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Abstract Comprehensive genomic profiling (CGP) is increasingly used as a clinical laboratory test and being applied to cancer treatment; however, standardization and external quality assessments (EQA) have not been fully developed. This study performed cost-effective EQA and proficiency tests (PT) for CGP testing among multiple institutions those belong to the EQA working group of Japan Association for Clinical Laboratory Science (JACLS). This study revealed that preanalytical processes, such as derived nucleic acids (NA) extraction from formalin fixed paraffine embedded (FFPE) samples, are critical. First, EQA with extracted DNA from cell lines showed a detection rate of 100% (9 out of 9) in KRAS (c.38G > A; p.G13D), PIK3CA (p.H1047R), and B-Raf proto-oncogene, serine/threonine kinase (BRAF) (c.1799 T > A; p.V600E) in cases of > 10% variant allele frequency (VAF). However, BRAF (c.1799 T > A; p.V600E) detection decreased to 67% (6 out of 9) for a VAF of 4.9%. Second, when DNA was extracted from FFPE samples, pathogenic variants and variants with companion diagnostic indications were detected in all 10 participating laboratories. Each variant had A, and c.1799 T > A was on the other strand. In conclusion, the EQA/PT among 10 institutes with common samples revealed the importance of VAF in pre-analysis and helped us understand the significance of the pipeline and common pitfalls usually ignored by the internal quality control in a single institute.

Arterioportal fistula (APF) combined with a visceral artery pseudoaneurysm is an exceptionally rare and critical vascular disorder of the abdominal viscera, with pseudoaneurysm rupture being potentially fatal and severe APF leading to portal hypertension, both of which necessitate immediate intervention. An 87-year-old woman with a history of pancreatitis presented with upper abdomen and back pain. Laboratory tests revealed elevated amylase levels and severe anemia. A computed tomography (CT) scan showed a large dorsal pancreatic artery (DPA) pseudoaneurysm with a fistula to the main portal vein. Given her advanced age, surgery was deemed high-risk, and endovascular treatment was selected. Transcatheter arterial embolization was successfully performed using coils to embolize the DPA pseudoaneurysm. A follow-up CT 1 week postprocedure confirmed the absence of a pseudoaneurysm and no further progression of anemia.

Abstract Background Spinocerebellar ataxia type 3 (SCA3), also known as Machado–Joseph disease, is an autosomal dominant neurodegenerative disorder caused by CAG repeat expansion in exon 10 of ATXN3. Extra-cerebellar manifestations, including external ophthalmoplegia, dystonia, Parkinsonism, and peripheral neuropathy, are predominantly present in SCA3 cases. Here, we report a case of SCA3 presenting with a split hand and minipolymyoclonus. Case presentation A 73-year-old female patient presented with a 5-year history of ataxic gait. Neurological examination revealed cerebellar ataxia and minipolymyoclonus in the digits on both sides and muscle atrophy in the right hand, consistent with the split hand pattern. Electrodiagnostic studies demonstrated decreased amplitude of compound muscle action potentials and neurogenic motor unit potentials, indicating lower motor neuron involvement. Conclusions Our patient’s case indicated a split hand and minipolymyoclonus in SCA3. Clinicians should consider these extra-cerebellar manifestations in patients with SCA3. Although neither split hand nor minipolymyoclonus are likely to directly result in a specific etiological diagnosis, a common pathophysiological mechanism for both may be lower motor neuron involvement. This extracerebellar manifestation contributes to narrowing down the diagnostic possibilities for cases presenting with progressive cerebellar ataxia.

Abstract Understanding the relationship between pumice formation and long-term floatability in seawater is becoming increasingly important in terms of eruption dynamics, material cycles, biological and environmental effects, and ocean hazards. Pumice rafts were produced during the 2021 eruption of the Fukutoku-Oka-no-Ba submarine volcano in the Pacific Ocean, far from the Japanese archipelago. The pumice rafts reached the Amami-Ōshima and Okinawa Islands approximately two months after the eruption and continued to cover the sea surface at several bays and ports, providing a great opportunity to study the characteristics of raft pumices. Sieve analysis of the floating pumice indicated that the pumice rafts characteristically contained several millimeter-sized particles with a peak at 2–4 mm. This evidence raises an important question why the millimeter-sized, Fukutoku-Oka-no-Ba 2021 pumice particles were able to float for over two months, which exceeds the floatation time shown in previous studies. To answer this question, a porosity measurement technique for millimeter-to-centimeter-sized pumice particles was established and applied to drifting pumice that erupted during the Fukutoku-Oka-no-Ba 2021 eruption. The total, connected, and isolated porosities (including errors) were acquired for floating and sunken pumice particles. As studied for the floating pumice from past submarine eruptions, most floating pumice particles contain a high amount of isolated porosity (> 30 vol%) and are thus unsinkable even when the pumice size is in the millimeter scale. This study emphasizes that skeletal density is a useful measure for the determination of pumice floatability (sinkable or unsinkable). As the particle size decreases, crystals are lost from the floating pumice particles, suggesting that the particle size of the floating pumice is affected by its petrological properties (crystal content and size). A comparison with natural pumices from subaerial eruptions and experimental pumices from magma decompression experiments suggests that the Fukutoku-Oka-no-Ba 2021 pumices contain abundant isolated pores due to the suppression of expansion after fragmentation by quenching in seawater, and that the relatively low to moderate crystal content in the magma ( 30 vol%) and are thus unsinkable even when the pumice size is in the millimeter scale.

This current case report describes a Japanese woman in her 80s with xerostomia who presented with salivary gland dysfunction. She was positive for isolated anti-Ro52/SS-A antibody as determined by a chemiluminescent enzyme immunoassay and positive on a fluorescence enzyme immunoassay that recognizes both Ro52 and Ro60 antigens. A high serum concentration of anti-Ro52/SS-A antibody was determined by an enzyme-linked immunosorbent assay. A high anti-centromere antibodies (ACA) titre was also observed. Although Raynaud’s phenomenon or a high serum immunoglobulin G concentration were not observed, Masson-trichrome staining of the patient’s labial salivary glands showed considerable fibrosis. Her serum type I and type II interferon concentrations were normal. The present patient is the first with Sjögren’s syndrome (SS) to exhibit isolated anti-Ro52/SS-A antibody and ACA without anti-Ro60/SS-A antibody. This current case report presents her case together with those of four other SS patients who were positive for isolated anti-Ro52/SS-A antibody. The SS literature also includes cases positive for ACA and describes clinical characteristics. The other four SS patients with isolated anti-Ro52/SS-A antibody described here had no ACA; interstitial pneumonia and polyneuropathy were observed in these cases, although there was no consistent tendency regarding types I and II interferon.

The temporary shift from face-to-face instruction to online teaching at North American universities as an alternative solution in response to the COVID-19 pandemic brought significant challenges to international students who had to study abroad from their home countries. Studies on how international students perceive their study-abroad-from-home experiences in such an emergency remote teaching (ERT) context remain scarce. Through the lens of community of inquiry and an additional perspective of emotional presence, this study explored 13 first-year international graduate students' perceptions and experiences of their learning in ERT. Based on the analyses of the pre-learning questionnaire survey results and a series of three reflection journal entries, the study finds that teaching presence has played a vital role in shaping students' understanding and experiences when they participated in a study-abroad graduate program from their home countries. In addition, the participants demonstrated mixed emotions of both frustration and appreciation/thankfulness as well as an isolation-connectedness emotional trajectory during their learning process. The study inspires an exploration of more diverse options for international education programs and continued effort in providing institutional support to ensure better learning experiences in a post-COVID community of inquiry.

Hemophagocytic lymphohistiocytosis (HLH) has been recognized as a rare adverse event following the coronavirus disease 2019 (COVID-19) vaccination. We report a case of neuropsychiatric symptoms and refractory HLH in a woman with systemic lupus erythematosus (SLE) after receiving her COVID-19 vaccine treated with belimumab, later found to have intravascular large B-cell lymphoma (IVLBCL) at autopsy. A 61-year-old woman with SLE was referred to our hospital because of impaired consciousness and fever. One month prior to consulting, she received her second COVID-19 vaccine dose. Afterward, her consciousness level decreased, and she developed a high fever. She tested negative for SARS-CoV-2. Neuropsychiatric SLE was suspected; therefore, glucocorticoid pulse therapy was initiated on day 1 and 8. She had thrombocytopenia, increased serum ferritin levels and hemophagocytosis. The patient was diagnosed with HLH and treated with etoposide, dexamethasone and cyclosporine. Despite treatment, the patient died on day 75; autopsy report findings suggested IVLBCL as the underlying cause of HLH. Differentiating comorbid conditions remains difficult; however, in the case of an atypical clinical presentation, other causes should be considered. Therefore, we speculate that the COVID-19 vaccination and her autoimmune condition may have expedited IVLBCL development.

Respiratory syncytial virus (RSV) is a leading cause of upper and lower respiratory tract infection, especially in children and the elderly. Various vaccines containing the major transmembrane surface proteins of RSV (proteins F and G) have been tested; however, they have either afforded inadequate protection or are associated with the risk of vaccine-enhanced disease (VED). Recently, F protein-based maternal immunization and vaccines for elderly patients have shown promising results in phase III clinical trials, however, these vaccines have been administered by injection. Here, we examined the potential of using the ectodomain of small hydrophobic protein (SHe), also an RSV transmembrane surface protein, as a nasal vaccine antigen. A vaccine was formulated using our previously developed cationic cholesteryl-group-bearing pullulan nanogel as the delivery system, and SHe was linked in triplicate to pneumococcal surface protein A as a carrier protein. Nasal immunization of mice and cotton rats induced both SHe-specific serum IgG and mucosal IgA antibodies, preventing viral invasion in both the upper and lower respiratory tracts without inducing VED. Moreover, nasal immunization induced greater protective immunity against RSV in the upper respiratory tract than did systemic immunization, suggesting a critical role for mucosal RSV-specific IgA responses in viral elimination at the airway epithelium. Thus, our nasal vaccine induced effective protection against RSV infection in the airway mucosa and is therefore a promising vaccine candidate for further development.

This article is concerned with the structure of solutions to the elliptic problem for a Hénon-type equation with a forcing term: −Δu=α(x)up+κμ,inRN,u>0,inRN,(Pκ)\hspace{11.3em}-\Delta u=\alpha \left(x){u}^{p}+\kappa \mu ,\hspace{1.0em}\hspace{0.1em}\text{in}\hspace{0.1em}\hspace{0.33em}{{\mathbb{R}}}^{N},\hspace{1.0em}u\gt 0,\hspace{1.0em}\hspace{0.1em}\text{in}\hspace{0.1em}\hspace{0.33em}{{\mathbb{R}}}^{N},\hspace{13.0em}\left({{\rm{P}}}_{\kappa }) where N≥3N\ge 3, p>1p\gt 1, κ>0\kappa \gt 0, and α\alpha is a positive continuous function in RN\{0}{{\mathbb{R}}}^{N}\setminus \left\{0\right\}, and μ\mu is a nonnegative Radon measure in RN{{\mathbb{R}}}^{N}. Under suitable assumptions on the exponent pp, the coefficient α\alpha , and the forcing term μ\mu , we give a complete classification of the existence/nonexistence of solutions to problem (Pκ{{\rm{P}}}_{\kappa }) with respect to κ\kappa .

Abstract Background Pemetrexed (PEM) is the primary chemotherapy for non‐small cell lung cancer (NSCLC), showing potential for long‐term disease stability in certain cases. However, studies examining disease control with PEM therapy are lacking. This study aimed to pinpoint clinical traits in patients with NSCLC responding well to PEM therapy, predict factors influencing disease control, and suggest optimal treatment approaches. Methods A retrospective analysis of patients with NSCLC treated with PEM was performed to compare patients who achieved disease control after treatment with those who did not. Results Of 73 patients, 56 (76.7%) achieved disease control with PEM therapy. In the disease control group, a significantly higher proportion of patients exhibited good performance status (PS) and received PEM doses without reduction after the second cycle. Multivariate analysis identified bevacizumab (Bev) noncompliance, PEM dose reduction, and thyroid transcription factor‐1 (TTF‐1) negativity as significant independent risk factors for disease progression during PEM therapy. Additionally, overall survival was significantly longer in the disease control group (p

Abstract Numerous SARS-CoV-2 variant strains with altered characteristics have emerged since the onset of the COVID-19 pandemic. Remdesivir (RDV), a ribonucleotide analogue inhibitor of viral RNA polymerase, has become a valuable therapeutic agent. However, immunosuppressed hosts may respond inadequately to RDV and develop chronic persistent infections. A patient with respiratory failure caused by interstitial pneumonia, who had undergone transplantation of the left lung, developed COVID-19 caused by Omicron BA.5 strain with persistent chronic viral shedding, showing viral fusogenicity. Genome-wide sequencing analyses revealed the occurrence of several viral mutations after RDV treatment, followed by dynamic changes in the viral populations. The C799F mutation in nsp12 was found to play a pivotal role in conferring RDV resistance, preventing RDV-triphosphate from entering the active site of RNA-dependent RNA polymerase. The occurrence of diverse mutations is a characteristic of SARS-CoV-2, which mutates frequently. Herein, we describe the clinical case of an immunosuppressed host in whom inadequate treatment resulted in highly diverse SARS-CoV-2 mutations that threatened the patient’s health due to the development of drug-resistant variants.

PurposeA short period of disuse of 1–2 weeks due to factors such as illness or injury can lead to muscle atrophy, affecting both athletic performance and health. Recent research has shown that uridine 5′-monophosphate (5′-UMP) can counteract disuse-induced muscle atrophy by increasing PGC-1α expression and inhibiting atrogin-1 expression. However, the effect of 5′-UMP on disuse muscle atrophy in humans remains unknown. Therefore, the aimed of this study was to explore the effects of 5′-UMP supplementation during detraining on short-term disuse muscle atrophy in healthy men.MethodsFollowing a 6-week resistance training program on upper arm, healthy men were randomized to either a UMP group (n = 11) or a placebo group (n = 10), taking their respective supplements during the 2-week detraining period. Muscle thickness, an indicator of muscle hypertrophy and atrophy, was measured at 3 positions (MT50, MT60, and MT70) at baseline, 1 week, and 2 weeks after detraining.ResultsBoth groups showed a significant decrease in muscle thickness at MT70. The relative decrease was greater in the placebo group (2.4 ± 2.8%) than in the UMP group (0.0 ± 2.0%), significantly (p = 0.034) at 1 week. However, no significant difference was observed at MT50 and MT60.ConclusionAfter the hypertrophy, 5′-UMP may prevent muscle atrophy due to the detraining within the first week.