Ubiquitination-Deficient Mutations in Human Piwi Cause Male Infertility by Impairing Histone-to-Protamine Exchange during Spermiogenesis.

Genetic studies have elucidated critical roles of Piwi proteins in germline development in animals, but whether Piwi is an actual disease gene in human infertility remains unknown. We report germline mutations in human Piwi (Hiwi) in patients with azoospermia that prevent its ubiquitination and degradation. By modeling such mutations in Piwi (Miwi) knockin mice, we demonstrate that the genetic defects are directly responsible for male infertility. Mechanistically, we show that MIWI binds the histone ubiquitin ligase RNF8 in a Piwi-interacting RNA (piRNA)-independent manner, and MIWI stabilization sequesters RNF8 in the cytoplasm of late spermatids. The resulting aberrant sperm show histone retention, abnormal morphology, and severely compromised activity, which can be functionally rescued via blocking RNF8-MIWI interaction in spermatids with an RNF8-N peptide. Collectively, our findings identify Piwi as a factor in human infertility and reveal its role in regulating the histone-to-protamine exchange during spermiogenesis.

A novel KCND3 variant in the N-terminus impairs the ionic current of Kv4.3 and is associated with SCA19/22.

Spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of autosomal dominant movement disorders. Among the SCAs associated with impaired ion channel function, SCA19/22 is caused by pathogenic variants in KCND3, which encodes the voltage-gated potassium channel Kv4.3. SCA19/22 is clinically characterized by ataxia, dysarthria and oculomotor dysfunction in combination with other signs and symptoms, including mild cognitive impairment, peripheral neuropathy and pyramidal signs. The known KCND3 pathogenic variants are localized either in the transmembrane segments, the connecting loops, or the C-terminal region of Kv4.3. We have identified a novel pathogenic variant, c.455A>G (p.D152G), localized in the N-terminus of Kv4.3. It is located in the immediate neighbourhood of the T1 domain, which is responsible for multimerization with the ß-subunit KChIP2b and thus for the formation of functional heterooctamers. Electrophysiological studies showed that p.D152G does not affect channel gating, but reduces the ionic current in Kv4.3, even though the variant is not located in the transmembrane domains. Impaired channel trafficking to the plasma membrane may contribute to this effect. In a patient with a clinical picture corresponding to SCA19/22, p.D152G is the first pathogenic variant in the N-terminus of Kv4.3 to be described to date with an effect on ion channel activity.

Crystal Facet Engineering on SrTiO3 Enhances Photocatalytic Overall Water Splitting.

Single-crystal semiconductor-based photocatalysts exposing unique crystallographic facets show promising applications in energy and environmental technologies; however, crystal facet engineering through solid-state synthesis for photocatalytic overall water splitting is still challenging. Herein, we develop a novel crystal facet engineering strategy through solid-state recrystallization to synthesize uniform SrTiO3 single crystals exposing tailored {111} facets. The presynthesized low-crystalline SrTiO3 precursors enable the formation of well-defined single crystals through kinetically improved crystal structure transformation during solid-state recrystallization process. By employing subtle Al3+ ions as surface morphology modulators, the crystal surface orientation can be precisely tuned to a controlled percentage of {111} facets. The photocatalytic overall water splitting activity increases with the exposure percentage of {111} facets. Owing to the outstanding crystallinity and favorable anisotropic surface structure, the SrTiO3 single crystals with 36.6% of {111} facets lead to a 3-fold enhancement of photocatalytic hydrogen evolution rates up to 1.55 mmol·h-1 in a stoichiometric ratio of 2:1 than thermodynamically stable SrTiO3 enclosed with isotropic {100} facets.

Prognostic Significance of the Immune Microenvironment in Endometrial Cancer.

This study used artificial intelligence (AI)-based analysis to investigate the immune microenvironment in endometrial cancer (EC). We aimed to evaluate the potential of AI-based immune metrics as prognostic biomarkers. In total, 296 cases with EC were classified into 4 molecular subtypes: polymerase epsilon ultramutated (POLEmut), mismatch repair deficiency (MMRd), p53 abnormal (p53abn), and no specific molecular profile (NSMP). AI-based methods were used to evaluate the following immune metrics: total tumor-infiltrating lymphocytes (TIL), intratumoral TIL, stromal TIL, and tumor cells using Lunit SCOPE IO, as well as CD4+, CD8+, and FOXP3+ T cells using immunohistochemistry (IHC) by QuPath. These 7 immune metrics were used to perform unsupervised clustering. PD-L1 22C3 IHC expression was also evaluated. Clustering analysis demonstrated 3 distinct immune microenvironment groups: immune active, immune desert, and tumor dominant. The immune-active group was highly prevalent in POLEmut, and it was also seen in other molecular subtypes. Although the immune-desert group was more frequent in NSMP and p53mut, it was also detected in MMRd and POLEmut. POLEmut showed the highest levels of CD4+ and CD8+ T cells, total TIL, intratumoral TIL, and stromal TIL with the lowest levels of FOXP3+/CD8+ ratio. In contrast, p53abn in the immune-active group showed higher FOXP3+/CD4+ and FOXP3+/CD8+ ratios. The immune-active group was associated with favorable overall survival and recurrence-free survival. In the NSMP subtype, a significant association was observed between immune active and better recurrence-free survival. The PD-L1 22C3 combined positive score (CPS) showed significant differences among the 3 groups, with the immune-active group having the highest median CPS and frequency of CPS ≥ 1%. The immune microenvironment of EC was variable within molecular subtypes. Within the same immune microenvironment group, significant differences in immune metrics and T cell composition were observed according to molecular subtype. AI-based immune microenvironment groups served as prognostic markers in ECs, with the immune-active group associated with favorable outcomes.

The Efficacy and Safety of Radiation-Free Retrograde Intrarenal Surgery: A Prospective Multicenter-Based, Randomized, Controlled Trial.

PURPOSE: Fluoroscopy is usually required during retrograde intrarenal surgery (RIRS). Although fluoroscopy is considered necessary for effective and safe RIRS, there is growing awareness regarding radiation exposure risk to patients and surgeons. We conducted a multicenter-based, randomized, controlled trial to compare the safety and effectiveness of radiation-free (RF) RIRS with radiation-usage (RU) RIRS for kidney stone management. MATERIALS AND METHODS: From August 2020 to April 2022, patients with a unilateral kidney stone (≤20 mm) eligible for RIRS were prospectively enrolled in 5 tertiary medical centers after randomization and divided into the RF and RU groups. RIRS was performed using a flexible ureteroscope with a holmium:YAG laser. The primary end point of this study was the success rate, defined as complete stone-free or residual fragments with asymptomatic kidney stones ≤ 3 mm. The secondary end point of this study was ascertaining the safety of RF RIRS. The success rates were analyzed using a noninferiority test. RESULTS: Of the 140 consecutive randomized participants, 128 patients completed this study (RF: 63; RU: 65). The success rates (78% vs 80%, P = .8) were not significantly different between the groups. The rate of high-grade (grade 2-4) ureter injury was not significantly higher in the RF group compared to the RU group (RF = 3 [4.8%] vs RU = 2 [3.1%], P = .6). In RF RIRS, the success rate was noninferior compared to RU RIRS (the difference was 2.2% [95% CI, 0.16-0.12]). CONCLUSIONS: This study demonstrated that the surgical outcomes of RF RIRS were noninferior to RU RIRS.

A humanized ACE2 mouse model recapitulating age- and sex-dependent immunopathogenesis of COVID-19.

In the ongoing battle against coronavirus disease 2019 (COVID-19), understanding its pathogenesis and developing effective treatments remain critical challenges. The creation of animal models that closely replicate human infection stands as a critical step forward in this research. Here, we present a genetically engineered mouse model with specifically-humanized knock-in ACE2 (hiACE2) receptors. This model, featuring nine specific amino acid substitutions for enhanced interaction with the viral spike protein, enables efficient severe acute respiratory syndrome coronavirus 2 replication in respiratory organs without detectable infection in the central nervous system. Moreover, it mirrors the age- and sex-specific patterns of morbidity and mortality, as well as the immunopathological features observed in human COVID-19 cases. Our findings further demonstrate that the depletion of eosinophils significantly reduces morbidity and mortality, depending on the infecting viral dose and the sex of the host. This reduction is potentially achieved by decreasing the pathogenic contribution of eosinophil-mediated inflammation, which is strongly correlated with neutrophil activity in human patients. This underscores the model's utility in studying the immunopathological aspects of COVID-19 and represents a significant advancement in COVID-19 modeling. It offers a valuable tool for testing vaccines and therapeutics, enhancing our understanding of the disease mechanisms and potentially guiding more targeted and effective treatments.

Experimental demonstration on 400†nm-scale bandwidth optical parametric chirped-pulse amplification based on mixed cascaded crystals.

We present an optical parametric chirped-pulse amplification (OPCPA) based on mixed cascaded crystals, taking advantage of the unique parametric phase-matching of lithium triborate (LiB3O5, LBO) and yttrium calcium oxyborate ((YCa4O(BO3)3, YCOB) crystals. The OPCPA properties of LBO at 880 nm and YCOB at 750 nm are studied respectively. After amplification by two LBO and two YCOB crystals, a total signal gain of 108 and spectral bandwidth close to 400 nm is obtained. After accurate dispersion compensation with a grating-pair compressor and chirped mirror compensator, a pulse duration of 9.4 fs is obtained by a SHG-frequency-resolved optical grating (FROG). This approach will be of great significance in high energy amplifier for high peak power few-cycle laser sources.

Treatment of discoid lupus with lenalidomide and anifrolumab: Case report and review of the literature.

Discoid lupus erythematosus (DLE) is a devastating autoimmune disease with few therapies available. For patients with little to no symptom improvement with initial treatment, the literature surrounding further treatment options and their efficacy remains limited. Here we report a 46-year-old patient with lupus and refractory DLE, who failed numerous medications since her initial diagnosis in 2014. She had a robust response to lenalidomide with further improvement after adding anifrolumab (ANI), in conjunction with the standard of care hydroxychloroquine. Furthermore, she was able to taper off steroids without interval flares. The patient has not experienced any major infections since the initiation of treatment. No previous case reports describing outcomes of lenalidomide and ANI have been reported, yet the combinational approach has potential. Future clinical trials are needed to investigate the safety of the combination of lenalidomide and ANI in lupus patients with refractory DLE.

Dual add-on therapy of gemigliptin and dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin alone: The SOLUTION 2 study.

AIM: To evaluate the efficacy and safety of gemigliptin and dapagliflozin dual add-on therapy (GEMI + DAPA) to metformin in type 2 diabetes (T2D) patients who had inadequate glycaemic control on metformin alone, compared with a single add-on of either gemigliptin (GEMI) or dapagliflozin (DAPA) to metformin. MATERIALS AND METHODS: In this randomized, double-blind, double-dummy, active-controlled, parallel-group, phase 3 study, 469 T2D patients treated with a stable dose of metformin for 8 weeks or longer were randomized to receive GEMI + DAPA (n = 157) and either GEMI (n = 156) or DAPA (n = 156). The primary endpoint was change in HbA1c levels from baseline at week 24. RESULTS: Baseline characteristics including body mass index and T2D duration were similar among groups. At week 24, the least square mean changes in HbA1c from baseline were -1.34% with GEMI + DAPA, -0.90% with GEMI (difference between GEMI + DAPA vs. GEMI -0.44% [95% confidence interval {CI}: -0.58% to -0.31%], P < .01) and -0.78% with DAPA (difference between GEMI + DAPA vs. DAPA -0.56% [95% CI: -0.69% to -0.42%], P < .01). Both upper CIs were less than 0, demonstrating the superiority of GEMI + DAPA for lowering HbA1c. The rates of responders achieving HbA1c less than 7% and less than 6.5% were greater with GEMI + DAPA (84.9%, 56.6%) than with GEMI (55.3%, 32.2%) and DAPA (49.3%, 15.3%). The incidence rate of adverse events was similar across groups, with low incidence rates of hypoglycaemia, urinary tract infection and genital infection. CONCLUSIONS: These results suggest that the addition of GEMI + DAPA to metformin as triple combination therapy was effective, safe and well-tolerated, especially for T2D patients who experienced poor glycaemic control on metformin alone.

Efficacy and safety of a fixed-dose combination of dapagliflozin and linagliptin (AJU-A51) in patients with type 2 diabetes mellitus: A multicentre, randomized, double-blind, parallel-group, placebo-controlled phase III study.

AIMS: To evaluate the efficacy and safety of add-on dapagliflozin in patients with type 2 diabetes mellitus (T2D) who had inadequate glycaemic control with metformin and linagliptin. MATERIALS AND METHODS: A total of 235 patients with inadequate response to metformin (≥1000 mg/day) plus linagliptin (5 mg/day) were randomized to receive either dapagliflozin/linagliptin fixed-dose combination (FDC [AJU-A51]) 10/5 mg/day (n = 117) or linagliptin 5 mg plus placebo (n = 118) for 24 weeks. After the main treatment period, patients who received linagliptin plus placebo were treated with AJU-A51 for an additional 28 weeks. Change in glycated haemoglobin (HbA1c) from baseline to Week 24 was the primary endpoint. RESULTS: AJU-A51 significantly reduced HbA1c levels (from 7.93% ± 0.82% to 7.11% ± 0.61%) compared with linagliptin plus placebo (from 7.80% ± 0.71% to 7.87% ± 0.94%), with a least squares mean difference of -0.88% (95% confidence interval -1.07 to -0.68; p < 0.0001) at 24 weeks. The AJU-A51 group had a significantly higher proportion of patients who achieved HbA1c <7.0% at Week 24 than the control group (44.8% vs. 18.6%; p < 0.001). The AJU-A51 group maintained glycaemic efficacy up to 52 weeks, whereas the control group showed a substantial reduction in HbA1c after switching to AJU-A51 in the extension study period. Both groups had similar incidence of treatment-emergent and serious adverse events, and no cases of symptomatic hypoglycaemia were reported. CONCLUSIONS: Dapagliflozin and linagliptin FDC (AJU-A51) showed potent glucose-lowering effects, with good tolerability, in patients with T2D who had poor glycaemic control on metformin and linagliptin (ClinicalTrials.gov [NCT06329674]).

Synthesis of unsymmetrical phosphorus disulfides.

A sulfur-mediated umpolung strategy employing N-thiosuccinimides and (EtO)2P(O)SH has been developed to synthesize unsymmetrical organophosphorus disulfides (P(O)-S-S motif). A pronucleophile (EtO)2P(O)SH, Brønsted acid and phosphorothioate nucleophile, converts N-thiosuccinimides into unsymmetrical phosphorus disulfides. This protocol achieves catalyst- and additive-free reaction conditions, uses a renewable solvent (EtOH), and avoids harsh reagents.

p16 Immunohistochemical Patterns in Triple-Negative Breast Cancer: Clinical and Genomic Similarities of the p16 Diffuse Pattern to pRB Deficiency.

INTRODUCTION: Triple-negative breast cancer (TNBC) is associated with alterations in the retinoblastoma pathway. As a consequence of retinoblastoma protein (pRB) loss, compensatory upregulation of p16 occurs due to the loss of phosphorylated pRB-mediated negative feedback on p16 expression. The aim of this study is to investigate the clinicopathological and genomic characteristics associated with the diffuse pattern of p16 immunohistochemistry (IHC) in TNBC. METHODS: The study analyzed surgically resected TNBC for whole-exome sequencing in 113 cases and for cDNA microarray in 144 cases. The p16 IHC results were classified into two patterns: diffuse and negative/mosaic. RESULTS: In the entire cohort (n = 257), the diffuse pattern of p16 IHC was observed in 123 (47.9%) patients and the negative/mosaic pattern in 134 (52.1%). Biallelic RB1 inactivation was observed in 14.3% of patients with the diffuse pattern. The diffuse pattern of p16 IHC showed more frequent RB1 alterations and cell cycle progression signatures, a higher Ki-67 labeling index, more frequent chromosome segment copy number changes, a higher frequency of homologous recombination deficiency high, and immune-related signatures. PIK3CA mutations were more frequent in the negative/mosaic pattern. CCND1 amplification was identified in 5 cases, all with the negative/mosaic pattern. CONCLUSION: In TNBC, the diffuse p16 pattern shows clinical and genomic similarities to pRB-deficient tumors, suggesting shared characteristics. This suggests that p16 IHC testing may provide new therapeutic approaches, underscoring its potential clinical importance.

Improvement of lower urinary tract dysfunction by a monoacylglycerol lipase inhibitor in mice with spinal cord injury.

AIMS: Activation of the endocannabinoid system by monoacylglycerol lipase (MAGL) blockade may affect the lower urinary tract function. We investigated the effect of an MAGL inhibitor, MJN110, on neurogenic lower urinary tract dysfunction (LUTD) in the mouse model of spinal cord injury (SCI). METHODS: Female C57BL/6 mice that underwent spinal cord transection at T8-10 level were divided into three groups consisting of (1) vehicle-treated SCI mice, (2) 5 mg/kg, or (3) 10 mg/kg of MJN110-treated SCI mice. MJN110 and vehicle were administered intraperitoneally for 7 days from 4 weeks after spinal cord transection. We then conducted awake cystometrograms and compared urodynamic parameters between three groups. The expression of cannabinoid (CB) receptors, TRP receptors, and inflammatory cytokines in L6-S1 dorsal root ganglia (DRG) or the bladder mucosa were evaluated and compared among three groups. Changes in the level of serum 2-arachidonoylglycerol (2-AG) and bladder MAGL were also evaluated. RESULTS: In the cystometrogram, detrusor overactivity (DO) parameters, such as the number of nonvoiding contraction (NVC), a ratio of time to the 1st NVC to intercontraction interval (ICI), and NVC integrals were improved by MJN110 treatment, and some effects were dose dependent. Although MJN110 did not improve voiding efficiency, it decreased bladder capacity, ICI, and residual urine volume compared to vehicle injection. MJN110 treatment groups had lower CB2, TRPV1, TRPA1, and inflammatory cytokines mRNA levels in DRG and bladder mucosa. Serum 2-AG was increased, and bladder MAGL was decreased after MAGL inhibitor treatment. CONCLUSIONS: MAGL inhibition improved LUTD including attenuation of DO after SCI. Thus, MAGL can be a therapeutic target for neurogenic LUTD after SCI.

Sex differences in lower urinary tract function in mice with or without spinal cord injury.

OBJECTIVES: We examined sex differences of lower urinary tract function and molecular mechanisms in mice with and without spinal cord injury (SCI). METHODS: SCI was induced by Th8-9 spinal cord transection in male and female mice. We evaluated cystometrograms (CMG) and electromyography (EMG) of external urethral sphincter (EUS) at 6 weeks after SCI in spinal intact (SI) and SCI mice. The mRNA levels of Piezo2 and TRPV1 were measured in L6-S1 dorsal root ganglia (DRG). Protein levels of nerve growth factor (NGF) in the bladder mucosa was evaluated using an enzyme-linked immunosorbent assay. RESULTS: Sex differences were found in the EUS behavior during voiding as voiding events in female mice with or without SCI occurred during EUS relaxation periods without EUS bursting activity whereas male mice with or without SCI urinated during EUS bursting activity in EMG recordings. In both sexes, SCI decreased voiding efficiency along with increased tonic EUS activities evident as reduced EUS relaxation time in females and longer active periods of EUS bursting activity in males. mRNA levels of Piezo2 and TRPV1 of DRG in male and female SCI mice were significantly upregulated compared with SI mice. NGF in the bladder mucosa showed a significant increase in male and female SCI mice compared with SI mice. However, there were no significant differences in Piezo2 or TRPV1 levels in DRG or NGF protein levels in the bladder mucosa between male and female SCI mice. CONCLUSIONS: We demonstrated that female and male mice voided during EUS relaxation and EUS bursting activity, respectively. Also, upregulation of TRPV1 and Piezo2 in L6-S1 DRG and NGF in the bladder could be involved in SCI-induced lower urinary tract dysfunction in both sexes of mice.

Brigatinib, a newly discovered AXL inhibitor, suppresses AXL-mediated acquired resistance to osimertinib in EGFR-mutated non-small cell lung cancer.

In addition to the classical resistance mechanisms, receptor tyrosine-protein kinase AXL is a main mechanism of resistance to third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) osimertinib in EGFR-mutated non-small cell lung cancer (NSCLC). Developing an effective AXL inhibitor is important to sensitize osimertinib in clinical application. In this study we assessed the efficacy of brigatinib, a second-generation of anaplastic lymphoma kinase (ALK)-TKI, as a novel AXL inhibitor, in overcoming acquired resistance to osimertinib induced by AXL activation. We established an AXL-overexpression NSCLC cell line and conducted high-throughput screening of a small molecule chemical library containing 510 anti-tumor drugs. We found that brigatinib potently inhibited AXL expression, and that brigatinib (0.5 µM) significantly enhanced the anti-tumor efficacy of osimertinib (1 µM) in AXL-mediated osimertinib-resistant NSCLC cell lines in vitro. We demonstrated that brigatinib had a potential ability to bind AXL kinase protein and further inhibit its downstream pathways in NSCLC cell lines. Furthermore, we revealed that brigatinib might decrease AXL expression through increasing K48-linked ubiquitination of AXL and promoting AXL degradation in HCC827OR cells and PC-9OR cells. In AXL-high expression osimertinib-resistant PC-9OR and HCC827OR cells derived xenograft mouse models, administration of osimertinib (10 mg·kg-1·d-1) alone for 3 weeks had no effect, and administration of brigatinib (25 mg·kg-1·d-1) alone caused a minor inhibition on the tumor growth; whereas combination of osimertinib and brigatinib caused marked tumor shrinkages. We concluded that brigatinib may be a promising clinical strategy for enhancing osimertinib efficacy in AXL-mediated osimertinib-resistant NSCLC patients.

The establishment of diseased human whole organ model by normothermic machine perfusion technique: Principle of concept.

BACKGROUND: The global incidence of liver diseases is rising, yet there remains a dearth of precise research models to mimic these diseases. The use of normothermic machine perfusion (NMP) to study diseased livers recovered from liver transplantation (LT) recipients presents a promising avenue. Accordingly, we have developed a machine perfusion system tailored specifically for the human whole diseased livers and present our experience from the NMP of diseased livers. METHODS: Six diseased livers recovered from LT recipients with different diagnoses were collected. The diseased livers were connected to the machine perfusion system that circulated tailored perfusate, providing oxygen and nutrients. The pressure and flow of the system were recorded, and blood gas analysis and laboratory tests of perfusate and bile were examined to analyze the function of the diseased livers. Liver tissues before and after NMP were collected for histological analysis. RESULTS: Experiments showed that the system maintained the diseased livers in a physiological state, ensuring stable hemodynamics and a suitable partial pressure of oxygen and carbon dioxide. The results of blood gas analysis and laboratory tests demonstrated a restoration and sustenance of metabolism with minimal damage. Notably, a majority of the diseased livers exhibited bile production continuously, signifying their vivid functional integrity. The pathological characteristics remained stable before and after NMP. CONCLUSION: We successfully established the machine perfusion system tailored specifically for diseased human whole livers. Through the application of this system, we have developed a novel in vitro model that faithfully recapitulates the main features of human liver disease. This model holds immense promise as an advanced disease modeling platform, offering profound insights into liver diseases and potential implications for research and therapeutic development.

High remnant-cholesterol levels increase the risk for end-stage renal disease: a nationwide, population-based, cohort study.

BACKGROUND: The effect of remnant-cholesterol (remnant-C) on incident end-stage renal disease (ESRD) has not been studied longitudinally. This retrospective cohort study evaluated the association between remnant-C and the development of ESRD in a nationwide Korean cohort. METHODS: Participants in a National Health Insurance Service health examination (n = 3,856,985) were followed up until the onset of ESRD. The median duration of follow-up was 10.3 years. The Martin-Hopkins equation was used to determine low-density lipoprotein cholesterol (LDL-C) levels from directly measured triglyceride, high-density lipoprotein cholesterol (HDL-C), and total cholesterol levels. Remnant-C levels were determined by subtracting HDL-C and LDL-C from total cholesterol. The risk for incident ESRD was calculated for each quartile of remnant-C, adjusting for conventional risk factors such as baseline renal function, comorbidities, and total cholesterol levels. RESULTS: ESRD developed in 11,073 (0.29%) participants. The risk for ESRD exhibited a gradual increase according to higher levels of remnant-C, with a 61% increased risk in the highest quartile than in the lowest (hazard ratio [HR] 1.61 [95% confidence interval (CI) 1.50-1.72]). The elevated risk for ESRD in the highest quartile versus the lowest quartile was more prominent in younger than in older subjects (20-29 years, HR 4.07 [95% CI 2.85-5.83]; 30-39 years, HR 2.39 [95% CI 1.83-3.13]; ≥ 70 years, HR 1.32 [95% CI 1.16-1.51]). In addition, the increased risk for ESRD related to higher remnant-C levels was greater in females than in males. CONCLUSIONS: Independent of conventional risk factors, remnant-C levels were positively associated with incident ESRD, particularly in younger populations and adult females. Reducing remnant-C levels may be a novel preventive strategy against ESRD.

Spontaneous clinical remission of Nagashima-type palmoplantar keratoderma in a patient of Korean descent with a heterozygous SERPINB7 mutation.

Nagashima-type palmoplantar keratoderma (NPPK) is an autosomal recessive form of diffuse palmoplantar keratoderma (PPK) characterized by thickening and redness of palms and/or soles. In this report, we describe a female patient of Korean descent who had clinical remission of her adult-onset NPPK. To our knowledge, she is the first reported heterozygous SERBINB7 mutation carrier to present with classic NPPK who achieved spontaneous clinical remission.

Establishment of an inspection standard for decomposition and methane production rates of organic waste co-digestion facilities in Korea.

Domestic organic waste resources have increased over the past decade and treatment of this waste via co-digested biogasification facilities is increasing annually. However, inspection standards for such facilities are not well-established. Herein, we aimed to derive calculation formulas and factors related to organic matter decomposition efficiency and methane production rate in accordance with waste treatment facility inspection standards. We also aimed to determine the optimum waste mixing ratio. Sample (field) surveys of 18 treatment facilities and complete enumeration of 110 facilities were conducted. Calculation formulas and factors were derived using the survey data and biochemical methane potential (BMP) test. The calculated coefficients derived through the BMP test were 0.512 m3 CH4/kgVSin for food waste, 0.601 m3 CH4/kgVSin for livestock manure, and 0.382 m3 CH4/kgVSin for sewage sludge. The final derived calculation factors were 65.0% for food waste, 36.0% for livestock manure, and 20.0% for sewage sludge for organic matter decomposition efficiency, and 0.380 m3 CH4/kgVSin for food waste, 0.27 m3 CH4/kgVSin for livestock manure, and 0.140 m3 CH4/kgVSin for sewage sludge for methane production rates. The derived effective capacity calculation factors can be utilized in future waste treatment facility inspection methods by aiding in the establishment of appropriate inspection standards for co-digested biogasification facilities other than single food waste treatment facilities. In addition, the optimum mixing ratio can be used as design data for co-digested biogasification facilities.