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Background: Although faecal DNA testing of Fusobacterium nucleatum ( Fn) is expected to be useful for colorectal neoplasia detection, there is no standardized quantification method of Fn. We performed this study to establish a possible standardized method. Methods: In this study, 322 participants including 71 subjects without colorectal neoplasia (control group), 31 patients with non-advanced colorectal adenoma, 93 patients with advanced colorectal adenoma, and 127 patients with colorectal cancer were enrolled. Faecal Fn were quantified by droplet digital PCR (ddPCR) using two PCR primer-probe sets reported previously that are tentatively named Fn1 and Fn2. Fn1 has been used in ddPCR by us and Fn2 has been widely used in quantitative real-time PCR. Results: The Fn copy number using Fn1 was five times higher than that using Fn2, with a linear relationship shown between them. Receiver operating characteristic curve analysis showed the area under the curve (AUC) to be almost the same between Fn1 and Fn2 in discriminating between the control group and the colorectal cancer group (AUC = 0.81 and 0.81, respectively), and between the control/non-advanced colorectal adenoma group and the advanced colorectal adenoma/colorectal cancer group (AUC = 0.74 and 0.74, respectively). Conclusions: As the diagnostic performance was quite similar between Fn1 and Fn2, ddPCR-based Fn testing using Fn1 and Fn2 could be a possible standardized method for a colorectal neoplasia screening test, considering that Fn levels quantified by Fn1 are about five times higher than those by Fn2.

Intermittent administration of L-dopa in Parkinson's disease is associated with L-dopa-induced dyskinesia (LID). Long-acting dopamine agonists may reduce the risk of LID by continuous dopaminergic stimulation. We examined the LID-like behavior, preprodynorphin messenger ribonucleic acid (mRNA) expression in the striatum (a neurochemical LID hallmark), and the volume of the entopeduncular nucleus (a pathological LID hallmark) in Parkinson's disease rat models that were treated with L-dopa and cabergoline. Cabergoline co-treatment with L-dopa reduced LID, striatal preprodynorphin mRNA expression, and hypertrophy of the entopeduncular nucleus, indicating that cabergoline has an anti-LID effect independent of the L-dopa-sparing effect.

Transactivation response DNA-binding protein 43 (TDP-43)-immunoreactive neuronal cytoplasmic inclusions (NCIs) are the histopathological hallmarks of amyotrophic lateral sclerosis (ALS). They are classified as skein-like inclusions, round inclusions, dot-like inclusions, linear wisps, and diffuse punctate cytoplasmic staining (DPCS). We hypothesized that TDP-43-immunoreactive DPCS may form the early-stage pathology of ALS. Hence, we investigated phosphorylated TDP-43 pathology in the upper and lower motor neurons of patients with ALS and control participants. We designated patients whose disease duration was ≤1 year as short-duration ALS (n = 7) and those whose duration equaled 3–5 years as standard-duration ALS (n = 6). DPCS and skein-like inclusions were the most common NCIs in short-duration and standard-duration ALS, respectively. The density of DPCS was significantly higher in short-duration ALS than that in standard-duration ALS and was inversely correlated with disease duration. DPCS was not ubiquitinated and disappeared after proteinase K treatment, suggesting that it was not aggregated. Immunoelectron microscopy revealed that DPCS corresponded to nonfibrillar TDP-43 localized to the ribosomes of the rough endoplasmic reticulum (ER). These findings suggest that nonfibrillar TDP-43 accumulation in the rough ER is the earliest TDP-43 pathology in ALS, which may be helpful in developing future TDP-43 breakdown strategies for ALS.

Introduction: We previously developed a novel methylation assay, the combined restriction digital PCR (CORD) assay, consisting of treatment of DNA with methylation-sensitive restriction enzymes and droplet digital PCR. Methods: In this study, we assessed the diagnostic performance of serum methylated Homeobox A1 (mHOXA1) and methylated somatostatin (mSST) using the CORD assay in combination with CA19-9 for pancreatic cancer using serum samples from 82 healthy individuals, 13 patients with benign pancreatic disease, 3 patients with branched-duct intraductal papillary mucinous neoplasm, and 91 patients with pancreatic cancer. Results: For the single marker tests, sensitivity for all stages of pancreatic cancer, stage I cancer, and specificity were, respectively, 71.4%, 50.0%, and 94.9% for CA19-9; 51.6%, 68.8%, and 90.8% for mHOXA1; and 50.1%, 68.8%, and 94.9% for mSST. Those for the combined marker tests were, respectively, 86.8%, 81.3%, and 85.7% for combined mHOXA1 and CA19-9; 86.8%, 87.5%, and 89.8% for combined mSST and CA19-9; and 89.0%, 87.5%, and 85.7% for all three markers combined. Conclusion: The combination of mHOXA1 and mSST with CA19-9 appears to be useful to detect pancreatic cancer even at an early stage.

Mild palmar digital neuropathy may be underestimated because selective nerve conduction studies (NCS) of the palmar digital nerve are challenging. We herein report two cases of palmar digital neuropathy. We performed sensory NCS in each finger using the standard approach. Both cases showed a decrease in the amplitude of sensory nerve action potential (SNAP) in the localized finger. Furthermore, the sensory nerve inching test identified the lesion site. When performing NCS in patients with finger sensory impairment, we recommend recording the SNAP in each finger using standard NCS at the wrist, as well as sensory nerve inching testing.

Background: Although serum carbohydrate antigen 19-9 (CA19-9) is widely used as a useful biomarker of pancreatic cancer for monitoring the response to therapy, it is not recommended for screening of early pancreatic cancer because of its limited sensitivity for small tumors. Thus, it is critical to discover novel serum biomarkers to complement CA19-9 in order to improve sensitivity. Although methylated runt-related transcription factor 3 (RUNX3) is a biomarker of pancreatic cancer, its detection by conventional bisulfite-based methylation assays from a small serum sample amount is very difficult. Therefore, we developed a new methylation assay, the combined restriction digital PCR (CORD) assay, that enables counting of even one copy of a methylated gene in a small DNA sample amount without DNA bisulfite treatment. Objectives: We evaluated the sensitivity and specificity of serum DNA testing of methylated RUNX3 by the CORD assay in combination with and without CA19-9 for the detection of pancreatic cancer in 55 patients with pancreatic cancer, 12 patients with benign pancreatic disease, and 80 healthy individuals. Results: The CORD assay of methylated RUNX3 had a sensitivity of 50.9% (28/55) and specificity of 93.5% (86/92). Combination of the CORD assay of methylated RUNX3 and CA19-9 resulted in a sensitivity of 85.5% (47/55) and specificity of 93.5% (86/92) for all stages of pancreatic cancer and a sensitivity of 77.8% (7/9) for stage I pancreatic cancer. Conclusions: ombination of the CORD assay and CA19-9 may provide an alternative screening strategy for detecting early-stage pancreatic cancer.

Small-fiber neuropathies are a heterogeneous group of disorders affecting thinly myelinated Aδ and unmyelinated C fibers. Patients generally present with neuropathic pain, while dysesthesia, allodynia, pain, burning sensations, and cold sensations are frequently present in a length-dependent pattern. Additional autonomic features of the gastrointestinal, urinary, or cardiovascular systems are frequently observed. Deep-tendon reflexes and nerve conduction tests yield normal results. Skin biopsy is useful for the diagnosis, and can demonstrate the loss of intraepidermal nerve fibers in small-fiber neuropathy and has a diagnostic sensitivity of 80%. Although many causes of small-fiber neuropathy have been reported, the cause remains unknown in 30-50% of the cases. Treatment is directed at the underlying etiology and is supported with symptomatic treatment.

This study presents the results of the ERTDF S-12 project for searching an optimum reduction scenario of the short-lived climate pollutants (SLCPs) to simultaneously mitigate the global warming and environmental problems. The study utilized REAS emission inventory, Asia-Pacific Integrated Model-Enduse (AIM/Enduse), MIROC6 climate model, NICAM non-hydrostatic atmospheric model, and models for estimating environmental damages to health, agriculture, and flood risks. Results of various scenario search indicate that it is difficult to attain simultaneous reduction of global warming and environmental damages, unless a significant reduction of CO2 is combined with carefully designed SLCP reductions for CH4, SO2, black carbon (BC), NOx, CO, and VOCs. In this scenario design, it is important to take into account the impact of small BC reduction to the surface air temperature and complex atmospheric chemical interactions such as negative feedback between CH4 and NOx reduction. We identified two scenarios, i.e., B2a and B1c scenarios which combine the 2D-scenario with SLCP mitigation measures using End-of-Pipe (EoP) and new mitigation technologies, as promising to simultaneously mitigate the temperature rise by about 0.33 °C by 2050 and air pollution in most of the globe for reducing damages in health, agriculture, and flood risk. In Asia and other heavy air pollution areas, health-care measures have to be enhanced in order to suppress the mortality increase due to high temperature in hot spot areas caused by a significant cut of particulate matter. For this situation, the B1b scenario is better to reduce hot spot areas and high-temperature damage to the public health.

Background A previous comparative study in Japan has demonstrated that the two consecutive UroVysion tests are useful tools to detect the presence of bladder cancer during follow-up after transurethral resection, but they also presented their high rates of false-positive results. Here, we aimed to evaluate the relationship between the UroVysion tests and subsequent intravesical recurrence. Methods In the previous study, patients without bladder cancer during the first analysis showed the same examination set repeated 3 months later as the second analysis. In this follow-up study, 326 patients showed negative findings confirmed on cystoscopy during the second UroVysion test. Recurrence-free survival was assessed using a median follow-up of 27 months. Results In the two consecutive UroVysion tests, 214 patients (65.6%) showed negative UroVysion results in both tests, whereas 91 presented a positive result on either tests and 21 patients presented positive results in both tests. During the follow-up, 40 patients (12.3%) had an intravesical recurrence with non-muscle-invasive bladder cancer. The recurrence rates in patients with negative results in both tests, those with one positive result in either tests, and those with positive results in both tests were 8.4%, 16.5%, and 33.3%, respectively. The multivariate analysis indicated that the history of bladder cancer and the consecutive UroVysion test pattern were independent risk factors for recurrence. Conclusions Our data confirmed the effectiveness of two consecutive UroVysion tests in predicting intravesical recurrence after TURBT. Further prospective studies would help determine an appropriate interval for cystoscopy follow-up.

Liquid biopsies are not used in practice for hepatocellular carcinoma (HCC). Epi proColon is the first commercial blood‐based test for colorectal cancer screening based on methylated DNA testing of the septin 9 gene (SEPT9). However, Epi proColon has some disadvantages, including the requirement of a large amount of blood and lack of quantitative performance. Therefore, we previously developed a novel liquid biopsy test that can quantitatively detect even a single copy of methylated SEPT9 in a small amount of DNA. In the current study, we evaluated the application potential of this assay for diagnosing HCC. Study subjects included 80 healthy volunteers, 45 patients with chronic liver disease (CLD) without HCC, and 136 patients with HCC (stage 0, 12; stage A, 50; stage B, 31; stage C, 41; and stage D, 2), according to the Barcelona Clinic Liver Cancer staging system. For the assay, DNA was treated with methylation‐sensitive restriction enzymes in two steps, followed by multiplex droplet digital polymerase chain reaction. The median copy number of methylated SEPT9 was 0.0, 2.0, and 6.4 in the healthy control, CLD, and HCC groups, respectively, with significant differences among the groups (HCC vs. healthy control, P

We synthesized phenylacetylenes containing β-lactoside, β-cellobioside, or β-maltoside, and polymerized them to produce the corresponding poly (phenylacetylene)s. In these poly (phenylacetylene)s, the pendent carbohydrates were tethered to the mainchains by serinol spacers. Because similar glycosyl serinol units are found in the natural glycosphingolipids in cell membranes, the densely packed carbohydrate clusters along the poly (phenylacetylene) mainchains act as molecular mimics of cell surface glycoclusters. We analyzed the conformation of the glycosylated poly (phenylacetylene)s using circular dichroism spectroscopy, and found that the spatial carbohydrate packing within the glycoclusters changed on the addition of salts.

Primary central nervous system vasculitis (PCNSV) is an uncommon vasculitis restricted to the small- and medium-sized vessels in the brain and spinal cord. Previously, only 9 cases have been reported that initially manifested as an isolated spinal cord lesion with subsequent brain involvement, where the longest interval from the onset to brain involvement was 1 year and 11 months. We herein report the case of an isolated spinal cord lesion with subsequent brain involvement appearing seven years and five months later. This case shows that brain lesions can develop after an extended interval from spinal onset in PCNSV.

A 72-year-old man presented with continuous hyperCKemia and intermittent claudication. He exhibited no calf muscle hypertrophy at that time or afterward. Other than an increased creatine kinase (CK) level (1,525 U/l), none of the laboratory tests was abnormal, including that for myositis-related autoantibodies. Electromyography showed neurogenic changes in the left gastrocnemius. Lumbar magnetic resonance imaging revealed spinal canal stenosis (L3/4, L4/5), left L4 radiculopathy, and bilateral S1 radiculopathy. T2-weighted and short tau inversion recovery images showed high signal intensity in the bilateral biceps femoris and gastrocnemius. Histopathological evaluation of a specimen obtained from the right gastrocnemius muscle revealed neurogenic changes. The patient was diagnosed with S1 radiculopathy caused by lumbar spinal canal stenosis with hyperCKemia. Although S1 radiculopathy with hyperCKemia is usually associated with calf muscle hypertrophy, we should consider S1 radiculopathy in patients with intermittent claudication and hyperCKemia even in the absence of calf muscle hypertrophy.

BackgroundIt remains unclear why patients with young-onset Parkinson’s disease more often develop levo-dihydroxyphenylalanine (L-dopa)-induced dyskinesia (LID) and have a more severe form than patients with old-onset Parkinson’s disease. Previous studies using animal models have failed to show young-onset Parkinson’s disease enhances LID.ObjectivesTo evaluate the association of age at dopaminergic denervation (onset age) and initiation of L-dopa treatment (treatment age) with LID development in model rats.MethodsWe established rat models of young- and old-lesioned Parkinson’s disease (6-hydroxydopamine lesions at 10 and 88 weeks of age, respectively). Dopaminergic denervation was confirmed by the rotational behavior test using apomorphine. Rats in the young-lesioned group were allocated to either L-dopa treatment at a young or old age, or saline treatment. Rats in the old-lesioned group were allocated to either L-dopa treatment or saline group. We evaluated L-dopa-induced abnormal involuntary movements during the 14-day treatment period. We also examined preprodynorphin mRNA expression in the striatum (a neurochemical hallmark of LID) and the volume of the medial globus pallidus (a pathological hallmark of LID).ResultsLID-like behavior was enhanced in L-dopa-treated young-lesioned rats compared with L-dopa-treated old-lesioned rats. Preprodynorphin mRNA expression was higher in L-dopa-treated young-lesioned rats than in in L-dopa-treated old-lesioned rats. The volume of the medial globus pallidus was greater in L-dopa-treated young-lesioned rats than in L-dopa-treated old-lesioned rats. Treatment age did not affect LID-like behavior or the degree of medial globus pallidus hypertrophy in the young-lesioned model.ConclusionBoth dopaminergic denervation and L-dopa initiation at a young age contributed to the development of LID; however, the former may be a more important factor.

Tumor necrosis factor-alpha (TNF-α) inhibitors are increasingly used for various autoimmune diseases. Demyelinating events in the CNS, including myelitis, are reportedly associated with TNF-α inhibitor exposure. Behcet's disease rarely involves the spinal cord. A 51-year-old Japanese woman presented with back pain, leg weakness, and numbness during golimumab administration, a TNF-α inhibitor, for Behcet's disease. Magnetic resonance imaging revealed multifocal myelitis in the cervical and thoracic spinal cords. Discontinuation of golimumab and steroid therapy were effective and the symptoms have not relapsed. Although it is possible that the patient's myelitis was part of the symptoms of neuro-Behcet's disease, we believe that golimumab likely played a role in the myelitis development.

The aim of this systematic review was to assess the best available evidence on semi-solid nutrients for prevention of complications associated with enteral tube feeding (ETF). PubMed (MEDLINE), EMBASE, Cochrane Central Register of Controlled Trial, Ichushi-web, and World Health Organization International Clinical Trials Registry Platform databases were searched for relevant articles. Randomized controlled trials (RCTs), cluster RCTs, and crossover trials comparing the effects of semi-solid nutrients with those of control interventions in patients on ETF were included in the review. The primary outcome was development of gastroesophageal reflux (GER). Eight RCTs and five crossover trials involving 889 study participants in total were examined via meta-analysis. The meta-analysis showed that semi-solid nutrients significantly decreased the risk of GER (risk ratio 0.39; 95% confidence interval (CI) 0.21 to 0.73) and the GER index (mean difference −2.93; 95% CI −5.18 to −0.68). Dwell time in the stomach was significantly shortened (standardized mean difference (SMD) −0.50; 95% CI −0.99 to −0.02), as was care time defined as the time needed to prepare and administer the nutrient solution (SMD −8.02; 95% CI −10.94 to −5.10). Semi-solid nutrients significantly decrease the risk of GER and the dwell time in the stomach in adult patients.

This study aimed to evaluate genotype-phenotype correlations of Parkinson’s disease (PD) patients with phospholipase A2 group V (PLA2G6) variants. We analyzed the DNA of 798 patients with PD, including 78 PD patients reported previously, and 336 in-house controls. We screened the exons and exon-intron boundaries of PLA2G6 using the Ion Torrent system and Sanger method. We identified 21 patients with 18 rare variants, such that 1, 9, and 11 patients were homozygous, heterozygous, and compound heterozygous, respectively, with respect to PLA2G6 variants. The allele frequency was approximately equal between patients with familial PD and those with sporadic PD. The PLA2G6 variants detected frequently were identified in the early-onset sporadic PD group. Patients who were homozygous for a variant showed more severe symptoms than those who were heterozygous for the variant. The most common variant was p.R635Q in our cohort, which was considered a risk variant for PD. Thus, the variants of PLA2G6 may play a role in familial PD and early-onset sporadic PD.

The main modalities for gastric cancer screening are limited to upper gastrointestinal endoscopy and contrast radiography. The former is invasive, and the latter has high false-negative rates. Thus, alternative diagnostic strategies are required. One solution may be a liquid biopsy. Methylated RUNX3 is a well-known biomarker of gastric cancer but it is very difficult to detect with conventional bisulfite-based methylation assays when only a small amount of serum is available. We developed the combined restriction digital PCR (CORD) assay, a new methylation assay allowing for the counting of as little as one copy of a methylated gene in a small sample of DNA without necessitating DNA bisulfite treatment. We evaluated the sensitivity and specificity of the serum DNA testing of methylated RUNX3 by the CORD assay for the detection of early gastric cancer using 50 patients with early gastric cancer and 61 control individuals. The CORD assay had a sensitivity of 50.0% and a specificity of 80.3% for early gastric cancer. Methylated RUNX3 copies were significantly associated with tumor size, massive submucosal invasion, and lymph-vascular invasion. After the treatment, the median number of methylated RUNX3 copies was significantly decreased. The CORD assay may provide an alternative screening strategy to detect even early-stage gastric cancer.

Autoantibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been detected in inflammatory demyelinating central nervous system diseases. A 30-year-old woman had blurred vision, marked optic nerve disc swelling, serous retinal detachment at the macular on optic coherence tomography, and MOG-IgG seropositivity. The patient was thought to have optic papillitis associated with MOG-IgG. Her symptoms rapidly improved after high-dose methylprednisolone therapy. We hypothesize that serous retinal detachment was secondary, arising from optic papillitis. This is the first report of the concurrence of optic papillitis with MOG-IgG and serous retinal detachment. MOG-IgG should be tested in patients with marked optic disc swelling.

Background Hyperthermia in patients with acute ischemic stroke is associated with poor outcome. Although previous studies have shown a negative effect on functional outcome, even in patients treated with intravenous recombinant tissue plasminogen activator (rt-PA), the effect on survival remains unclear. Aims of the study The aim of this study was to evaluate the association between the functional and survival prognosis and hyperthermia in patients with acute ischemic stroke treated with rt-PA. Methods We studied 120 patients treated with rt-PA from 2306 consecutive Japanese patients with acute cerebral infarction at Aomori Prefectural Central Hospital between December 2009 and March 2017. We defined hyperthermia as ≥38°C within 72 hours after rt-PA administration. Propensity score matching was used to compare 34 non-hyperthermia and hyperthermia patient pairs. Results Final modified Rankin Scale scores were higher in the hyperthermia group than in the non-hyperthermia group. In addition, the Kaplan-Meier model showed that the non-hyperthermia group had significantly better survival rates than the hyperthermia group (hazard ratio, 5.3; 95% confidence intervals, 1.2-24.8). Conclusions Hyperthermia within 3 days after rt-PA is associated with poor functional prognosis and survival outcome in patients with acute cerebral infarction.

Although methylated TWIST1 is a biomarker of colorectal neoplasia, its detection from serum samples is very difficult by conventional bisulfite-based methylation assays. Therefore, we have developed a new methylation assay that enables counting of even one copy of a methylated gene in a small DNA sample amount without DNA bisulfite treatment. We performed this study to evaluate the sensitivity and specificity of serum DNA testing by the new methylation assay in combination with and without the fecal immunochemical test for hemoglobin for the detection of colorectal neoplasia. This study comprised 113 patients with colorectal neoplasia and 25 control individuals. For the new methylation assay, DNA was treated in two stages with methylation-sensitive restriction enzymes, followed by measurement of copy numbers of hTERT and methylated TWIST1 by multiplex droplet digital PCR. The fecal immunochemical test had a sensitivity of 8.0% for non-advanced adenoma, 24.3% for advanced adenoma, and 44.4% for colorectal cancer, and a specificity of 88.0%. The new assay had a sensitivity of 36.0% for non-advanced adenoma, 30.0% for advanced adenoma, and 44.4% for colorectal cancer, and a specificity of 92.0%. Combination of the both tests increased the sensitivity to 40.0%, 45.7%, and 72.2% for the detection of non-advanced adenoma, advanced adenoma, and colorectal cancer, respectively, and resulted in a specificity of 84.0%. Combination of both tests may provide an alternative screening strategy for colorectal neoplasia including potentially precancerous lesions and colorectal cancer.

The purpose of this study is to prepare a nursing protocol for preventing discontinuation of treatments using a method other than physical restraint during acute exacerbation of chronic heart failure in patients with impaired cognitive function. For the first stage of the study, we prepared a draft of the nursing protocol based on a basic survey. For the second stage, semi-structured interviews were conducted with 5 nurses specialized in chronic heart failure and 10 nurses in dementia case to ensure content validity of the draft protocol. For the third stage, we examined the possibility of clinical application of the revised version of the protocol draft prepared in the second stage of the study. For assessment items, significant points of nursing care, and specific nursing care practice in this revised version, 154 subjects (93.9%) considered effective for patients, in terms of prevention of treatment discontinuation using a method other than physical restraint. All items and contents were considered useful by more than 60% of the nurses. Considering that the nurses working in the clinical setting reported 93.9% of usefulness, we concluded that this nursing protocol remained valid at a certain level. We also received a comment from the certified nurses that we should include the basic contents for newly graduated nurses. We consider that this nursing protocol will be also useful for newly graduated nurses to acquire knowledge. It helped to standardize nursing care in order to predict potential risks for patients with impaired cognitive function.

• Serotonin and norepinephrine transporters are capable of dopamine reuptake in the parkinsonian striatum.

A 72-year-old woman presented with a 6-week history of gait disturbance and mild disturbance of consciousness. For 9 months, she had been treated for advanced non-small cell lung cancer with atezolizumab. MRI revealed symmetrical high signal in the thalamus bilaterally (figure). She did not have evidence of cancer recurrence or metastases. Serum autoimmune antibodies were absent (anti-AQP4, anti-MOG, anti-amphiphysin, CV2, PNMA2 [Ma2/Ta], Ri, Yo, Hu, recoverin, SOX1, titin, zic4, GAD65, and Tr [DNER]). In the CSF, she had high immunoglobulin G index and positive oligoclonal bands but normal myelin basic protein, absent anti-NMDA receptor and anti-MOG antibodies, and no evidence of infection. Cytology was normal. She was diagnosed with autoimmune encephalitis associated with atezolizumab treatment and treated with steroids and IV immunoglobulin 9 weeks after the onset of symptoms. The size of the lesions decreased after immunotherapy started, but she remained bedridden.

Liquid biopsies are not used in practice for hepatocellular carcinoma (HCC). Epi proColon is the first commercial blood‐based test for colorectal cancer screening based on methylated DNA testing of the septin 9 gene (SEPT9). However, Epi proColon has some disadvantages, including the requirement of a large amount of blood and lack of quantitative performance. Therefore, we previously developed a novel liquid biopsy test that can quantitatively detect even a single copy of methylated SEPT9 in a small amount of DNA. In the current study, we evaluated the application potential of this assay for diagnosing HCC. Study subjects included 80 healthy volunteers, 45 patients with chronic liver disease (CLD) without HCC, and 136 patients with HCC (stage 0, 12; stage A, 50; stage B, 31; stage C, 41; and stage D, 2), according to the Barcelona Clinic Liver Cancer staging system. For the assay, DNA was treated with methylation‐sensitive restriction enzymes in two steps, followed by multiplex droplet digital polymerase chain reaction. The median copy number of methylated SEPT9 was 0.0, 2.0, and 6.4 in the healthy control, CLD, and HCC groups, respectively, with significant differences among the groups (HCC vs. healthy control, P, We showed that a novel liquid biopsy test targeting methylated SEPT9 is useful for diagnosing HCC.

Objectives: Physician-staffed helicopter transport is faster than ground transport and allows for prompt medical care of patients in rural areas. In this study, we evaluated the relationship between helicopter transport and the prognosis of patients with acute cerebral infarction in rural Japan. Methods: This retrospective, observational study included 546 patients with acute cerebral infarction attending Aomori Prefectural Central Hospital, which serves a rural region of Japan. Patients were separated into 2 transport groups: physician-staffed helicopter emergency medical services and ground emergency medical services. Patients were assessed for stroke severity, treatment, and prognosis. Results: Of the 546 patients, 11.2% were transported by physician-staffed helicopter emergency medical services and 88.8% by ground emergency medical services. Although the distance transported was significantly longer in the physician-staffed helicopter emergency medical services group, the time from onset to reaching our hospital was similar between the groups. National Institutes of Health Stroke Scale on admission and final prognosis were significantly worse with physician-staffed helicopter emergency medical services than with ground emergency medical services. Multivariate analysis showed no association between transport system and prognosis. Conclusions: In this study, patients transported by physician-staffed helicopter emergency medical services had more severe stroke symptoms and poorer functional outcomes than those transported by ground emergency medical services. However, the transport time was shorter for physician-staffed helicopter emergency medical services; thus, physician-staffed helicopter emergency medical services may be useful for reducing transport time for patients in rural Japan.