Estimating the time-varying reproduction number of COVID-19 with a state-space method.

After slowing down the spread of the novel coronavirus COVID-19, many countries have started to relax their confinement measures in the face of critical damage to socioeconomic structures. At this stage, it is desirable to monitor the degree to which political measures or social affairs have exerted influence on the spread of disease. Though it is difficult to trace back individual transmission of infections whose incubation periods are long and highly variable, estimating the average spreading rate is possible if a proper mathematical model can be devised to analyze daily event-occurrences. To render an accurate assessment, we have devised a state-space method for fitting a discrete-time variant of the Hawkes process to a given dataset of daily confirmed cases. The proposed method detects changes occurring in each country and assesses the impact of social events in terms of the temporally varying reproduction number, which corresponds to the average number of cases directly caused by a single infected case. Moreover, the proposed method can be used to predict the possible consequences of alternative political measures. This information can serve as a reference for behavioral guidelines that should be adopted according to the varying risk of infection.

Oncologic outcomes in elderly patients who underwent hysterectomy for endometrial cancer: a multi-institutional survey in Kinki District, Japan.

BACKGROUND: The goal of this study is to assess the oncologic outcomes of elderly patients who underwent hysterectomy for endometrial cancer across three variables: hysterectomy approach, lymph node resection, and adjuvant therapy. METHODS: Hospital records of patients aged ≥ 70 years who underwent hysterectomy for endometrial cancer were obtained from 19 institutions. Patients were categorized into three risk groups: low, intermediate, and high. In each group, disease-free survival and overall survival were compared according to hysterectomy approach, lymph node resection, and adjuvant therapy using Kaplan-Meier method. Cox regression analysis with a 95% confidence interval was performed to estimate relative risk (RR) of death. RESULTS: A total of 1246 patients were included. In the low-risk group, the adjusted RR for death for minimally invasive surgery (MIS) versus laparotomy and lymph node resection versus no lymph node resection were 0.64 (0.24-1.72) and 0.52 (0.24-1.12), respectively. In the intermediate-risk group, the adjusted RR for death for MIS versus laparotomy, lymph node resection versus no lymph node resection, and adjuvant therapy versus no adjuvant therapy were 0.80 (0.36-1.77), 0.60 (0.37-0.98), and 0.89 (0.55-1.46), respectively. In the high-risk group, the adjusted RRs for death for lymph node resection versus no lymph node resection and adjuvant therapy versus no adjuvant therapy were 0.56 (0.37-0.86) and 0.60 (0.38-0.96), respectively. CONCLUSIONS: MIS is not inferior to laparotomy in uterine-confined diseases. Lymph node resection improved the outcome for all disease stages and histological types. In contrast, adjuvant therapy improved the outcomes only in high-risk patients.

Statistical inference of the rate of RNA polymerase II elongation by total RNA sequencing.

MOTIVATION: Sequencing total RNA without poly-A selection enables us to obtain a transcriptomic profile of nascent RNAs undergoing transcription with co-transcriptional splicing. In general, the RNA-seq reads exhibit a sawtooth pattern in a gene, which is characterized by a monotonically decreasing gradient across introns in the 5'-3' direction, and by substantially higher levels of RNA-seq reads present in exonic regions. Such patterns result from the process of underlying transcription elongation by RNA polymerase II, which traverses the DNA strand in a 5'-3' direction as it performs a complex series of mRNA synthesis and processing. Therefore, data of sequenced total RNAs could be utilized to infer the rate of transcription elongation by solving the inverse problem. RESULTS: Though solving the inverse problem in total RNA-seq has the great potential, statistical methods have not yet been fully developed. We demonstrate what extent the newly developed method can be useful. The objective is to reconstruct the spatial distribution of transcription elongation rates in a gene from a given noisy, sawtooth-like profile. It is necessary to recover the signal source of the elongation rates separately from several types of nuisance factors, such as unobserved modes of co-transcriptionally occurring mRNA splicing, which exert significant influences on the sawtooth shape. The present method was tested using published total RNA-seq data derived from mouse embryonic stem cells. We investigated the spatial characteristics of the estimated elongation rates, focusing especially on the relation to promoter-proximal pausing of RNA polymerase II, nucleosome occupancy and histone modification patterns. AVAILABILITY AND IMPLEMENTATION: A C implementation of PolSter and sample data are available at https://github.com/yoshida-lab/PolSter. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Length of myelin internodes of individual oligodendrocytes is controlled by microenvironment influenced by normal and input-deprived axonal activities in sensory deprived mouse models.

Oligodendrocytes myelinate neuronal axons to increase conduction velocity in the vertebrate central nervous system (CNS). Recent studies revealed that myelin formed on highly active axons is more stable compared to activity-silenced axons, and length of the myelin sheath is longer in active axons as well in the zebrafish larva. However, it is unclear whether oligodendrocytes preferentially myelinate active axons compared to sensory input-deprived axons in the adult mammalian CNS. It is also unknown if a single oligodendrocyte forms both longer myelin sheaths on active axons and shorter sheaths on input-deprived axons after long-term sensory deprivation. To address these questions, we applied simultaneous labeling of both neuronal axons and oligodendrocytes to mouse models of long-term monocular eyelid suturing and unilateral whisker removal. We found that individual oligodendrocytes evenly myelinated normal and input-deprived axons in the adult mouse CNS, and myelin sheath length on normal axons and input-deprived axons formed by a single oligodendrocyte were comparable. Importantly, the average length of the myelin sheath formed by individual oligodendrocytes did change depending on relative abundance of normal against sensory-input deprived axons, indicating an abundance of deprived axons near an oligodendrocyte impacts on myelination program by a single oligodendrocyte.

Rabies virus-mediated oligodendrocyte labeling reveals a single oligodendrocyte myelinates axons from distinct brain regions.

Oligodendrocytes myelinate neuronal axons during development and increase conduction velocity of neuronal impulses in the central nervous system. Neuronal axons extend from multiple brain regions and pass through the white matter; however, whether oligodendrocytes ensheath a particular set of axons or do so randomly within the mammalian brain remains unclear. We developed a novel method to visualize individual oligodendrocytes and axon derived from a particular brain region in mouse white matter using a combinational injection of attenuated rabies virus and adeno-associated virus. Using this method, we found that some populations of oligodendrocytes in the corpus callosum predominantly ensheathed axons derived from motor cortex or sensory cortex, while others ensheathed axons from both brain regions, suggesting heterogeneity in preference of myelination toward a particular subtype of neurons. Moreover, our newly established method is a versatile tool for analyzing precise morphology of each oligodendrocyte in animal models for demyelinating disorders and addressing the role of oligodendrocyte in higher brain functions. GLIA 2016. GLIA 2017;65:93-105.

Post-partum hypoglycemia and hypothermia as first manifestations of lymphocytic adenohypophysitis: A case report.

Lymphocytic adenohypophysitis is a very rare autoimmune disease characterized by an anterior pituitary infiltration of lymphocytes that cause various symptoms, such as headache, visual disturbance, and hypopituitarism. Lymphocytic adenohypophysitis is more common in women and has a remarkable association with the perinatal period. Recently, we experienced a case of lymphocytic adenohypophysitis shortly after delivery. A 37-year-old primiparous woman delivered her baby at 38 weeks' gestation. The next morning, she presented symptoms of hypoglycemia and hypothermia. Blood testing revealed hypoadrenalism and hypothyroidism. Pituitary magnetic resonance imaging showed characteristic findings consistent with lymphocytic adenohypophysitis. We immediately initiated medication with steroids and levothyroxine. Currently, her pituitary size has normalized and its function has fully recovered. Physical stress resulting from labor and delivery may unmask subclinical lymphocytic adenohypophysitis. Practitioners should keep in mind the possibility of lymphocytic adenohypophysitis in any pregnant women with symptoms of hypoglycemia and hypothermia after delivery.

On the Spike Train Variability Characterized by Variance-to-Mean Power Relationship.

We propose a statistical method for modeling the non-Poisson variability of spike trains observed in a wide range of brain regions. Central to our approach is the assumption that the variance and the mean of interspike intervals are related by a power function characterized by two parameters: the scale factor and exponent. It is shown that this single assumption allows the variability of spike trains to have an arbitrary scale and various dependencies on the firing rate in the spike count statistics, as well as in the interval statistics, depending on the two parameters of the power function. We also propose a statistical model for spike trains that exhibits the variance-to-mean power relationship. Based on this, a maximum likelihood method is developed for inferring the parameters from rate-modulated spike trains. The proposed method is illustrated on simulated and experimental spike trains.

Anorectal abscess during pregnancy.

Anorectal symptoms and complaints caused by hemorrhoids or anal fissures are common during pregnancy. It is known that one-third of pregnant women complain of anal pain in the third trimester. Anal pain may be caused by a wide spectrum of conditions, but if it begins gradually and becomes excruciating within a few days it may indicate anorectal abscess. We experienced a case of anorectal abscess during pregnancy which was diagnosed by magnetic resonance imaging and treated by incision and seton drainage at 36 weeks of gestation, followed by a normal spontaneous delivery at 38 weeks of gestation. To our knowledge, this is the first case report of anorectal abscess during pregnancy in the English-language published work. The clinical course of our case and clinical considerations of anorectal abscesses are discussed.

Information transmission using non-poisson regular firing.

In many cortical areas, neural spike trains do not follow a Poisson process. In this study, we investigate a possible benefit of non-Poisson spiking for information transmission by studying the minimal rate fluctuation that can be detected by a Bayesian estimator. The idea is that an inhomogeneous Poisson process may make it difficult for downstream decoders to resolve subtle changes in rate fluctuation, but by using a more regular non-Poisson process, the nervous system can make rate fluctuations easier to detect. We evaluate the degree to which regular firing reduces the rate fluctuation detection threshold. We find that the threshold for detection is reduced in proportion to the coefficient of variation of interspike intervals.

Laparoscopic repair of a post-myomectomy spontaneous uterine perforation accompanied by a bizarre tumor resembling polypoid endometriosis.

Among various long-term complications after previous myomectomy, increasing risk of uterine rupture or dehiscence during pregnancy, and in particular during labor, has been widely recognized. In contrast, the world literature includes no case report of spontaneous uterine perforation or rupture after myomectomy in a nonpregnant woman, and only 1 case of iatrogenic uterine perforation after uterine artery embolization has been reported. Recently, we encountered an extremely rare case of spontaneous uterine perforation after previous myomectomy accompanied by a bizarre tumor resembling polypoid endometriosis, which was successfully treated via laparoscopic surgery. The patient reported genital bleeding and lower abdominal pain. Preoperative magnetic resonance imaging and intraoperative findings clearly demonstrated the presence of a uterine wall defect and a multicystic tumor that had developed from the perforated portion of the uterus. The patient underwent successful laparoscopic surgery for repair of the perforated uterus and resection of the tumor. The clinicopathologic diagnosis of the tumor was tentatively confirmed as an endometriosis-like lesion resembling polypoid endometriosis. We speculate that the cause of the tumor was retrograde menstruation, as in the pathogenesis of endometriosis.

Rupture of renal artery aneurysm during the early post-partum period.

Rupture of renal artery aneurysm associated with pregnancy is an uncommon condition. It is known that almost all previously reported cases have occurred during pregnancy. We experienced a case of rupture of renal artery aneurysm during the early post-partum period which was diagnosed by computed tomography and treated by angiographic embolization. To our knowledge, only two cases of rupture of renal artery aneurysm during the post-partum period have been reported in the English-language published work. An early diagnosis of rupture of renal artery aneurysm during the post-partum period is very challenging because the clinical symptoms of this condition are acute abdominal, flank or back pain, which are relatively common signs caused by more common post-partum complications. However, rupture of renal artery aneurysm is a life-threatening emergency condition requiring prompt diagnosis and treatment. The possibility of a rupture of renal artery aneurysm should be considered in any pregnant women with symptoms of an acute abdomen with hemorrhagic shock.

Angiographic findings after vaginal gauze packing: New insight into an old technique.

We had a transferred case of cervical ectopic pregnancy with hemorrhagic shock at 6 weeks of gestation. Upon arrival at hospital, we performed tight and full vaginal gauze packing to push the uterus upward to control the patient's hemorrhage. Following stabilization of her general condition, she was treated with uterine artery embolization. Using angiography, the effectiveness of vaginal gauze packing for emergency hemostasis by the presumed mechanism of impairing blood flow through the uterine artery was demonstrated. To our knowledge, there are no reports that have previously demonstrated angiographic findings similar to ours after vaginal gauze packing. Vaginal gauze packing is an effective, rapid, and convenient hemostatic procedure able to be carried out in a time-sensitive and challenging situation. As a result, this procedure gives clinicians more time to improve the patients' general status and arrange for transfusion and further definitive treatment.

Maternal carbon dioxide level during labor and its possible effect on fetal cerebral oxygenation: mini review.

During pregnancy, and especially during labor, the maternal carbon dioxide level declines considerably. Maternal carbon dioxide levels show a close relation with fetal carbon dioxide levels. The latter affects fetal cerebral oxygenation by regulating cerebral blood flow and shifting the oxyhemoglobin dissociation curve. In addition, maternal hypocapnia appears to impair placental oxygen transfer. Thus, maternal hyperventilation may interfere with optimal fetal cerebral oxygenation. Here, we provide a brief overview of the literature relevant to this issue.

Estimating effective reproduction number revisited.

Accurately estimating the effective reproduction number is crucial for characterizing the transmissibility of infectious diseases to optimize interventions and responses during epidemic outbreaks. In this study, we improve the estimation of the effective reproduction number through two main approaches. First, we derive a discrete model to represent a time series of case counts and propose an estimation method based on this framework. We also conduct numerical experiments to demonstrate the effectiveness of the proposed discretization scheme. By doing so, we enhance the accuracy of approximating the underlying epidemic process compared to previous methods, even when the counting period is similar to the mean generation time of an infectious disease. Second, we employ a negative binomial distribution to model the variability of count data to accommodate overdispersion. Specifically, given that observed incidence counts follow a negative binomial distribution, the posterior distribution of secondary infections is obtained as a Dirichlet multinomial distribution. With this formulation, we establish posterior uncertainty bounds for the effective reproduction number. Finally, we demonstrate the effectiveness of the proposed method using incidence data from the COVID-19 pandemic.

Multivariate epidemic count time series model.

An infectious disease spreads not only over a single population or community but also across multiple and heterogeneous communities. Moreover, its transmissibility varies over time because of various factors such as seasonality and epidemic control, which results in strongly nonstationary behavior. In conventional methods for assessing transmissibility trends or changes, univariate time-varying reproduction numbers are calculated without taking into account transmission across multiple communities. In this paper, we propose a multivariate-count time series model for epidemics. We also propose a statistical method for estimating the transmission of infections across multiple communities and the time-varying reproduction numbers of each community simultaneously from a multivariate time series of case counts. We apply our method to incidence data for the novel coronavirus disease 2019 (COVID-19) pandemic to reveal the spatiotemporal heterogeneity of the epidemic process.

On the relation between encoding and decoding of neuronal spikes.

Neural coding is a field of study that concerns how sensory information is represented in the brain by networks of neurons. The link between external stimulus and neural response can be studied from two parallel points of view. The first, neural encoding, refers to the mapping from stimulus to response. It focuses primarily on understanding how neurons respond to a wide variety of stimuli and constructing models that accurately describe the stimulus-response relationship. Neural decoding refers to the reverse mapping, from response to stimulus, where the challenge is to reconstruct a stimulus from the spikes it evokes. Since neuronal response is stochastic, a one-to-one mapping of stimuli into neural responses does not exist, causing a mismatch between the two viewpoints of neural coding. Here we use these two perspectives to investigate the question of what rate coding is, in the simple setting of a single stationary stimulus parameter and a single stationary spike train represented by a renewal process. We show that when rate codes are defined in terms of encoding, that is, the stimulus parameter is mapped onto the mean firing rate, the rate decoder given by spike counts or the sample mean does not always efficiently decode the rate codes, but it can improve efficiency in reading certain rate codes when correlations within a spike train are taken into account.

Reliable predictors of neonatal immune thrombocytopenia in pregnant women with idiopathic thrombocytopenic purpura.

Of infants born to women with idiopathic thrombocytopenic purpura (ITP), about 10-15% have transient neonatal immune thrombocytopenic purpura (NITP). Of concern is the lack of a reliable predictor for NITP. We conducted a retrospective study of all pregnancies with ITP at Osaka University Hospital over the past 16 years analyzing a total of 127 pregnancies in 88 women with ITP to assess the predictive value of various clinical factors regarding neonatal platelet count in the current pregnancy. We also reviewed the literature concerning ITP in pregnancy and NITP prediction. Neonatal platelet counts were less than 100 × 10(9)/L in 20 of 130 neonates (15.4%), less than 50 × 10(9)/L in 11 neonates (8.5%), and less than 20 × 10(9)/L in three neonates (2.3%). There was a strong correlation between the first and second sibling regarding the occurrence and the severity of NITP with Spearman correlation coefficient of 0.55 (P = 0.001) at birth and 0.63 (P < 0.0001) at nadir after birth. A maternal platelet count less than 100 × 10(9)/L at delivery showed a statistical trend for an association with the occurrence of NITP (P = 0.043). Moreover, maternal ITP refractory to splenectomy correlated with a higher risk for fetal or neonatal ICH according to the review of the literature. In conclusion, pregnant women who have had a previous offspring with NITP or who have ITP refractory to splenectomy may be at particular risk of delivering an offspring with significant NITP. Management decisions, including mode of delivery, may be altered by the degree of risk for potentially severe NITP.

Perioperative Serum Creatinine Change and Delayed Urologic Complications Following Total Laparoscopic Hysterectomy for Benign Indications.

Objectives: The objective of the study was to investigate the association between perioperative serum creatinine change and delayed urologic complications following total laparoscopic hysterectomy (TLH) for benign indications. Materials and Methods: A total of 510 cases (503 cases without delayed urologic injuries and 7 cases with delayed urologic injuries) in which TLH was performed for benign indications were retrospectively reviewed. The patient characteristics and surgical outcomes were compared between patients with and without delayed urologic injuries. Laboratory markers (serum creatinine level at the preoperative and postoperative periods, white blood cell [WBC] ratio, and C-reactive protein [CRP] ratio) were analyzed to evaluate the diagnostic value of these laboratory markers. Results: There were no statistically significant differences in age, parity, body mass index, the presence of diabetes mellitus, preoperative GnRH agonist use, previous history of abdominal surgery or the performance of adnexal surgery, ASRM score, the presence of cul-de-sac obliteration, operative time, blood loss or weight of the resected specimens between the two groups. The proportions of patients who showed an elevated creatinine level on postoperative day 1 was significantly higher in the delayed urologic injury group (9.9% vs. 57%, P < 0.001). The combination of the three laboratory markers yielded an area under the ROC curve value of 0.75 (95% confidence interval, 0.491-1) in the detection of delayed urologic injuries. Conclusion: A change in the serum creatine level over baseline after surgery may indicate the possibility of urologic injuries. The combination of creatinine change and other factors, such as WBC or CRP would be helpful for detecting urologic complications after TLH.

Pseudomyxoma peritonei originating from colorectal cancer during pregnancy.

Pseudomyxoma peritonei is an extremely rare condition characterized by the presence of gelatinous ascites and disseminated intra-peritoneal mucinous tumors. To our knowledge, there have been only two case reports of pseudomyxoma peritonei during pregnancy in 2009, both of which originated from the appendix. We present the first case of pseudomyxoma peritonei originating from colorectal cancer during pregnancy. Prenatal ultrasound examination of a 34-year-old, asymptomatic woman revealed characteristic features of pseudomyxoma peritonei at 24 weeks gestation. At laparotomy, both ovaries were involved with copious amounts of mucinous tumors and fluid, an advanced colorectal cancer had invaded the peritoneal cavity and multiple disseminated tumors were noted around the intraperitoneal cavity. All clinicians practicing obstetrics and gynecology must consider the possibility of a malignant neoplasm presenting in a pregnant woman and should recognize the highly characteristic features of pseudomyxoma peritonei to enable detection of this rare condition incidentally during routine screening ultrasound examinations.

Fetal and neonatal anemia associated with anti-Jr(a) : a case report showing a poorly hemolytic mechanism.

Although recently published case reports suggest the significance of Jr(a) alloimmunization in the obstetric setting, the involved mechanism still remains unclear. Here we report a case of severe fetal and neonatal anemia associated with anti-Jr(a) alloimmunization, which was successfully managed using Doppler assessment of peak systolic velocity of the fetal middle cerebral artery (MCA-PSV). A Japanese woman with anti-Jr(a) (titer 1024) was referred to our department at 20 weeks' gestation. As fetal MCA-PSV exceeded 1.5 multiple of median, labor was induced and a female neonate of 1998 g was delivered vaginally at 33 weeks and 5 days of gestation. The infant's hematocrit and hemoglobin levels were 25.4% and 82 g/L, respectively, but her total bilirubin level (15 µmol/L; 0.9 mg/dL) and reticulocyte counts (4.5%) were low. During the course, the infant showed no apparent signs of hemolysis. Jr(a) alloimmunization should be recognized as a possible cause of fetal anemia with no direct hemolytic process.