled in the study. Among the isolates from the 10 patients, capsular serotype K2 was predominant (40.0%), followed by K1 (30.0%). The most common sequence type by MLST was 23 (40.0%). In particular, six patients (60.0%) harbored specific genes indicative of hvKp: iucA, peg-344, rmpA, and rmpA2.ConclusionsOur findings highlight the importance of hvKp as a pathogen in renal abscesses. Although the nature of hvKp is relatively unknown, it is widely recognized as a highly virulent pathogen that can infect relatively healthy individuals of various ages and simultaneously cause infections at multiple anatomical sites. Therefore, when treating patients with K. pneumoniae-related renal abscesses, caution is necessary when considering the characteristics of hvKp, such as potential bacteremia, multi-organ abscess formation, and metastatic spread.

The present paper aims to investigate some semi-separation axioms relating to the Alexandroff one point compactification (Alexandroff compactification, for short) of the digital plane with the Marcus-Wyse ($ MW $-, for brevity) topology. The Alexandroff compactification of the $ MW $-topological plane is called the infinite $ MW $-topological sphere up to homeomorphism. We first prove that under the $ MW $-topology on $ {\mathbb Z}^2 $ the connectedness of $ X(\subset {\mathbb Z}^2) $ with $ X^\sharp\geq 2 $ implies the semi-openness of $ X $. Besides, for the infinite $ MW $-topological sphere, we introduce a new condition for the hereditary property of the compactness of it. In addition, we investigate some conditions preserving the semi-openness or semi-closedness of a subset of the $ MW $-topological plane in the process of an Alexandroff compactification. Finally, we prove that the infinite $ MW $-topological sphere is a semi-regular space; thus, it is a semi-$ T_3 $-space because it is a semi-$ T_1 $-space. Hence we finally conclude that an Alexandroff compactification of the $ MW $-topological plane preserves the semi-$ T_3 $ separation axiom.

Abstract Background The coinfection between cytomegalovirus (CMV) and either human herpesvirus‐6 (HHV‐6) or HHV-7 in renal transplant recipients is well known; however, there have been few reports of coinfection of CMV associated with HHV-8. This paper presents a first case of acute gastric ulcer and duodenitis associated with CMV and HHV‐8 coinfection after renal transplantation. Case presentation A 33-year-old male with a history of kidney transplantation was admitted to hospital because of postural epigastric pain. The recipient was CMV seropositive prior to transplantation and received trimethoprim-sulfamethoxazole without universal prophylaxis. Approximately 5 months after renal transplant, the recipient complained postural epigastric pain. An endoscopy revealed diffuse ulcerative lesions in the lower body and in the antrum of the stomach, as well as several erythematous mucosal lesions in the duodenum. Histopathologic examination identified CMV inclusions consistent with invasive CMV disease and immunohistochemical staining showed positive results for HHV-8 and CMV. No tumorous diseases such as Kaposi’s sarcoma were detected. After 3 weeks of intravenous ganciclovir treatment, we observed that serum CMV PCR remained within the normal range and clinical symptoms improved. A follow-up endoscopy performed 3 weeks later showed that the severity of the above mentioned lesions had improved. Conclusions We report the first case of a renal transplant recipient diagnosed with acute gastric ulcer and duodenitis associated with coinfection of CMV and HHV-8. Ganciclovir appears to be effective in diseases associated with coinfection of CMV and HHV-8.

Background/Aims Renal recovery of a kidney donor after undergoing nephrectomy though challenging is essential. We aimed to examine the effect of estimated glomerular filtration rate (eGFR) percent change at 1-month post-donation on insufficient kidney function after kidney donation. Methods A total of 3,952 living kidney donors who underwent donor nephrectomy from 1982 to 2019 from eight different tertiary hospitals in Korea were initially screened. Percent changes in the eGFR from baseline to 1-month post-donation were calculated. The degree of percent changes was categorized by quartile, and the 1st quartile was regarded as the group with the lowest decreased eGFR at 1-month after donation. The remaining eGFR less than 60 mL/min/1.73 m2 was the end-point. The Cox proportional hazard model was used for evaluating the impact of initial eGFR and eGFR percent change at 1-month post-donation on the condition with remaining eGFR < 60 mL/min/1.73 m2. In the multivariate analysis, we used variables with a p < 0.1 in the univariate analysis. Results A total of 1,585 donors were included in the analysis. During 62.2 ± 49.3 months, 13.7% of donors showed renal insufficiency. The 4th (adjusted hazard ratio [aHR], 10.41; 95% confidence interval [CI], 5.15 to 21.04) and the 3rd (aHR, 4.29; 95% CI, 2.15 to 8.56) quartiles of percent change in eGFR and the pre-donation eGFR (aHR, 0.90; 95% CI, 0.88 to 0.92) were associated with the development of renal insufficiency. Conclusions The impact of worse initial renal recovery on renal insufficiency was pronounced in donors with lower pre-donation eGFRs. Additionally, worse initial renal recovery of remaining kidney affected the long-term development of renal insufficiency in kidney donors.

Background It remains unclear whether immunosuppressive agents are effective in patients with immunoglobulin A nephropathy (IgAN). We investigated the efficacy of a mycophenolate mofetil (MMF) and corticosteroid combination therapy in patients with advanced IgAN. Methods We conducted a multicenter, randomized, placebo-controlled, parallel-group study of 48 weeks administration of MMF and corticosteroids in biopsy-proven advanced IgAN patients with estimated glomerular filtration rate (eGFR) of 20–50 mL/min/1.73 m2 and urine protein-to-creatinine ratio (UPCR) of >0.75 g/day. The primary outcome was complete (UPCR < 0.3 g/day) or partial (>50% reduction of UPCR compared to baseline) remission at 48 weeks. Results Among the 48 randomized patients, the percentage that achieved complete or partial remission was greater in thecombination therapy group than in the control group (4.2% vs. 0% and 29.1% vs. 5.0%, respectively). Compared with the combination therapy group, eGFR in the control group decreased significantly from week 36 onward, resulting in a final adjusted mean change of –4.39 ± 1.22 mL/min/1.73 m2 (p = 0.002). The adjusted mean changes after 48 weeks were 0.62 ± 1.30 and –5.11 ± 1.30 mL/min/1.73 m2 (p = 0.005) in the treatment and control groups, respectively. The UPCR was significantly different between the two groups; the adjusted mean difference was –0.47 ± 0.17 mg/mgCr and 0.07 ± 0.17 mg/mgCr in the treatment and control group, respectively (p = 0.04). Overall adverse events did not differ between the groups. Conclusion In advanced IgAN patients with a high risk for disease progression, combined MMF and corticosteroid therapy appears to be beneficial in reducing proteinuria and preserving renal function.

Abstract Data for Asian kidney transplants are very limited. We investigated the relative importance of prognostic markers in Asian kidney transplants by using Korean Organ Transplantation Registry (KOTRY) cohort. Prediction models were developed by data-driven variable selection approach. The relative importance of the selected predictors was measured by dominance analysis. A total of 4854 kidney transplant donor-recipient pairs were analyzed. Overall patient survival rates were 99.8%, 98.8%, and 91.8% at 1, 3, and 5 years, respectively. Death-censored graft survival rates were 98.4%, 97.0%, and 95.8% at 1, 3, and 5 years. Biopsy-proven acute rejection free survival rates were 90.1%, 87.4%, and 87.03% at 1, 3, and 5 years. The top 3 dominant predictors for recipient mortality within 1 year were recipient cardiovascular disease history, deceased donor, and recipient age. The dominant predictors for death-censored graft loss within 1 year were acute rejection, deceased donor, and desensitization. The dominant predictors to acute rejection within 1 year were donor age, HLA mismatched numbers, and desensitization. We presented clinical characteristics of patients enrolled in KOTRY during the last 5 years and investigated dominant predictors for early post-transplant outcomes, which would be useful for clinical decision-making based on quantitative measures.

Background Long-term outcomes of live kidney donors remain controversial, although this information is crucial for selecting potential donors. Thus, this study compared the long-term risk of all-cause mortality between live kidney donors and healthy control. Methods We performed a retrospective cohort study including donors from seven tertiary hospitals in South Korea. Persons who underwent voluntary health screening were included as controls. We created a matched control group considering age, sex, era, body mass index, baseline hypertension, diabetes, estimated glomerular filtration rate, and dipstick albuminuria. The study outcome was progression to end-stage kidney disease (ESKD), and all-cause mortality as identified in the linked claims database. Results We screened 1,878 kidney donors and 78,115 health screening examinees from 2003 to 2016. After matching, 1,701 persons remained in each group. The median age of the matched study subjects was 44 years, and 46.6% were male. Among the study subjects, 2.7% and 16.6% had underlying diabetes and hypertension, respectively. There were no ESKD events in the matched donor and control groups. There were 24 (1.4%) and 12 mortality cases (0.7%) in the matched donor and control groups, respectively. In the age-sex adjusted model, the risk for all-cause mortality was significantly higher in the donor group than in the control group. However, the significance was not retained after socioeconomic status was included as a covariate (adjusted hazard ratio, 1.82; 95% confidence interval, 0.87–3.80). Conclusion All-cause mortality was similar in live kidney donors and matched non-donor healthy controls with similar health status and socioeconomic status in the Korean population.

The present paper intensively studies various properties of certain topologies on the set of integers $ {\mathbb Z} $ (resp. $ {\mathbb Z}^n $) which are either homeomorphic or not homeomorphic to the typical Khalimsky line topology (resp. $ n $-dimensional Khalimsky topology). This finding plays a crucial role in addressing some problems which remain open in the field of digital topology.

Background Considering the growing prevalence of Western lifestyles and related chronic diseases occurring in South Korea, this study aimed to explore the progression of metabolic risk factors in living kidney donors. Methods This study enrolled living kidney donors from seven hospitals from 1982 to 2016. The controls were individuals that voluntarily received health check-ups from 1995 to 2016 that were matched with donors according to age, sex, diabetes status, baseline estimated glomerular filtration rate, and date of the medical record. Data on hyperuricemia, hypertension, hypercholesterolemia, and overweight/obesity were collected to determine metabolic risks. Logistic regressions with interaction terms between the medical record date and donor status were used to compare the trends in metabolic risks over time in the two groups. Results A total of 2,018 living kidney donors and matched non-donors were included. The median age was 44.0 years and 54.0% were women. The living kidney donors showed a lower absolute prevalence for all metabolic risk factors, except for those that were overweight/obese, than the non-donors. The proportion of subjects that were overweight/obese was consistently higher over time in the donor group. The changes over time in the prevalence of each metabolic risk were not significantly different between groups, except for a lower prevalence of metabolic risk factors ≥ 3 in donors. Conclusion Over time, metabolic risks in living kidney donors are generally the same as in non-donors, except for a lower prevalence of metabolic risk factors ≥3 in donors.

Given two digital images $ (X_i, k_i), i \in \{1, 2\} $, first of all we establish a new $ PN_k $-adjacency relation in a digital product $ X_1 \times X_2 $ to obtain a relation set $ (X_1 \times X_2, PN_k) $, where the term $ ''$$ PN $" means $ ''$pseudo-normal". Indeed, a $ PN $-$ k $-adjacency is softer or broader than a normal $ k $-adjacency. Next, the present paper initially develops both $ PN $-$ k $-continuity and $ PN $-$ k $-isomorphism. Furthermore, it proves that these new concepts, the $ PN $-$ k $-continuity and $ PN $-$ k $-isomorphism, need not be equal to the typical $ k $-continuity and a $ k $-isomorphism, respectively. Precisely, we prove that none of the typical $ k $-continuity (resp. typical $ k $-isomorphism) and the $ PN $-$ k $-continuity (resp. $ PN $-$ k $-isomorphism) implies the other. Then we prove that for each $ i \in \{1, 2\} $, the typical projection map $ P_i: X_1 \times X_2 \to X_i $ preserves a $ PN_k $-adjacency relation in $ X_1 \times X_2 $ to the $ k_i $-adjacency relation in $ (X_i, k_i) $. In particular, using a $ PN $-$ k $-isomorphism, we can classify digital products with $ PN_k $-adjacencies. Furthermore, in the category of digital products with $ PN_k $-adjacencies and $ PN $-$ k $-continuous maps between two digital products with $ PN_k $-adjacencies, denoted by $ DTC_k^\blacktriangle $, we finally study the (almost) fixed point property of $ (X_1 \times X_2, PN_k) $.

Common neuropsychiatric complications of tacrolimus include tremors, fatigue, headache, sleep disorders, paranoid reactions, and anxiety. Other, more serious complications include encephalopathy, convulsions, confusion, and coma. To our knowledge, however, severe weight loss by anorexia has not been reported as a neuropsychiatric adverse effect of tacrolimus given to adult kidney transplant recipients. In this article we present two cases of severe anorexia and weight loss associated with tacrolimus that appeared to reverse with cyclosporine.

Abstract Recently, waist to hip ratio (WHR) has been reported to be a better indicator of predicting cardiovascular outcomes than body mass index (BMI). We evaluated the effects of pre or post-transplant changes of WHR or BMI on the new onset cardiovascular diseases (CVD) in recipients of kidney transplantation (KT). A total of 572 patients were enrolled from a multicenter observational cohort (KNOW-KT). Measurement of WHR and BMI was done at pre-KT, first and last visit year after KT, and the changes of these parameters and their effect on the incident CVD were analyzed. During the median follow up period of 32.73 ± 15.26 months, the new onset CVD developed in 31 out of 572 patients. The older age, diabetes mellitus and increase of WHR from pre KT or previous follow up year were found to be independent factors predicting the new onset CVD in these patients. However, baseline BMI, WHR prior to KT did not predict the incident CVD. The new metabolic burden, presented as increase of WHR in KT patients has a critical impact on the development of new onset CVD. Strategies to prevent the metabolic burden after KT might improve cardiovascular outcomes and patient’s survival.

With the increasing demand for organ transplantation, organ procurement from a deceased donor is an essential step for deceased donor organ transplantation. A proper surgical technique for the procurement of an organ graft from a deceased donor must be carried out to avoid any damage to it. Moreover, how to manage deceased donors until they enter the operating room in a stable condition is a critical point to be considered. The establishment of a surgical technique and preoperative management for organ procurement is encouraged to achieve a nationwide standard and consistency for organ graft sharing among the transplant units.

Human immunodeficiency virus (HIV) infection was traditionally considered an absolute contraindication for transplantation because of concerns about HIV disease progression due to immunosuppression. Since potent antiretroviral therapies (ARTs) have become widely available, the prognosis of HIV-infected kidney transplant recipients has dramatically improved. Recent results of prospective multicenter trials on kidney transplantation (KT) in HIV-positive candidates have demonstrated the success and challenges of transplantation in this population. Several studies have reported comparable patient and graft outcomes between HIV-infected and HIV-uninfected recipients after KT in the era of potent combined ARTs. We report two cases of HIV-infected patients who underwent KT at our hospital. In this paper, we present a detailed report of two cases and provide a short review of the existing literature.

Renal functional deterioration is associated with physical and mental burdens for kidney transplant (KT) and chronic kidney disease (CKD) patients. However, the change in health-related quality of life (HRQOL) over time in KT patients compared to that of native CKD patients has not been evaluated. We addressed this issue using KT patients registered in the KNOW-KT cohort study and patients at CKD stage 1-3 registered in the KNOW-CKD cohort study. HRQOL scores were assessed using the Kidney Disease Quality of Life Short Form at baseline, 2-, and 4-years follow-up in 842 KT patients and at baseline and 5-year follow-up in 1,355 CKD patients. SF-36 scores declined at the 4-year follow-up, whereas CKD-targeted scores showed no change in the KT group. In contrast, CKD-targeted scores as well as SF-36 scores were decreased at the 5-year follow-up in CKD patients. When prognostic factors were analyzed for longitudinal HRQOL data over time, renal functions, diabetes, cardiovascular and cerebrovascular diseases, hemoglobin level, marital status, income, employment, and health care were significant prognostic factors. Furthermore, KT was an independent prognostic factor for better HRQOL. These results highlight that KT can offer a better HRQOL than that of CKD patients, even when renal function is similar.

BackgroundLittle is known regarding optimal tacrolimus (TAC) trough levels after 1 year post-transplant in stable kidney transplant recipients (KTRs) who have not experienced renal or cardiovascular outcomes. This study aimed to investigate the effect of 1-year post-transplant TAC trough levels on long-term renal and cardiovascular outcomes and opportunistic infections in stable KTRs.MethodsKTRs receiving TAC with mycophenolate-based immunosuppression who did not experience renal or cardiovascular outcomes within 1 year post-transplant were enrolled from a multicenter observational cohort study. Renal outcome was defined as a composite of biopsy-proven acute rejection, interstitial fibrosis and tubular atrophy, and death-censored graft loss. Cardiovascular outcome was defined as a composite of de novo cardiomegaly, left ventricular hypertrophy, and cardiovascular events. Opportunistic infections were defined as the occurrence of BK virus or cytomegalovirus infections.ResultsA total of 603 eligible KTRs were divided into the low-level TAC (LL-TAC) and high-level TAC (HL-TAC) groups based on a median TAC level of 5.9 ng/mL (range 1.3-14.3) at 1 year post-transplant. The HL-TAC group had significantly higher TAC trough levels at 2, 3, 4, and 5 years compared with the levels of the LL-TAC group. During the mean follow-up of 63.7 ± 13.0 months, there were 121 renal outcomes and 224 cardiovascular outcomes. In multivariate Cox regression analysis, LL-TAC and HL-TAC were not independent risk factors for renal and cardiovascular outcomes, respectively. No significant differences in the development of opportunistic infections and de novo donor-specific anti-human leukocyte antigen antibodies and renal allograft function were observed between the two groups.ConclusionsTAC trough levels after 1 year post-transplant remained at a similar level until the fifth year after kidney transplantation and were not directly associated with long-term outcomes in stable Korean KTRs who did not experience renal or cardiovascular outcomes. Therefore, in Asian KTRs with a stable clinical course, TAC trough levels higher than approximately 6 ng/mL might not be required after a year of kidney transplantation.

Objective. This study used a continuous glucose monitoring system (CGMS) to investigate the glucose profiles and assess the degree of hyperglycemic excursion after kidney or liver transplantation during the early period after operation. Methods. Patients to whom a CGMS was attached during a postoperative period of approximately one month after transplantation were included. The CGM data of 31 patients including 24 with kidney transplantation (KT) and seven with liver transplantation (LT) were analyzed. Results. Hyperglycemia over 126 mg/dL (fasting) or 200 g/dL (postprandial) occurred in 42.1% (8/19) and 16.7% (1/6) of KT and LT patients, respectively, during this early period after transplantation, except for patients with preexisting diabetes (5 KT, 1 LT). The average mean amplitude of glycemic excursion (MAGE) and mean absolute glucose (MAG) levels were 91.18±26.51 vs. 65.66±22.55 (P

The increase in greenhouse gas (GHG) emissions has resulted in climate change and global warming. Human activities in many sectors, including agriculture, contribute to approximately 9.2% of total GHG emissions from Annex I countries. An argument on issues of livestock being the highest contributor to GHG emissions has grown since FAO’s 2006 report Livestock’s Long Shadow. The issue has continued growing, conflicting the importance of the industry in terms of food security and livelihoods, thus, monitoring GHG emission from this sector is vital. The most commonly used methods for calculating GHG emissions from the livestock sector are life cycle assessment (LCA) and the GHG inventory. Although the LCA presents information on the impacts of the livestock industry on the environment, the GHG inventory is the main tool used internationally for GHG reporting. This review comprehensively discusses the source of GHG emissions from the livestock industry and its estimation methodology, as well as the current strategies for mitigating these emissions.

Abstract Van der Waals (vdW) magnetic materials are comprised of layers of atomically thin sheets, making them ideal platforms for studying magnetism at the two-dimensional (2D) limit. These materials are at the center of a host of novel types of experiments, however, there are notably few pathways to directly probe their magnetic structure. We confirm the magnetic order within a single crystal of NiPS3 and show it can be accessed with resonant elastic X-ray diffraction along the edge of the vdW planes in a carefully grown crystal by detecting structurally forbidden resonant magnetic X-ray scattering. We find the magnetic order parameter has a critical exponent of β ~ 0.36, indicating that the magnetism of these vdW crystals is more adequately characterized by the three-dimensional (3D) Heisenberg universality class. We verify these findings with first-principles density functional theory, Monte-Carlo simulations, and density matrix renormalization group calculations.

Unlike the study of the fixed point property (FPP, for brevity) of retractable topological spaces, the research of the FPP of non-retractable topological spaces remains. The present paper deals with the issue. Based on order-theoretic foundations and fixed point theory for Khalimsky (K-, for short) topological spaces, the present paper studies the product property of the FPP for K-topological spaces. Furthermore, the paper investigates the FPP of various types of connected K-topological spaces such as non-K-retractable spaces and some points deleted K-topological (finite) planes, and so on. To be specific, after proving that not every one point deleted subspace of a finite K-topological plane X is a K-retract of X, we study the FPP of a non-retractable topological space Y, such as one point deleted space Y ∖ { p } .

Background: Interstitial tonicity increases vascular endothelial growth factor-C (VEGF-C), a lymphangiogenic factor in salt-induced hypertension. Therefore, it can be assumed that changes of serum VEGF-C level may be associated with increasing blood pressure. However, there is no report about the changes of serum VEGF-C levels in patients with chronic kidney disease (CKD). The aims of this study were to investigate the changes of serum and urine VEGF-C levels in patients with CKD stage 3–4 and to evaluate the relationship between blood pressure and serum VEGF-C levels in the patients with CKD stage 5 and hemodialysis. Methods: Glomerular filtration rate (GFR) was assessed by the Modification of Diet in Renal Disease equation. Blood pressure and VEGF-C levels (serum and urine) were measured by enzyme-linked immunosorbent assay (ELISA) in nine patients with stage 3–4 CKD, 41 hemodialysis patients, and eight healthy individuals. Results: The median serum level of VEGF-C in patients with stage 3–4 CKD and stage 5 hemodialysis significantly decreased in comparison with healthy individuals. Urinary VEGF-C excretion increased in patients with stage 3–4 CKD compared with healthy control patients. For 41 hemodialysis patients, the serum level of VEGF-C in patients with stage 1 or stage 2 hypertension with hemodialysis did not significantly increase when compared with prehypertension hemodialysis patients. Conclusion: We demonstrated that circulating levels of VEGF-C were decreased in patients with CKD, and the decrease of VEGF-C in patients with stage 3–4 CKD coincided with an increase in the urinary excretion of VEGF-C.

A critical step in the manufacturing of oligonucleotides is the selection of ideal solid supports. Herein, we evaluate a hybrid core–shell solid support made of polystyrene and polyethyleneglycol, for the preparation of oligonucleotides using phosphoramidite chemistry. The results were compared with those obtained using conventional solid supports including controlled-pore glass and polystyrene NittoPhase®. The core–shell supports provided good yields when phosphoramidites were dissolved in dichloromethane. Automatic DNA synthesizer was used to prepare several oligonucleotides carrying natural phosphate, phosphorothioate linkages, lipid conjugates and mesyl phosphoramidate dimers in acceptable yields. This study represents the first reported use of core–shell particles for the synthesis of chemically modified oligonucleotide sequences of therapeutic significance.

Hypertensive nephrosclerosis is usually associated with chronic hypertension, which increases the risk of progressive renal disease. Among the causes of malignant hypertension, thrombotic microangiopathy is complicated and is associated with renal dysfunction at the time of diagnosis. In this case, a young man with hypertension presented with renal failure and thrombocytopenia in the emergency department. This case emphasizes the importance of early recognition of renal failure and thrombocytopenia among patients with uncontrolled hypertension.

Hemorrhagic fever with renal syndrome (HFRS) is an acute viral disease with fever, hemorrhage and renal failure caused by hantavirus infection. Hantavirus induces HFRS or hantavirus pulmonary syndrome (HPS). HPS progression to a life-threatening pulmonary disease is found primarily in the USA and very rarely in South Korea. Here, we report a case of HFRS and coexisting HPS.

Breathing is the process of exchanging gases between the human body and the surrounding environment. It plays a vital role in maintaining human health, sustaining life, and supporting various bodily functions. Unfortunately, current methods for monitoring respiration are impractical for medical applications because of their high costs and need for bulky equipment. When measuring changes in moisture during respiration, we observed a slow response time for 2D nanomaterial-based resistance measurement methods used in respiration sensors. Through thermal annealing, the crystal structure of MoS2 is transformed from 1T@2H to 2H, allowing the measurement of respiration at more than 30 cycles per minute and enabling analysis of the response. This study highlights the potential of two-dimensional nanomaterials for the development of low-cost and highly sensitive humidity and respiration sensors for various applications.

Abstract Acanthopanax senticosus belongs to Araliaceae family and is traditionally used as a tonic. The roots and stems are mainly used as treatments for hypodynamia, rheumatism, and hypertension, but their frequent use may lead to extinction. However, comprehensive and simultaneous analysis of the remaining parts were still limited. There is a need to reorganize them for standardization of functional foods. In this study, 50 phenolic compounds and 82 triterpenoid saponins from the shoots, leaves, fruits, and stems of were characterized using UPLC-QTOF-MS and UPLC-QTRAP-MS/MS. Among them, 52 compounds were newly determined as the cis and malonyl-bound phenolic acids and were found to be structural isomers of Acanthopanax flavonoids and saponins. All compounds were absolutely/relatively quantified, and shoots had the highest content. Peroxynitrite and α-glucosidase inhibitory activities were performed, followed by evaluation of structure-activity relationships. Particularly, hederasaponin B and ciwujianoside B showed remarkable efficacy, which were affected by the C-23 hydroxylation, the C-20(29) double bond, and the presence of rhamnose. These detailed profiling can be used as fundamental data for increasing the utilization of A. senticosus and developing them into functional foods.

Abstract Background Ionizing radiation has been used for mutagenesis or material modification. The potential to use microalgae as a platform for antimicrobial production has been reported, but little work has been done to advance it beyond characterization to biotechnology. This study explored two different applications of ionizing radiation as a metabolic remodeler and a molecular modifier to enhance the antimicrobial activity of total protein and solvent extracts of Chlamydomonas reinhardtii cells. Results First, highly efficient transgenic C. reinhardtii strains expressing the plant-derived antimicrobial peptides, AtPR1 or AtTHI2.1, were developed using the radiation-inducible promoter, CrRPA70Ap. Low transgene expression was significantly improved through X-irradiation (12–50 Gy), with peak activity observed within 2 h. Protein extracts from these strains after X-irradiation showed enhanced antimicrobial activity against the prokaryotic bacterium, Pseudomonas syringae, and the eukaryotic fungus, Cryptococcus neoformans. In addition, X-irradiation (12 Gy) increased the growth and biomass of the transgenic strains. Second, C. reinhardtii cell extracts in ethanol were γ-irradiated (5–20 kGy), leading to molecular modifications and increased antimicrobial activity against the phytopathogenic bacteria, P. syringae and Burkholderia glumae, in a dose-dependent manner. These changes were associated with alterations in fatty acid composition. When both transgenic expression of antimicrobial peptides and molecular modification of bioactive substances were applied, the antimicrobial activity of C. reinhardtii cell extracts was further enhanced to some extent. Conclusion Overall, these findings suggest that ionizing radiation can significantly enhance the antimicrobial potential of C. reinhardtii through efficient transgene expression and molecular modification of bioactive substances, making it a valuable source of natural antimicrobial agents. Ionizing radiation can act not only as a metabolic remodeler of transgene expression in microalgae but also as a molecular modifier of the bioactive substances.

Abstract Purpose Measurement of corneal endothelial cells is critical for postoperative evaluation of phakic intraocular lens (pIOL) surgery. However, inter-instrument differences in corneal endothelial cell density (ECD) after pIOL implantation have not yet been reported. This study aimed to compare automated corneal endothelial cell analysis between CellChek-20 (Konan Medical, Hyogo, Japan) and EM-4000 (Tomey, Nagoya, Japan) in healthy and postoperative eyes with pIOL. Methods We retrospectively analyzed 154 healthy and 236 postoperative eyes after pIOL surgery. Endothelial cell measurements were performed using CellChek-20 and EM-4000 with autofocusing and automated image analysis. ECD, percentage of hexagonal cells (HEX), coefficient of variation in cell size (CoV), and central corneal thickness (CCT) were compared between the two devices. Results The ECDs of the two devices were highly correlated in both healthy (Spearman’s correlation coefficient [r] = 0.805; p

Background/Aims Atezolizumab plus bevacizumab (ATE+BEV) therapy has become the recommended first-line therapy for patients with unresectable hepatocellular carcinoma (HCC) because of favorable treatment responses. However, there is a lack of data on sequential regimens after ATE+BEV treatment failure. We aimed to investigate the clinical outcomes of patients with advanced HCC who received subsequent systemic therapy for disease progression after ATE+BEV. Methods This multicenter, retrospective study included patients who started second-line systemic treatment with sorafenib or lenvatinib after HCC progressed on ATE+BEV between August 2019 and December 2022. Treatment response was assessed using the Response Evaluation Criteria in Solid Tumors (version 1.1.). Clinical features of the two groups were balanced through propensity score (PS) matching. Results This study enrolled 126 patients, 40 (31.7%) in the lenvatinib group, and 86 (68.3%) in the sorafenib group. The median age was 63 years, and males were predominant (88.1%). In PS-matched cohorts (36 patients in each group), the objective response rate was similar between the lenvatinib- and sorafenib-treated groups (5.6% vs. 8.3%; P=0.643), but the disease control rate was superior in the lenvatinib group (66.7% vs. 22.2%; P

Objective Methylenetetrahydrofolatereductase (MTHFR) is important for folate metabolism, which is involved in DNA synthesis and cell growth. However, the relationship between Maternal MTHFR polymorphisms and outcomes in assisted reproduction remains controversial. This is the first study to explore the effect of MTHFR polymorphisms on the embryological outcomes in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles in Korean patients with infertility.Materials and methods This retrospective cohort study included 173 women who underwent MTHFR genotyping between July, 2021 and June, 2022. The embryologic outcomes of 301 IVF/ICSI cycles were compared between groups according to MTHFR polymorphisms using ANOVA and Chi-square test.Results Oocyte maturation rates were 80.0%, 75.0%, and 71.4% for MTHFR 677CC, 677CT, and 677TT, respectively. Cleaved embryo formation and transplantable embryo rates were comparable across various maternal MTHFR 677 genotypes. Good-quality embryo (GQE) rate was higher for MTHFR 677CT than those for 677CC and 677TT (40.0% vs. 29.4%, p = 0.001 and 40.0% vs. 33.3%, p = 0.025, respectively). When analyzing the combined MTHFR genotypes, the oocyte maturation rate was significantly lower in 677TT than in 677CC 1298AA/677CC 1298AC and 677CC 1298CC/677CT 1298AA/677CT 1298AC (71.4% vs. 76.7%, p = 0.012 and 71.4% vs. 75.7%, p = 0.029, respectively). The MTHFR 677CC/1298CC, 677CT/1298AA, and 677CT/1298AC genotypes had the highest GQE rates.Conclusions MTHFR 677TT genotype, which had the lowest enzymatic activity, had the lowest oocyte maturation rate. The combined MTHFR 677CC/1298CC, 677CT/1298AA, and 677CT/1298AC genotypes with intermediate enzyme activities had higher GQE rates. However, no differences were observed in the transplantable embryo rate between MTHFR genotypes.

Study region: The Seohwa watershed, South Korea. Study focus: Agricultural practices and urbanization in watersheds increase nutrient loads (total nitrogen (TN), total phosphorus (TP), and nitrate-nitrogen (NO3--N)) in streams and deteriorate water quality. Between October 2017 and October 2018, water samples were collected from a small stream (MS), main tributary (TS), and sub-tributaries (ST) characterized by different land-use patterns. The objective of this study was to identify the sources that determine water quality in the respective streams and to estimate whether water quality was dependent on land-use patterns. New hydrological insights for the region: TN in MS progressively decreased downstream, whereas such spatial variation was not observed in TS and ST. For TP, TS and ST samples showed elevated concentrations during storm events, but not in MS. These observations resulted from TN and TP derived from natural and anthropogenic sources associated with land-use patterns. Interestingly, TN/TP ratios were strongly negatively correlated with the proportion of residential area (R2 = 0.92) rather than other land-use patterns such as agricultural area and forest. In addition, statistical analysis and dual isotopes of nitrate (NO3-) showed that the water quality in MS and the one in TS and ST were predominantly affected by natural sources and anthropogenic sources, respectively. Considering the effects of land-use patterns and rainfall on water quality, anthropogenic sources should be precisely identified to manage stream water in small watersheds more effectively.

Abstract Generating 3D bone cell networks in vitro that mimic the dynamic process during early bone formation remains challenging. Here, we report a synthetic biodegradable microporous hydrogel for efficient formation of 3D networks from human primary cells, analysis of cell-secreted extracellular matrix (ECM) and microfluidic integration. Using polymerization-induced phase separation, we demonstrate dynamic in situ formation of microporosity (5–20 µm) within matrix metalloproteinase-degradable polyethylene glycol hydrogels in the presence of living cells. Pore formation is triggered by thiol-Michael-addition crosslinking of a viscous precursor solution supplemented with hyaluronic acid and dextran. The resulting microporous architecture can be fine-tuned by adjusting the concentration and molecular weight of dextran. After encapsulation in microporous hydrogels, human mesenchymal stromal cells and osteoblasts spread rapidly and form 3D networks within 24 hours. We demonstrate that matrix degradability controls cell-matrix remodeling, osteogenic differentiation, and deposition of ECM proteins such as collagen. Finally, we report microfluidic integration and proof-of-concept osteogenic differentiation of 3D cell networks under perfusion on chip. Altogether, this work introduces a synthetic microporous hydrogel to efficiently differentiate 3D human bone cell networks, facilitating future in vitro studies on early bone development.

The leafhopper genus Parabolopona of Korea is reviewed. Two species of the genus are reported from Korea: Parabolopona ishihari Webb, 1981, and Parabolopona cygnea Cai & Shen, 1999. We provide morphological information on the species, a key to the Korean Parabolopona species, and a checklist of the world.

Abstract The biogeographical range shift of insect pests is primarily governed by temperature. However, the range shift of seasonal long-distance migratory insects may be very different from that of sedentary insects. Nilaparvata lugens (BPH), a serious rice pest, can only overwinter in tropical-to-subtropical regions, and some populations migrate seasonally to temperate zones with the aid of low-level jet stream air currents. This study utilized the CLIMEX model to project the overwintering area under the climate change scenarios of RCP2.6 and RCP8.5, both in 2030s and 2080s. The overwintering boundary is predicted to expand poleward and new overwintering areas are predicted in the mid-latitude regions of central-to-eastern China and mid-to-southern Australia. With climate change, the habitable areas remained similar, but suitability decreased substantially, especially in the near-equatorial regions, owing to increasing heat stress. The range shift is similar between RCP2.6-2030s, RCP2.6-2080s, and RCP8.5-2030s, but extreme changes are projected under RCP8.5-2080s with marginal areas increasing from 27.2 to 38.8% and very favorable areas dropping from 27.5 to 3.6% compared to the current climate. These findings indicate that climate change will drive range shifts in BPH and alter regional risks differently. Therefore, international monitoring programs are needed to effectively manage these emerging challenges.

Abstract VISUMAX 800 was introduced to improve the patient experience and clinical outcomes of small incision lenticule extraction (SMILE). This was a retrospective, matched, and case–control study (1:2) controlled for preoperative central corneal thickness and refractive error that compared early refractive and visual outcomes after SMILE using VISUMAX 800 and VISUMAX 500 to treat myopia. We included 50 eyes that underwent the VISUMAX 800 SMILE and 100 eyes that underwent the VISUMAX 500 SMILE. SMILE using VISUMAX 800 was performed using the CentraLign aid for vertex centration. Cyclotorsion was controlled by an OcuLign assistant in the VISUMAX 800 group after corneal marking. Corneal higher-order aberrations (HOAs) were evaluated using a Pentacam 1 month after surgery. No differences were observed in the pre- and post-operative refractive and visual outcomes at 1 day, 1 month, and 6 months after surgery. VISUMAX 800 induced less total HOAs than VISUMAX 500 (P = 0.036). No statistically significant differences were observed in the amounts of induced spherical aberrations or vertical and horizontal comas. No differences were observed in the 1 month and 6 months refractive and visual outcomes between two SMILE procedures, except for VISUMAX 800, which resulted in lower postoperative total HOAs than VISUMAX 500.

Background/Aims Optimal risk stratification based on simplified geriatric assessment to predict treatment-related toxicity and survival needs to be clarified in older patients with diffuse large B-cell lymphoma (DLBCL). Methods This multicenter prospective cohort study enrolled newly diagnosed patients with DLBCL (≥ 65 yr) between September 2015 and April 2018. A simplified geriatric assessment was performed at baseline using Activities of Daily Living (ADL), Instrumental ADL (IADL), and Charlson’s Comorbidity Index (CCI). The primary endpoint was event-free survival (EFS). Results The study included 249 patients, the median age was 74 years (range, 65–88), and 125 (50.2%) were female. In multivariable Cox analysis, ADL, IADL, CCI, and age were independent factors for EFS; an integrated geriatric score was derived and the patients stratified into three geriatric categories: fit (n = 162, 65.1%), intermediate-fit (n = 25, 10.0%), and frail (n = 62, 24.9%). The established geriatric model was significantly associated with EFS (fit vs. intermediate-fit, HR 2.61, p < 0.001; fit vs. frail, HR 4.61, p < 0.001) and outperformed each covariate alone or in combination. In 87 intermediate-fit or frail patients, the relative doxorubicin dose intensity (RDDI) ≥ 62.4% was significantly associated with worse EFS (HR, 2.15, 95% CI 1.30–3.53, p = 0.002). It was related with a higher incidence of grade ≥ 3 symptomatic non-hematologic toxicities (63.2% vs. 27.8%, p < 0.001) and earlier treatment discontinuation (34.5% vs. 8.0%, p < 0.001) in patients with RDDI ≥ 62.4% than in those with RDDI < 62.4%. Conclusions This model integrating simplified geriatric assessment can risk-stratify older patients with DLBCL and identify those who are highly vulnerable to standard dose-intensity chemoimmunotherapy.

Background/Aims: Tegoprazan is a novel potassium-competitive acid blocker that has beneficial effects on acid-related disorders such as gastroesophageal reflux and peptic ulcer diseases. This study aimed to validate the effect of tegoprazan on endoscopic submucosal dissection (ESD)-induced artificial ulcers. Methods : Patients from 16 centers in Korea who underwent ESD for gastric neoplasia were enrolled. After ESD, pantoprazole was administered intravenously for 48 hours. The patients were randomly allocated to either the tegoprazan or esomeprazole group. Tegoprazan 50 mg or esomeprazole 40 mg were administered for 4 weeks, after which gastroscopic evaluation was performed. If the artificial ulcer had not healed, the same dose of tegoprazan or esomeprazole was administered for an additional 4 weeks, and a gastroscopic evaluation was performed. Results : One hundred sixty patients were enrolled in this study. The healing rates of artificial ulcers at 4 weeks were 30.3% (23/76) and 22.1% (15/68) in the tegoprazan and esomeprazole groups, respectively (p=0.006). At 8 weeks after ESD, the cumulative ulcer healing rates were 73.7% (56/76) and 77.9% (53/68) in the tegoprazan and esomeprazole groups, respectively (p=0.210). Delayed bleeding occurred in two patients in the tegoprazan group (2.6%) and in one patient in the esomeprazole group (1.5%). Other adverse events were negligible in both groups. Conclusion : s: Tegoprazan showed similar effects on post-ESD artificial ulcer healing in comparison with esomeprazole.

Abstract Iatrogenic stomach perforation is a detrimental, irreversible, and fatal condition. Traditional surgery and endoscopic suturing clips and devices have been introduced to seal holes and prevent sepsis and disease progression. However, the development of endoscopic devices for perforations remains challenging, with no standard device available. This study investigates the superficial layer approximation strengths of the newly designed ENDOCRAB system for gastric wall defects. Thirty porcine stomachs were prepared ex vivo for the perforation model and distributed equally into three groups: ENDOCRAB system, Through-the-Scope Clip (TTSC), and hand suturing (HS). Both ENDOCRAB and TTSC achieved mucosal–submucosal layer apposition, whereas HS allowed a full-thickness layer. Their air leakage pressure and procedural duration were measured. The analysis of air-leakage pressure demonstrated comparable suture strength between ENDOCRAB (118.5 ± 41.7 mmHg) and HS (127.4 ± 30.2 mmHg, P = 0.812), but inferior strength with TTSC (73.6 ± 21.6 mmHg, P = 0.012). HS achieved the shortest procedural duration, whereas ENDOCRAB and TTSC showed no significant differences. The ENDOCRAB system showed significantly greater strength than the TTSC, was comparable to HS in strength, and required a procedural duration similar to that of the TTSC. Furthermore, long-term in vivo experiments and histological evaluations are essential.

Abstract Potential synergism between Bruton’s tyrosine kinase (BTK) inhibitor and lenalidomide in treating aggressive B-cell lymphoma has been suggested. Here, the authors report a single-arm phase II clinical trial of combination of acalabrutinib, lenalidomide and rituximab (R2A) in patients with aggressive relapsed/refractory aggressive (R/R) B-cell non-Hodgkin lymphoma (NHL). The primary endpoint of this study is objective response rate (ORR), and the secondary endpoints are complete remission (CR) rate, duration of response (DoR), progression-free survival (PFS) and overall survival (OS). A total of 66 patients are enrolled mostly with diffuse large B-cell lymphoma. The ORR is 54.5% and CR rate is 31.8% meeting the primary end point. The median DoR is 12.9 months, and 1-year PFS and OS rate is 33.1% and 67.5% respectively. Adverse events (AE) are manageable with the most frequent AE being neutropenia (31.8%). Patients with MYD88 mutations, subtypes known for NF-κB activation, and high BTK expression by immunohistochemistry respond well. Overall, these results show a significant efficacy of the R2A regimen in patients with aggressive R/R B-cell NHL, with exploratory biomarkers suggesting potential associations with response. (ClinicalTrials.gov 51 identifier: NCT04094142)

Background Hepatic steatosis, which involves the excessive accumulation of lipid droplets in hepatocytes, presents a significant global health concern due to its association with obesity and metabolic disorders. Inflammation plays a crucial role in the progression of hepatic steatosis; however, the precise molecular mechanisms responsible for this process remain unknown. Methods This study investigated the involvement of the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome and the forkhead box O6 (FoxO6) transcription factor in the pathogenesis of hepatic steatosis. We monitored the NLRP3 inflammasome and lipogenesis in mice overexpressing the constitutively active (CA)-FoxO6 allele and FoxO6-null mice. In an in vitro study, we administered palmitate to liver cells overexpressing CA-FoxO6 and measured changes in lipid metabolism. Results We administered palmitate treatment to clarify the mechanisms through which FoxO6 activates cytokine interleukin (IL)-1β through the NLRP3 inflammasome. The initial experiments revealed that dephosphorylation led to palmitate-induced FoxO6 transcriptional activity. Further palmitate experiments showed increased expression of IL-1β and the hepatic NLRP3 inflammasome complex, including adaptor protein apoptotic speck protein containing a caspase recruitment domain (ASC) and pro-caspase-1. Furthermore, thioredoxin-interacting protein (TXNIP), a key regulator of cellular redox conditions upstream of the NLRP3 inflammasome, was induced by FoxO6 in the liver and HepG2 cells. Conclusion The findings of this study shed light on the molecular mechanisms underpinning the FoxO6-NLRP3 inflammasome axis in promoting inflammation and lipid accumulation in the liver.

Abstract This study examined the link between fatty liver disease (FLD) and cataracts, as previous research has suggested that FLD may contribute to metabolic syndrome, systemic inflammation, and potentially cataracts. We studied a nationwide cross-sectional cohort of the Fifth Korean National Health and Nutrition Examination Survey 2010–2011. FLD was defined as nonalcoholic FLD (NAFLD) and metabolic dysfunction-associated FLD (MAFLD). Multinomial logistic regression was utilized to investigate the relationship between cataracts and FLD after adjustment for potential confounders. Participants with cataracts had higher liver fibrosis scores, including the NAFLD fibrosis score (NFS; P

Abstract Background The epiretinal membrane (ERM) is a common retinal disorder characterized by abnormal fibrocellular tissue at the vitreomacular interface. Most patients with ERM are asymptomatic at early stages. Therefore, screening for ERM will become increasingly important. Despite the high prevalence of ERM, few deep learning studies have investigated ERM detection in the color fundus photography (CFP) domain. In this study, we built a generative model to enhance ERM detection performance in the CFP. Methods This deep learning study retrospectively collected 302 ERM and 1,250 healthy CFP data points from a healthcare center. The generative model using StyleGAN2 was trained using single-center data. EfficientNetB0 with StyleGAN2-based augmentation was validated using independent internal single-center data and external datasets. We randomly assigned healthcare center data to the development (80%) and internal validation (20%) datasets. Data from two publicly accessible sources were used as external validation datasets. Results StyleGAN2 facilitated realistic CFP synthesis with the characteristic cellophane reflex features of the ERM. The proposed method with StyleGAN2-based augmentation outperformed the typical transfer learning without a generative adversarial network. The proposed model achieved an area under the receiver operating characteristic (AUC) curve of 0.926 for internal validation. AUCs of 0.951 and 0.914 were obtained for the two external validation datasets. Compared with the deep learning model without augmentation, StyleGAN2-based augmentation improved the detection performance and contributed to the focus on the location of the ERM. Conclusions We proposed an ERM detection model by synthesizing realistic CFP images with the pathological features of ERM through generative deep learning. We believe that our deep learning framework will help achieve a more accurate detection of ERM in a limited data setting.

Inflammatory diseases are a global health problem affecting millions of people with a wide range of conditions. These diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), osteoarthritis (OA), gout, and diabetes, impose a significant burden on patients and healthcare systems. A complicated interaction between genetic variables, environmental stimuli, and dysregulated immune responses shows the complex biological foundation of various diseases. This review focuses on the molecular mechanisms underlying inflammatory diseases, including the function of inflammasomes and inflammation. We investigate the impact of environmental and genetic factors on the progression of inflammatory diseases, explore the connection between inflammation and inflammasome activation, and examine the incidence of various inflammatory diseases in relation to inflammasomes.

Abstract WDR44 prevents ciliogenesis initiation by regulating RAB11-dependent vesicle trafficking. Here, we describe male patients with missense and nonsense variants within the WD40 repeats (WDR) of WDR44, an X-linked gene product, who display ciliopathy-related developmental phenotypes that we can model in zebrafish. The patient phenotypic spectrum includes developmental delay/intellectual disability, hypotonia, distinct craniofacial features and variable presence of brain, renal, cardiac and musculoskeletal abnormalities. We demonstrate that WDR44 variants associated with more severe disease impair ciliogenesis initiation and ciliary signaling. Because WDR44 negatively regulates ciliogenesis, it was surprising that pathogenic missense variants showed reduced abundance, which we link to misfolding of WDR autonomous repeats and degradation by the proteasome. We discover that disease severity correlates with increased RAB11 binding, which we propose drives ciliogenesis initiation dysregulation. Finally, we discover interdomain interactions between the WDR and NH2-terminal region that contains the RAB11 binding domain (RBD) and show patient variants disrupt this association. This study provides new insights into WDR44 WDR structure and characterizes a new syndrome that could result from impaired ciliogenesis.

Finite element (FE) analysis of the tensile test of TWB-HPF 22MnB5 steel was performed and compared with the experimental results. To improve the accuracy of the simulation, the damage theory of FLD and ductile damage theory were used in 2D and 3D simulations. The tensile strength of 22MnB5 steel was determined under various welding heat inputs for FE simulation. Crack propagation of the welded region indicated that the fracture was observed in the base metal under normal welding conditions. Also, the crack propagated along the HAZ region due to higher heat input of the welding, and lead fractures have been highlighted as a potential complication.

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen’s efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE’s that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

Not available.