Clustering of Polymorphic Membrane Protein E Clade in Chlamydia trachomatis Lineages from Men Who Have Sex with Men.

Several Chlamydia trachomatis lineages identified through outer membrane protein A genotyping or multilocus sequence typing have been circulating worldwide among men who have sex with men. In a study in Tokyo, Japan, we demonstrate that such lineages commonly belong to a specific polymorphic membrane protein E clade across genotypes.

Better survival with lobectomy versus. sublobar resection in patients with hypermetabolic c-stage IA lung cancer on positron emission tomography/computed tomography.

OBJECTIVES: The clinical trial showed that sublobar resection was not inferior to lobectomy in terms of disease-free survival in patients with peripherally located non-small cell lung cancer ≤ 2 cm. However, it is not clear whether sublobar resection is indicated for all types of c-stage IA lung cancer. The purpose of this study was to clarify whether sublobar resection is indicated for c-stage IA hypermetabolic lung cancer. METHODS: Patients with c-stage IA lung cancer who underwent F-18 fluorodeoxyglucose positron emission tomography/computed tomography and lobectomy or sublobar resection were assessed. Of these, patients had a maximum standardized uptake value ≥ 3.0 on positron emission tomography/computed tomography were evaluated. We compared survival rates after lobectomy versus sublobar resection. Propensity score matching was performed to balance patient characteristics between groups. RESULTS: Between April 2004 and March 2023, 723 patients underwent lobectomy or sublobar resection and had a maximum standardized uptake value ≥ 3.0 on positron emission tomography/computed tomography. Lobectomy and sublobar resection were performed in 532 (73.6%) and 191 (26.4%) patients, respectively. Both the 5-year overall and disease-free survival rates were worse after sublobar resection compared with lobectomy (62.3% vs 79.9% and 53.9% vs 70.3%, respectively). After propensity score matching, the 5-year overall and disease-free survival rates remained worse after sublobar resection compared with lobectomy (60.7% vs 75.2% and 51.6% vs 67.7%, respectively). CONCLUSIONS: Patients with c-stage IA hypermetabolic lung cancer with standardized uptake value ≥ 3.0 on positron emission tomography/computed tomography had a worse prognosis after sublobar resection than after lobectomy.

The Effect of Baricitinib and Corticosteroid Compared to that of Corticosteroid Monotherapy in Severely and Critically ill Patients with COVID-19: A Japanese Multicenter Inpatient Database Study.

BACKGROUND: Systemic baricitinib and corticosteroids play important roles in treating severely and critically ill patients with coronavirus disease 2019 (COVID-19). However, the efficacy of the combination of baricitinib and corticosteroids compared to that of corticosteroid monotherapy in severely and critically ill hospitalized patients with COVID-19 remains unclear. METHODS: We analyzed severely and critically ill hospitalized patients with COVID-19 aged >18 years between January 1, 2020 and May 31, 2023, using a Japanese multicenter inpatient database. We performed propensity score matching to analyze the effect of the combination of baricitinib and corticosteroids within 2 days of hospital admission (combination group) on the 28-day and in-hospital mortality rates compared with those of corticosteroid monotherapy within 2 days of hospital admission (control group). Sensitivity analysis was performed using inverse probability weighting analysis and the generalized estimating equation method. RESULTS: The eligible patients (n=7,433) were divided into a combination (n = 679) and a control group (n = 6,754). One-to-four propensity score matching analyses included 566 combination and 2,264 control group patients. There was no significant difference in 28-day (8.5% vs. 8.8%; risk difference, -0.3% [95% confidence interval, -2.9 to 2.3]) or in-hospital (11% vs. 10%; risk difference, 1.0 [-1.9 to 3.9]) mortality rates between 2 groups. The sensitivity analysis showed similar outcomes. CONCLUSION: This observational study, using a Japanese multicenter inpatient database, found that the combination of baricitinib and corticosteroid therapy did not improve the 28-day or in-hospital mortality rates in severely and critically ill patients with COVID-19 compared to corticosteroid monotherapy.

Protocol for in vivo CRISPR screening targeting murine testicular cells.

In vivo genome-wide screening elucidates tissue-specific molecular events. Here, we present a protocol for an in vivo genome-wide CRISPR-Cas9 single-guide RNA (sgRNA) library screening technique optimized for mouse testicular cells to investigate spermatogenesis. We describe steps for virus injection, sperm sorting, and primase-based whole-genome amplification. We then detail procedures for library reconstruction using a "revival screening" technique. Our approach reveals intricate spermatogenesis processes and is adaptable for diverse tissue-specific studies. For complete details on the use and execution of this protocol, please refer to Noguchi et al.1.

Vestibular paroxysmia caused by a subarcuate artery: illustrative case.

BACKGROUND: Vestibular paroxysmia is defined by spontaneous, recurrent, short, paroxysmal episodes of vertigo. The authors present a case of vestibular paroxysmia caused by neurovascular compression of the vestibulocochlear nerve due to the subarcuate artery, which was successfully treated with microvascular decompression. OBSERVATIONS: A 46-year-old man first experienced vertigo attacks 5 years earlier. The attacks became more frequent, and left-sided tinnitus developed over the past 4 months, prompting a referral to our hospital. Carbamazepine treatment alleviated symptoms but had to be discontinued due to rash. Brain magnetic resonance imaging and angiography revealed that the left anterior inferior cerebellar artery was pressing on the cisternal segment of the left vestibulocochlear nerve. The authors diagnosed vestibular paroxysmia caused by neurovascular compression and performed microvascular decompression. During the operation, a subarcuate artery was identified as the offending vessel, with a prominent indentation on the vestibulocochlear nerve. The vertigo was completely relieved following surgery. LESSONS: Neurovascular compression of the vestibulocochlear nerve by the subarcuate artery can result in vestibular paroxysmia. https://thejns.org/doi/abs/10.3171/CASE24239.

Phospholipid scrambling induced by an ion channel/metabolite transporter complex.

Cells establish the asymmetrical distribution of phospholipids and alter their distribution by phospholipid scrambling (PLS) to adapt to environmental changes. Here, we demonstrate that a protein complex, consisting of the ion channel Tmem63b and the thiamine transporter Slc19a2, induces PLS upon calcium (Ca2+) stimulation. Through revival screening using a CRISPR sgRNA library on high PLS cells, we identify Tmem63b as a PLS-inducing factor. Ca2+ stimulation-mediated PLS is suppressed by deletion of Tmem63b, while human disease-related Tmem63b mutants induce constitutive PLS. To search for a molecular link between Ca2+ stimulation and PLS, we perform revival screening on Tmem63b-overexpressing cells, and identify Slc19a2 and the Ca2+-activated K+ channel Kcnn4 as PLS-regulating factors. Deletion of either of these genes decreases PLS activity. Biochemical screening indicates that Tmem63b and Slc19a2 form a heterodimer. These results demonstrate that a Tmem63b/Slc19a2 heterodimer induces PLS upon Ca2+ stimulation, along with Kcnn4 activation.

Genetic characteristics of invasive pneumococcal disease-derived Streptococcus pneumoniae of serogroup 24 isolated in Tokyo, Japan.

BACKGROUND: Since the introduction of the national routine vaccination program against Streptococcus pneumoniae in Japan from the early 2010s, the incidence of invasive pneumococcal disease (IPD) caused by non-vaccine serotypes has increased. This study focused on non-vaccine serogroup 24 strains derived from IPD and aimed to clarify their genetic characteristics. METHODS: Between 2013 and 2022, 121 strains identified as serogroup 24 in patients with IPD were collected and applied to multilocus sequence typing and next-generation sequencing. Whole-genome data were used to delineate phylogenetic relationships and to identify virulence and antimicrobial resistance-associated genes. RESULTS: Recent trends in sequence types (STs) were characterized by an increase in the proportion of ST162 and ST2754 for 24F and 24B, respectively, after 2018. Whole-genome phylogenetic analysis demonstrated that serogroup 24 strains were organized into three clades, closely related to STs but not with serotypes. All ST162 strains were classified as Global Pneumococcal Sequence Cluster (GPSC) 6 and harbored the virulence-associated rlrA islet, with co-trimoxazole-resistance mutations in folA and folP genes. Two ST162 strains with different serotypes 24F and 24B from the same patient were phylogenetically indistinguishable, showing that these strains were derived by serotype conversion during infection. CONCLUSION: The recent changes in predominant STs were similar to those previously reported throughout Japan, except Tokyo. Little correlation between whole-genome phylogeny and serotypes and the observed serotype conversion in one patient indicate potentially variable immunogenicity of this serogroup.

A retrospective observational study on disseminated herpes zoster in immunocompetent patients.

INTRODUCTION: Disseminated herpes zoster (DHZ) is a severe infection associated with high incidences and mortality rates in immunocompromised patients. Although studies have shown its occurrence in immunocompetent patients, its epidemiology, clinical presentation, and treatment outcomes in this cohort remain unknown. Thus, this study aimed to examine the clinical presentation, treatment, complications, and outcomes of DHZ in immunocompetent patients and compare these findings with previous studies. METHODS: We included 20 immunocompetent patients of DHZ at our institution and reviewed 42 previously published cases. We then investigated the clinical features, predisposing factors, laboratory findings, treatment, and outcomes of all cases including in-hospital mortality, neurological dysfunction at discharge, and postherpetic neuralgia. We compared DHZ-immunocompetent patients to DHZ-immunocompromised patients. RESULTS: Patients had a median age of 71.5 years and were predominantly male. The trigeminal area was the most common site of initial rash, with a mean dissemination time of 6.5 days. Pain was the most common symptom, followed by fever (approximately 40 % of cases); acyclovir was the most used treatment. Additionally, the in-hospital mortality was 0 %, neuropathy at discharge was observed in approximately 10 % of patients, and postherpetic neuralgia was present in approximately 40 % of patients. In the immunocompromised cases, the mortality rate was 12 %, which was higher than in our cases; however, the rates of neuropathy and postherpetic neuralgia were lower. CONCLUSIONS: This study provides new insights into the clinical presentation, treatment, and outcomes of DHZ cases in immunocompetent patients, highlighting its tendency for residual neurological damage despite having low mortality rates.

Supersulfide formation in the sinus mucosa of chronic rhinosinusitis.

Objectives: Disruption of the oxidative stress defense system is involved in developing various diseases. Sulfur compounds such as glutathione (GSH) and cysteine (CysSH) are representative antioxidants in the body. Recently, supersulfides, including reactive persulfide and polysulfide species, have gained attention as potent antioxidants regulating oxidative stress and redox signaling. However, their involvement in the pathogenesis of chronic rhinosinusitis (CRS) remains unclear. Methods: To clarify the changes in sulfur compounds within the sinus mucosa of each CRS subtype, we measured sulfur compound levels in the sinus mucosa of control individuals (n = 9), patients with eosinophilic CRS (ECRS) (n = 13), and those with non-ECRS (nECRS) (n = 11) who underwent sinus surgery using mass spectrometry. Results: GSH and CysSH levels were significantly reduced, and the glutathione disulfide (GSSG)/GSH ratio, an oxidative stress indicator, was increased in patients with ECRS. Despite the absence of notable variations in supersulfides, patients with ECRS and nECRS exhibited a significant reduction in glutathione trisulfide (GSSSG), which serves as the precursor for supersulfides. Conclusions: This study is the first quantitative assessment of supersulfides in normal and inflamed sinus mucosa, suggesting that sulfur compounds contribute to the pathogenesis of CRS. Level of Evidence: N/A.

Comparison of segmentectomy and wedge resection for cT1cN0M0 non-small cell lung cancer.

OBJECTIVE: Sublobar resection is considered a standard surgical procedure for early non-small cell lung cancer, although the survival of patients undergoing sublobar resection for clinical T1cN0M0 non-small cell lung cancer remains unclear. This study aimed to compare survival between segmentectomy and wedge resection for clinical T1cN0M0 non-small cell lung cancer. METHODS: This retrospective study included patients who had undergone curative surgery for cT1cN0M0 stage IA3 non-small cell lung cancer. The overall and recurrence-free survival rates of 91 patients who underwent segmentectomy or wedge resection were compared. RESULTS: Thirty-nine (42.9%) and 52 patients (57.1%) were included in the segmentectomy and wedge resection groups, respectively. The median length of follow-up was 6.0 years (95% confidence interval 4.2 - - years) (Kaplan-Meier estimate). The 5 year overall survival rates were not significantly different between the segmentectomy and wedge resection groups (67.7% vs 52.0%, P = 0.132). The 5 year recurrence-free survival rate was worse in the wedge resection group than in the segmentectomy group (66.6% vs 46.9%, P = 0.047). In univariable analysis, spread through air spaces (hazard ratio, 5.889; 95% confidence interval, 2.357-14.715; P < 0.001) was an important prognostic factor for recurrence-free survival in the wedge resection group. CONCLUSIONS: The overall survival of patients who underwent segmentectomy for clinical T1cN0M0 non-small cell lung cancer was not significantly different from that of patients who underwent wedge resection. However, patients with cT1cN0M0 non-small cell lung cancer who underwent wedge resection tended to have a worse recurrence-free survival prognosis than those who underwent segmentectomy.

Anisakid larvae in the skipjack tuna Katsuwonus pelamis captured in Japanese waters: Two-year monitoring of infection levels after the outbreak of human anisakiasis in 2018.

In 2018, human anisakiasis caused by the ingestion of the skipjack tuna Katsuwonus pelamis occurred frequently in Japan. This may be attributable to a heavy infection of A. simplex (s.s.) in the host's muscle tissue. In this study, we investigate infection levels of anisakid L3 larvae in skipjack tuna captured in Japanese waters afterward (2019-2020) to contribute to predict and prevent the outbreak of human anisakiasis. A total of 476 larvae were detected from 78 out of 85 skipjack tuna captured at 14 stations of the Pacific and East China Sea. The present parasitological survey suggests that infection levels in 2019-2020 were low, comparing that in 2018; in total only seven larvae were found from the host's muscle tissue. The collected larvae were identified by molecular methods to Anisakis berlandi, A. pegreffii, A. simplex (s.s.), A. typica and Skrjabinisakis physeteris (s.l.). Not only larvae of A. simplex (s.s.) but also those of A. berlandi were found from the muscle tissue and thus the latter species may also be a causative agent of human anisakiasis. In addition, this study confirmed the geographic distribution pattern that A. simplex (s.s.) is abundant in the Pacific, while A. pegreffii is dominant in the East China Sea. Our results contribute to understanding the risk of food poisoning and stock delimitation of host animals.

Concerted action of ataxin-2 and PABPC1-bound mRNA poly(A) tail in the formation of stress granules.

Stress induces global stabilization of the mRNA poly(A) tail (PAT) and the assembly of untranslated poly(A)-tailed mRNA into mRNPs that accumulate in stress granules (SGs). While the mechanism behind stress-induced global PAT stabilization has recently emerged, the biological significance of PAT stabilization under stress remains elusive. Here, we demonstrate that stress-induced PAT stabilization is a prerequisite for SG formation. Perturbations in PAT length impact SG formation; PAT shortening, achieved by overexpressing mRNA deadenylases, inhibits SG formation, whereas PAT lengthening, achieved by overexpressing their dominant negative mutants or downregulating deadenylases, promotes it. PABPC1, which specifically binds to the PAT, is crucial for SG formation. Complementation analyses reveal that the PABC/MLLE domain of PABPC1, responsible for binding PAM2 motif-containing proteins, plays a key role. Among them, ataxin-2 is a known SG component. A dominant-negative approach reveals that the PAM2 motif of ataxin-2 is essential for SG formation. Notably, ataxin-2 increases stress sensitivity, lowering the threshold for SG formation, probably by promoting the aggregation of PABPC1-bound mRNA. The C-terminal region is responsible for the self-aggregation of ataxin-2. These findings underscore the critical roles of mRNA PAT, PABPC1 and ataxin-2 in SG formation and provide mechanistic insights into this process.

3-Fr steerable microcatheter system via the upper limb artery in RADPLAT for right maxillary cancer.

BACKGROUND: To evaluate the efficacy of a catheter system using a 3-Fr sheath with a steerable microcatheter through right upper limb artery access for superselective intra-arterial cisplatin infusion and concomitant radiotherapy (RADPLAT) to treat right maxillary sinus squamous cell carcinoma (MS-SCC). MATERIAL AND METHODS: We retrospectively studied 46 sessions in eight patients treated between November 2020 and February 2023 using the catheter system briefly described below. A 3-Fr sheath was inserted into the distal radial, conventional radial, or brachial arteries. A coaxial catheter system with a 2.9-Fr steerable microcatheter and a 1.9-Fr microcatheter was advanced into the brachiocephalic artery. The right common carotid artery was selected by bending the tip of the steerable microcatheter. Coil embolization and intra-arterial cisplatin infusion after selecting each external carotid artery branch were achieved using this catheter system. RESULTS: Cisplatin infusion and coil embolization were successful in all sessions. Arterial occlusion at the sheath insertion sites was found in 29.4% (5/17) of the distal radial arteries and 33.3% (3/9) of the conventional radial arteries. No other major complications were observed during the procedure. CONCLUSION: Using a 3-Fr catheter system with a steerable microcatheter through right upper limb artery access is a feasible method for RADPLAT in treating right MS-SCC.

Correction: AMPK-Activated Protein Kinase Suppresses Ccr2 Expression by Inhibiting the NF-κB Pathway in RAW264.7 Macrophages.

[This corrects the article DOI: 10.1371/journal.pone.0147279.].

A Mutation in Tmem135 Causes Progressive Sensorineural Hearing Loss.

Transmembrane protein 135 (TMEM135) is a 52 kDa protein with five predicted transmembrane domains that is highly conserved across species. Previous studies have shown that TMEM135 is involved in mitochondrial dynamics, thermogenesis, and lipid metabolism in multiple tissues; however, its role in the inner ear or the auditory system is unknown. We investigated the function of TMEM135 in hearing using wild-type (WT) and Tmem135 FUN025/FUN025 ( FUN025 ) mutant mice on a CBA/CaJ background, a normal-hearing mouse strain. Although FUN025 mice displayed normal auditory brainstem response (ABR) at 1 month, we observed significantly elevated ABR thresholds at 8, 16, and 64 kHz by 3 months, which progressed to profound hearing loss by 12 months. Consistent with our auditory testing, 13-month-old FUN025 mice exhibited a severe loss of outer hair cells and spiral ganglion neurons in the cochlea. Our results using BaseScope in situ hybridization indicate that TMEM135 is expressed in the inner hair cells, outer hair cells, and supporting cells. Together, these results demonstrate that the FUN025 mutation in Tmem135 causes progressive sensorineural hearing loss, and suggest that TMEM135 is crucial for maintaining key cochlear cell types and normal sensory function in the aging cochlea.

Genome-Wide Screening Approaches for Biochemical Reactions Independent of Cell Growth.

Genome-wide screening is a potent approach for comprehensively understanding the molecular mechanisms of biological phenomena. However, despite its widespread use in the past decades across various biological targets, its application to biochemical reactions with temporal and reversible biological outputs remains a formidable challenge. To uncover the molecular machinery underlying various biochemical reactions, we have recently developed the revival screening method, which combines flow cytometry-based cell sorting with library reconstruction from collected cells. Our refinements to the traditional genome-wide screening technique have proven successful in revealing the molecular machinery of biochemical reactions of interest. In this article, we elucidate the technical basis of revival screening, focusing on its application to CRISPR-Cas9 single guide RNA (sgRNA) library screening. Finally, we also discuss the future of genome-wide screening while describing recent achievements from in vitro and in vivo screening.

Asymptomatic mature intrapericardial teratoma in an adult: a case report of a rare condition.

BACKGROUND: Benign mature teratomas are the most common type of anterior mediastinal germ cell tumor. Mature intrapericardial teratomas are generally diagnosed during infancy because of symptoms of cardiac compression. In contrast, mature adult intrapericardial teratomas are extremely rare, accounting for less than 1% of mature intrapericardial teratomas. We describe herein a case of a mature intrapericardial teratoma in an asymptomatic adult. CASE PRESENTATION: A 52-year-old woman was found by computed tomography during a health checkup to have an anterior mediastinal mass. She was asymptomatic and hemodynamically stable with no evidence of heart failure. The preoperative provisional radiological diagnosis was a mature intrapericardial teratoma. A median sternotomy revealed an approximately 5-cm diameter protruding intrapericardial mass with a smooth surface. The mass was completely resected. Histopathological examination resulted in a diagnosis of a mature intrapericardial teratoma. The patient did well and has no evidence of recurrence 5 years after surgery. CONCLUSIONS: Mature intrapericardial teratomas in adults are extremely rare. Given the risks of malignant transformation, rupture, compression of the heart, and infection, excision is indicated to prevent development of serious manifestations.

Effect of wearing masks on odor detection and recognition.

BACKGROUND: The effect of wearing masks on olfaction remains unclear. OBJECTIVES: This study aimed to clarify the differences between the effects of no masks, surgical masks, and N95 respirator masks by conducting both identification and threshold olfaction tests. METHODS: Young, healthy volunteers aged ≥ 18 years and < 30 years without awareness of apparent olfactory disorder were included. All participants filled out a questionnaire on olfaction and completed an acuity smell identification test (Open Essence test) and an olfactory threshold test (T&T olfactometry) while wearing no masks, surgical masks, or N95 respirator masks. RESULTS: In the Open Essence tests, the no-mask group score was significantly higher than those of the surgical- and N95-mask groups. Using T&T olfactometry, the median-detection threshold of the no-mask group was significantly lower than that of the surgical-mask group, and the surgical-mask group threshold was significantly lower than that of the N95-mask group. Similar patterns were observed for the median-recognition threshold. CONCLUSIONS: Wearing masks, especially an N95 mask, reduces the ability to detect and identify odors. This disadvantage should be considered by professionals such as healthcare workers, who require proper olfaction to perform appropriate tasks.

The Epidemiology of Circulating Respiratory Pathogens during the COVID-19 Pandemic.

Objective To survey the epidemiology of respiratory pathogens during the coronavirus disease 2019 (COVID-19) pandemic using multiplex polymerase chain reaction (PCR). Methods Specimens were assayed using multiplex nested PCR. Materials Specimens were obtained from outpatients who presented with symptoms of upper respiratory tract infection and asymptomatic outpatients who had contact with patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at Tohoku Medical and Pharmaceutical University Hospital in Sendai, Japan, from November 1, 2020, to May 31, 2023. The analysis included multiple specimens collected from the same patients at different time-points. Data were collected from the electronic records after testing. Results This study included 8,335 patients (4,311 men) with a median age of 59 years old, and 11,741 total specimens were collected. At least 1 positive SARS-CoV-2 result was obtained for 1,710 (14.6%) specimens. Furthermore, 15 pathogens were identified in the positive specimens, and rhinovirus/enterovirus was detected more frequently than other viruses. We identified a larger number of SARS-CoV-2-positive specimens in patients ≥10 years old. In contrast, in patients 0-9 years old, we identified a larger number of specimens positive for rhinovirus/enterovirus than for other viruses. Conclusion In this study, we examined the epidemiology of circulating respiratory pathogens during the COVID-19 pandemic era.