Coronary artery disease risk prediction by combined stratification of low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol levels across different glucose statuses.

AIM: To investigate the association between low-density lipoprotein-cholesterol (LDL-C) levels and coronary artery disease (CAD) incidence based on combining high-density lipoprotein-cholesterol (HDL-C) levels and glucose status. MATERIALS AND METHODS: In this retrospective cohort study, we used data from a nationwide claims database (1,524,289 individuals without a history of CAD or familial hypercholesterolaemia; 2008-2019). Cox proportional hazards modelling identified the risk of incident CAD by a novel combination of four HDL-C levels, seven LDL-C levels and glucose status. RESULTS: During the follow-up period (mean: 5.5 years), 8301 (0.99/1000 person-years) events occurred. The risk of CAD increased from lower LDL-C levels accompanied by lower HDL-C levels regardless of the glucose status. Using the most favourable levels of HDL-C and LDL-C (i.e. 60-99 mg/dL and <80 mg/dL, respectively) as references, the hazard ratios (95% confidence interval) for the group with HDL-C levels <40 mg/dL and LDL-C levels <80 mg/dL were 2.74 (1.47-5.11), 2.52 (1.30-4.91) and 2.85 (1.68-4.84) for normoglycaemia, borderline glycaemia and diabetes, respectively. Comparison of the most favourable levels of HDL-C and LDL-C with their least favourable levels (i.e. <40 mg/dL and 180-199 mg/dL, respectively) revealed that the risk of new-onset CAD exhibited a 19-, nine- and seven-fold increase in individuals with normoglycaemia, borderline glycaemia and diabetes, respectively. CONCLUSIONS: To prevent CAD, LDL-C levels should be strictly controlled in patients with low HDL-C levels regardless of glucose tolerance. Individualized treatment, which involves setting target LDL-C levels based on glucose tolerance and HDL-C values, is required.

Arginine vasopressin deficiency onset after COVID-19 vaccination with positive anti-rabphilin-3A antibodies: a case report and literature review.

BACKGROUND: Arginine vasopressin deficiency (AVP-D) can occur due to various conditions, so clarifying its cause is important for deciding treatment strategy. Although several cases of AVP-D following coronavirus disease 2019(COVID-19) infection or COVID-19 vaccination have been reported, the diagnosis of the underlying disease has not been reported in most cases. CASE PRESENTATION: A 75-year-old woman who presented with polydipsia and polyuria 9 weeks after contracting COVID-19 and 5 weeks after receiving the SARS-CoV-2 vaccination, leading to the final diagnosis of AVP-D 8 months after the first appearance of symptoms. Interestingly, pituitary magnetic resonance imaging (MRI) still revealed stalk enlargement frequently observed in patients with SARS-CoV-2 vaccination-induced AVP-D. Although this finding could not rule out any malignancies, we additionally measured anti-rabphilin-3A antibodies, a known marker for lymphocytic infundibulo-neurohypophysitis (LINH), and found that the results were positive, strongly suggesting LINH as the cause of this disease. Thus, we avoided pituitary biopsy. At the follow-up MRI conducted 12 months after the initial consultation, enlargement of the pituitary stalk was still observed. CONCLUSION: We experienced a case with LINH probably induced by SARS-CoV-2 vaccination. In SARS-CoV-2 vaccination-related LINH, unlike typical LINH, there is a possibility of persistent pituitary stalk enlargement on MRI images for an extended period, posing challenges in differential diagnosis from other conditions. Pituitary stalk enlargement and positive anti-rabphilin-3A antibodies may help in the diagnosis of AVP-D induced by SARS-CoV-2 vaccination.

Changes in ocular blood flow in patients with neovascular age-related macular degeneration after intravitreal injection of ranibizumab biosimilar and brolucizumab.

PURPOSE: To assess ocular blood flow (OBF) changes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal injections of ranibizumab biosimilar (IVRbs) or brolucizumab (IVBr). METHODS: This retrospective longitudinal study included 43 eyes of 43 patients (74.5 ± 9.8 years old, male to female ratio 31:12) with nAMD treated with IVBr (29 eyes) or IVRbs (14 eyes). OBF in the optic nerve head (ONH) and choroid (Ch) was measured with laser speckle flowgraphy (Softcare Co., Ltd., Fukutsu, Japan) before and one month after treatment. Changes in mean blur rate (MBR) before and after each treatment were tested using Wilcoxon's signed-rank tests and mixed-effect models for repeated measures. RESULTS: In the IVBr group, MBR was significantly reduced in both the ONH and Ch (p < 0.01). In contrast, the IVRbs group showed no significant change in MBR in either the ONH or Ch (p = 0.56, p = 1). The linear mixed effect model showed a significant interaction between time and anti-VEGF drugs for MBR in both the ONH and Ch (ONH: p = 0.04; Ch: p = 0.002). A post hoc pairwise comparison of estimated marginal means showed that MBR decreased significantly only after IVBr (p < 0.001). CONCLUSION: Our findings suggest that the short-term impact on OBF varies depending on the drug used for nAMD.

Baseline characteristics associated with the incidence of intraocular inflammation after the intravitreous injection of brolucizumab.

PURPOSE: To investigate baseline characteristics associated with the incidence of intraocular inflammation (IOI) after the intravitreal injection of brolucizumab (IVBr) for the treatment of neovascular age-related macular degeneration (nAMD). METHODS: This retrospective study included 66 eyes of 62 consecutive patients with nAMD who received IVBr (18 eyes were treatment naïve and 48 eyes had switched from other anti-vascular endothelial growth factor [VEGF] therapy). Baseline clinical characteristics were compared in non-IOI and IOI groups. RESULTS: Although a dry macula was achieved at a high rate even 6 months after IVBr, IOI occurred in 8 of 66 eyes (12.1%; all had switched therapy) during the study period. Baseline characteristics including age, sex, nAMD type, lens status, visual acuity, central macular thickness, and a history of diabetes did not differ between the groups. The number of previous anti-VEGF injections before IVBr was greater in the IOI group (P = 0.004), and the ratio of patients with a laser flare-cell photometry (LFCP) value over 15 photon count per millisecond (pc/ms) was higher in the IOI group (P = 0.017). Multivariate logistic regression analysis showed that a greater number of previous anti-VEGF injections (odds ratio [OR]: 1.12, P = 0.006; area under the curve: 0.82, cut-off score: 14.0) and an LFCP value over 15 pc/ms (OR: 81.6, P = 0.031) were significantly associated with the incidence of IOI after IVBr. CONCLUSION: A number of previous anti-VEGF injections greater than 14 and an LFCP value more than 15 pc/ms might be useful predictors of the incidence of IOI after IVBr in eyes with nAMD.

Finding the direct optimal RNA barrier energy and improving pathways with an arbitrary energy model.

MOTIVATION: RNA folding kinetics plays an important role in the biological functions of RNA molecules. An important goal in the investigation of the kinetic behavior of RNAs is to find the folding pathway with the lowest energy barrier. For this purpose, most of the existing methods use heuristics because the number of possible pathways is huge even if only the shortest (direct) folding pathways are considered. RESULTS: In this study, we propose a new method using a best-first search strategy to efficiently compute the exact solution of the minimum barrier energy of direct pathways. Using our method, we can find the exact direct pathways within a Hamming distance of 20, whereas the previous methods even miss the exact short pathways. Moreover, our method can be used to improve the pathways found by existing methods for exploring indirect pathways. AVAILABILITY AND IMPLEMENTATION: The source code and datasets created and used in this research are available at https://github.com/eukaryo/czno. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

RintC: fast and accuracy-aware decomposition of distributions of RNA secondary structures with extended logsumexp.

BACKGROUND: Analysis of secondary structures is essential for understanding the functions of RNAs. Because RNA molecules thermally fluctuate, it is necessary to analyze the probability distributions of their secondary structures. Existing methods, however, are not applicable to long RNAs owing to their high computational complexity. Additionally, previous research has suffered from two numerical difficulties: overflow and significant numerical errors. RESULT: In this research, we reduced the computational complexity of calculating the landscape of the probability distribution of secondary structures by introducing a maximum-span constraint. In addition, we resolved numerical computation problems through two techniques: extended logsumexp and accuracy-guaranteed numerical computation. We analyzed the stability of the secondary structures of 16S ribosomal RNAs at various temperatures without overflow. The results obtained are consistent with previous research on thermophilic bacteria, suggesting that our method is applicable in thermal stability analysis. Furthermore, we quantitatively assessed numerical stability using our method.. CONCLUSION: These results demonstrate that the proposed method is applicable to long RNAs..

A Case of Type 1 Diabetes Mellitus With Endogenous Insulin Secretory Depletion Confirmed in Two Weeks.

Type 1 diabetes mellitus (T1DM) is manifested as a decrease in endogenous insulin secretion. With this report, we present a case of T1DM where a rapid decline in insulin secretion was observed in a short span of time. A 56-year-old female patient presented with cold-like symptoms with subsequent dry mouth and malaise to the hospital. Three weeks later, she was diagnosed with diabetic ketoacidosis based on the presence of hyperglycemia, metabolic acidosis, and positive ketone bodies. Her serum connecting peptide (CPR) levels substantially decreased (1.31 to 0.19 ng/mL after two weeks) and she was eventually diagnosed with T1DM. We hypothesized that a subtype T1DM with a longer beta cell loss rate than conventional fulminant type 1 diabetes was involved. This subtype showed characteristics of immune checkpoint inhibitor-associated fulminant type 1 diabetes and is suggested to exist among those diagnosed with conventional acute-onset type 1 diabetes. Finally, we recommend that diabetic ketoacidosis of unknown etiology should be investigated for the concurrent presence of T1DM.

GenerRNA: A generative pre-trained language model for de novo RNA design.

The design of RNA plays a crucial role in developing RNA vaccines, nucleic acid therapeutics, and innovative biotechnological tools. However, existing techniques frequently lack versatility across various tasks and are dependent on pre-defined secondary structure or other prior knowledge. To address these limitations, we introduce GenerRNA, a Transformer-based model inspired by the success of large language models (LLMs) in protein and molecule generation. GenerRNA is pre-trained on large-scale RNA sequences and capable of generating novel RNA sequences with stable secondary structures, while ensuring distinctiveness from existing sequences, thereby expanding our exploration of the RNA space. Moreover, GenerRNA can be fine-tuned on smaller, specialized datasets for specific subtasks, enabling the generation of RNAs with desired functionalities or properties without requiring any prior knowledge input. As a demonstration, we fine-tuned GenerRNA and successfully generated novel RNA sequences exhibiting high affinity for target proteins. Our work is the first application of a generative language model to RNA generation, presenting an innovative approach to RNA design.

Adrenocortical Adenoma With Protrusion Into the Inferior Vena Cava Initially Suspected to Be Adrenocortical Carcinoma.

Adrenal tumors with invasion into the inferior vena cava (IVC) are typically malignant. Here, we present a case of adrenocortical adenoma with protrusion into the IVC. A 70-year-old man was referred to our hospital after his magnetic resonance imaging scan of the abdomen coincidently revealed a right adrenal tumor invading the IVC. We suspected an aggressive adrenal carcinoma and tumor resection was performed. However, all 3 existing pathological criteria (Weiss, modified Weiss, and Helsinki) suggested the tumor was benign. Immunohistochemistry for CD31 showed the tumor inside the central adrenal vein (CAV), right adrenal vein (RAV), and IVC was entirely covered with CD31-positive vascular endothelial cells. The CAV is known to sometimes lack smooth muscle in its walls and normal adrenocortical cells covered by endothelial cells sometimes protrude into the CAV from this gap. These findings suggest that this tumor likely protruded into the IVC by pushing against the CAV wall, rather than by invasion into the vascular wall. In the case with adrenal tumors protruding into the IVC, the fact that the tumor surface was covered by vascular endothelial cells was considered supportive of its benign nature.

Predictors of postoperative storage symptoms in male patients with lower urinary tract symptoms: A retrospective analysis of prostate surgery for benign prostatic enlargement.

OBJECTIVES: This study investigated the effects of prostate surgery on storage symptoms in male patients with lower urinary tract symptoms (LUTS) from benign prostatic enlargement (BPE). This study aimed to identify patient characteristics associated with improved, unchanged, and deteriorated post-surgical storage symptoms and to identify the risk factors for non-improvement or deterioration. METHODS: A retrospective analysis of 586 prostate surgeries performed between 2016 and 2022 at Yokosuka Kyosai Hospital was conducted on patients with LUTS and at least one storage symptom preoperatively. Patients with active urinary tract infection, prostate/bladder cancer, urethral strictures, or dementia were excluded. The study enrolled 230 patients and assessed storage symptoms using the International Prostate Symptom Score (IPSS). RESULTS: Overall, storage symptoms improved, remained unchanged, and deteriorated in 87.0%, 5.7%, and 7.4% of patients, respectively. The patients in the deteriorated group were significantly older, whereas those in the no-change group had smaller prostate volumes. Patient-reported outcome scores (IPSS, IPSS-QoL, and BII) were significantly higher in the improved group. The predictors of non-improvement included low IPSS storage score, cardiovascular disease, and diabetes mellitus. Predictors of deterioration included advanced age and low IPSS storage score. CONCLUSIONS: Patients with severe LUTS showed greater postoperative improvement in storage symptoms. A low IPSS storage score predicted non-improvement and deterioration. Advanced age, low IPSS storage score, and a history of cardiovascular disease and diabetes mellitus were identified as key predictors. Awareness of these factors may guide preoperative counseling and improve decision-making in prostate surgery, ensuring more personalized and effective treatment strategies.

Strongly solved Ostle: calculating a strong solution helps compose high-quality puzzles for recent games.

Pure strategy board games such as chess are popular intellectual activities, and solving them is a challenging task in computer science. In addition to traditional games, many new board games have gained popularity in recent years. Ostle is one such unsolved game published in 2017. It is based on simple rules but is highly competitive. It is a two-player zero-sum game with perfect information in which the game-theoretical values of all game states can be obtained. In this study, we strongly solved Ostle by retrograde analysis. Utilizing various known techniques, including bitboards and succinct indexable dictionaries, significantly reduced the memory consumption in the analyses. We confirmed that the initial position is a draw and found some fundamental properties of Ostle. Additionally, we manually composed a tactical Ostle puzzle with the help of extracted outputs of the analyses. The result demonstrates that solving recent games provided helpful information to compose high-quality problems.

Predictive factors for the success of trial without catheter for men with urinary retention.

OBJECTIVE: To investigate the trial of spontaneous urination without catheter (TWOC) outcomes for men with acute urinary retention, determine successful TWOC predictors, and evaluate the impact of add-on medication therapy on TWOC. METHODS: This retrospective study included men with acute urinary retention and post-void residual (PVR) >250 mL who underwent TWOC between July 2009 and July 2019. Patients were divided into a medicated group who received alpha1 blocker on urinary retention diagnosis and a naïve group who did not. The trial was defined as unsuccessful if the PVR was >150 mL or if the patient experienced difficulty emptying their bladder with abdominal discomfort or pain, and a transurethral catheter was reinserted. RESULTS: Among 576 men with urinary retention, 269 (46.7%) constituted the medicated group and 307 (53.3%) the naïve. The naïve group comprised more elderly patients (P = 0.010) with higher Eastern Cooperative Oncology Group performance status (PS) (P = 0.001) and smaller prostate volume (P = 0.028) than the other. In the medicated group, 153 men received additional oral medication before TWOC to increase the success rate. There were significant age differences (P = 0.041) in the medicated group and significant median PS differences (P = 0.010) in the naïve group between the successful and unsuccessful outcomes of TWOC. The multivariate logistic regression model demonstrated that age <80 years in medicated patients (P = 0.042, odds ratio [OR] 1.701) and PS <2 in naïve patients (P = 0.001, OR 2.710) were significant independent predictors of successful TWOC outcomes. CONCLUSIONS: This is the first study classifying patients with urinary retention according to medication status. Both medicated and naïve groups had different patient backgrounds and TWOC outcome predictors, suggesting a discrepant etiology behind urinary retention. Hence, acute urinary retention management in men should vary based on medication status for male lower urinary tract symptoms when urinary retention is diagnosed.

Detection of Euglycemic Diabetic Ketoacidosis During Thoracic Surgery 75 Hours After Empagliflozin Discontinuation.

Euglycemic diabetic ketoacidosis (eDKA) has been increasingly reported as an adverse event of sodium-glucose cotransporter 2 inhibitors (SGLT2i), and the accompanying information on the drug recommends discontinuation three days prior to scheduled surgery. We present a case of a 50-year-old woman who developed eDKA during surgery for a metastatic lung tumor 75 hours after discontinuing SGLT2i. In this case, the onset of eDKA was detected using intraoperative blood gas analysis and urinary ketone measurements. Hence, perioperative eDKA can occur even after three or more days of SGLT2i withdrawal.

[A CASE OF RENAL CELL CARCINOMA WITH SMALL INTESTINE METASTASIS DURING NIVOLUMAB PLUS IPILIMUMAB].

A 71-year-old man with a history of hoarseness and right upper extremity numbness was referred to our department for evaluation of an intrathoracic mass that was detected on chest radiography and a right kidney tumor observed on computed tomography (CT). Histopathological examination of percutaneous kidney biopsy and bronchoscopic lung biopsy specimens revealed renal clear cell carcinoma with multiple lung metastases. The patient showed a poor risk based on the International Metastatic renal cell carcinoma Database Consortium score, and nivolumab plus ipilimumab were initiated as first-line therapy. His symptoms gradually improved, following four courses of nivolumab plus ipilimumab treatment, and CT revealed shrinkage of all lesions. However, he developed diarrhea, rash, anemia, and elevated serum C-reactive protein levels (CRP) following this therapy. Diarrhea and rash were considered immune-related adverse events, and he was treated with oral prednisolone and topical corticosteroid. Nivolumab administration was discontinued because anemia worsened together with elevated serum CRP levels despite improvement in diarrhea. He subsequently developed constipation and abdominal bloating, following further treatment for 4 months. CT revealed intestinal tumor-induced intussusception, necessitating partial resection of the small intestinal tumor, which was histopathologically diagnosed as metastases. Both anemia and elevated CRP improved postoperatively. Currently, all metastatic lesions other than the resected intestine have continued to respond to treatment over 12 months after initiation of nivolumab plus ipilimumab therapy.

[A CASE OF SMALL CELL CARCINOMA IN A DIVERTICULUM OF THE BLADDER].

An 80-year-old man was referred to our hospital with a complaint of acute urinary retention due to hematuria. Cystoscopy revealed a broad-based tumor arising in a diverticulum on the right lateral wall of the bladder. Transurethral resection of the bladder tumor (TURBT) was performed immediately. The pathological diagnosis was small-cell carcinoma without any urothelial carcinomas, and clinical examination revealed a clinical stage of T3b, N0, M0. Thus, 3 courses of neoadjuvant chemotherapy with cisplatin and irinotecan were administered. Chemotherapy resulted in tumor shrinkage, and partial cystectomy was performed under a diagnosis of stage pT3aN0M0 bladder cancer in the diverticulum. The patient is alive without any evidence of tumor recurrence at 13 months after the operation. To our knowledge, this is the first case report in Japan of small-cell carcinoma in a diverticulum of the urinary bladder, for which partial cystectomy was performed after chemotherapy.

[NON-SPECIFIC GRANULOMATOUS PROSTATITIS: A CASE REPORT].

We report non-specific granulomatous prostatitis in a 58-year-old man who visited a Urology clinic with fever and dysuria. Digital rectal examination revealed prostatic tenderness, and laboratory examination of the urinary sediment revealed pyuria. Thus, he was diagnosed with acute bacterial prostatitis and treated with antibiotics. He remained symptomatic despite treatment; therefore, he was referred to our hospital. A second digital rectal examination (performed at our hospital) revealed stony hard nodules in the prostate and an irregularity of its surface. Moreover, magnetic resonance imaging (MRI) suggested a prostate cancer. We performed a transperineal needle biopsy, which revealed only non-specific inflammatory cells without any evidence of neoplasm in the specimen. Therefore, a definitive diagnosis could not be established. Nevertheless, he continued to show a high index of suspicion for prostatic malignancy based on his clinical findings. Therefore, we performed a transurethral resection of the prostate and a transrectal biopsy to obtain more specimens. Microscopic findings revealed granulomatous prostatitis without any evidence of prostate carcinoma. Notably, an MRI demonstrated remarkable shrinkage of the prostate 3 months after the diagnosis. Non-specific granulomatous prostatitis is a rare inflammatory disease. Because it is difficult to differentiate this disease from prostatic neoplasms based on clinical findings or imaging modalities such as MRI, a few reports have described performing a radical prostatectomy in patients. This disease usually demonstrates a good prognosis as was noted in our patient. We conclude that establishing a preoperative histopathological diagnosis is important to avoid invasive procedures.

[A CASE REPORT OF FUNGUS BALL FOUND DURING TRANSURETHRAL URETEROLITHOTOMY].

Herein we report the confirmation of fungus balls (circular collections of C.tropicalis) during a transurethral ureterolithotomy, which is as far as we know the first reported instance. A-61-year old man was referred to the urology department with bilateral ureteral calculi. Initially a transurethral ureterolithotomy was attempted but residual stones existed. During the second operation, we found numerous white fluffy material in the renal pelvis. Because of them, we were unable to have a clear field of vision to complete operation. During the third operation, we found the fungus balls again and cultured them. Cultures yielded C.tropicalis.

[GIANT BLADDER CALCULI TREATED WITH SINGLE-STAGE SIMULTANEOUS PERCUTANEOUS SUPRAPUBIC AND TRANSURETHRAL CYSTOLITHOTRIPSY: A CASE REPORT].

An 82-year-old man presented with lower abdominal pain and general malaise. Noncontrast computed tomography revealed a remarkably enlarged prostate and a full bladder with a giant stone 80 mm in diameter causing bilateral hydroureteronephrosis. Laboratory data demonstrated systemic inflammation and renal dysfunction with hyperkalemia. Acute postrenal dysfunction caused by urinary retention was diagnosed. A urethral catheter was inserted and emergent dialysis was initiated. After renal function recovered, we performed lithotripsy for the urinary bladder calculi. To achieve stone free status with a single-stage procedure, we performed simultaneous percutaneous suprapubic and transurethral cystolithotripsy. The procedure was successfully performed without significant complications.The patient was discharged 9 days after surgery, although clean intermittent catheterization was required.Giant bladder calculi are often treated with cystolithotomy because transurethral cystolithotripsy requires time to remove all fragments. In this case, we achieved stone free status in acceptable operative time by performing simultaneous percutaneous suprapubic and transurethral cystolithotripsy. In conclusion, the endourological management is an effective treatment choice, even in a case with a giant bladder calculus.