bluuebunny/crossref_metadata_2025 huggingface dataset:
The efficacy evaluation of partial nephrectomy with selective renal artery branch occlusion by laparoscopy
Authors: Wang Chun-Hui , Li Chun-Sheng , Jiang Ying , Zhang Hao , Mu Ha-Da , Bao Guo-Chang
Published: June 2021

Background:

To investigate the clinical application and effect of laparoscopic partial nephrectomy with renal artery branch occlusion in the treatment of early renal tumors.

Methods:

A retrospective analysis was conducted on the clinical data of 15 cases of renal tumor patients who underwent partial nephrectomy by laparoscopic selective renal artery branch occlusion in our department from January 2017 to January 2018. Nine male patients and 6 female patients were aged 46 to 65 years, with an average age of 54.3 ± 7.2 years. The diameters of tumors were 2.2 to 4.0 cm, with an average of 3.3 ± 0.7 cm. There are 10 tumors locating on the left side and 5 on the right side. Preoperative renal glomerular filtration rate (GFR) were 77.3 to 61.9 mL/min with an average of 47.6 ± 7.5 mL/min. All patients’ diseased kidneys underwent renal computer tomography angiography examination before surgery. And the diseased kidney underwent reexamination of renal GFR. The operation time, renal artery branch occlusion time, intraoperative blood loss, postoperative hospital stay, changes of renal function, and complications were evaluated.

Results:

All surgery were completed successfully, the surgery time was 136.7 ± 15.2 min, intraoperative renal artery branch occlusion time was 21.3 ± 4.5 min, the intraoperative blood loss was 223.3 ± 69.5 mL, the postoperative hospital stay was 6.5 ± 1.7 days, and the postoperative 1-month GFR was 49.5 ± 6.6 mL/min. There was no significant difference between the renal GFR before and after surgery (P > .05). There was no blood transfusion and transfer open surgery cases. The patients were followed up for 3 to 15 months without complications.

Conclusions:

Partial nephrectomy with selective renal artery branch occlusion by laparoscopy is a safe, feasible, and effective method for the treatment of early renal cancer. It makes good use of the technical advantages of clear operation field and fine operation of laparoscopic surgery, avoids the heat ischemia process of the whole kidney, and can better protect the renal function.
Multi-center and randomized controlled clinical study of electro-acupuncture intervention in the treatment of Bell's facial paralysis
Authors: Zhang Xuelian , Feng Sifeng , Xiong Youlong , Deng Xingyou , Dai Anhong , Zhou Yihao , Shi Jing , Zhang Xiahui
Published: June 2021

Backgroud:

Bell's facial paralysis is a disease that seriously endangers human health. Electroacupuncture therapy is considered to be effective in the treatment of this disease, but there is still a great controversy whether to use electroacupuncture in patients in the acute phase, and there is a lack of multi-center, large-sample clinical studies on different electroacupuncture parameters in the treatment of Bell's facial paralysis. The purpose of this study is to provide high-quality evidence for the clinic through multi-center, large-sample clinical study.

Design:

In this multicenter, double-blinded, randomized controlled clinical trial, a total of 330 patients with acute Bell's palsy aged 18 to 70 years were randomly divided into experimental group and control group. The experimental group was divided into 4 groups (A, B, C, D) according to different electroacupuncture parameters, with 66 participants in each group. The control group received ordinary acupuncture. The entire study period was 60 days, including 30 days of treatment observation and 1 month follow-up. House-Brackmann scale and facial nerve electrophysiological examination were used as the main efficacy evaluation indexes, Chinese medicine syndrome score evaluation scale and sequelae scale of Bell palsy were used as secondary efficacy indexes, and blood routine was used as safety indexes. The clinical evaluation time was before, 7 days after treatment, 14 days after treatment, 21 days after treatment, 28 days after treatment, and 1 month follow-up. The primary outcome of the postacupuncture effect were investigated by paired T-test, and the continuous outcome variables will be analyzed with univariate repetitive measurement deviation analysis. Adverse events will be noted and recorded for the safety evaluation.

Conclusion:

In this study, electroacupuncture wave type and frequency were used as control conditions to explore the efficacy and safety of electroacupuncture in the treatment of patients with acute Bell's palsy under different parameters. This study will provide reasonable stimulation parameters for electroacupuncture treatment of patients with acute Bell's palsy and provide strong evidence for the safety and effectiveness of electroacupuncture interventional therapy in acute stage.

CHICTR registration number:

ChiCTR1800015882. Registered in April 2018.
HBV-related acute-on-chronic liver failure with underlying chronic hepatitis has superior survival compared to cirrhosis
Authors: Liu Xiaohui , Zhang Jing , Wei Xinhuan , Duan Zhongping , Liu Hongqun , Chen Yu , Liu Yali , Lee Samuel S.
Published: June 2021

Background

Acute-on-chronic liver failure (ACLF) is divided into three types according to the underlying liver disease: non-cirrhosis (type A), compensated cirrhosis (type B) and decompensated cirrhosis (type C). However, whether the underlying chronic liver diseases impact the ACLF prognosis is not clear. The present study aimed to compare the characteristics and outcomes of type A and type B hepatitis B virus (HBV)-ACLF patients.

Methods

According to the European Association for the Study of Liver-Chronic Liver Failure (EASL-CLIF) diagnostic criteria, 86 type A HBV-ACLF and 71 type B HBV-ACLF were prospectively enrolled. The demography and laboratory data, organ failures, ACLF grades and prognosis were evaluated. Univariate and multivariate Cox regression analyses were performed to analyze the prognostic factors.

Results

The 28-day and 90-day mortality rates of type A and type B ACLF were 20.9 vs. 60.6% and 34.9 vs. 73.2%, respectively (both P < 0.001). Patients with type A ACLF were younger, had higher viral load and higher levels of alanine aminotransferase and aspartate aminotransferase, platelet count, serum albumin and sodium, international normalized ratio and alpha-fetoprotein, lower rate of ascites, lower Child-Pugh scores and CLIF sequential organ failure assessment scores, higher rate of coagulation failure. Type B ACLF had more renal and cerebral failure. Cirrhosis was one of the independent prognostic factors [hazard ratio, 2.4 (95% CI, 1.451–3.818) P < 0.001].

Conclusion

ACLF developing on noncirrhotic chronic hepatitis B had more serious liver inflammation but fewer extrahepatic organ failures and better outcome than ACLF developing from compensated HBV cirrhosis.
A Case of Combined Central and Peripheral Demyelination Associated With Antineurofascin 155 Antibodies and Paternal History of Multiple Sclerosis
Authors: Lambrianides Sakis , Kinnis Evgenios , Cleanthous Michele , Myrianthopoulou Panayiota , Leonidou Eleni , Kyriakides Theodoros
Published: June 2021

Introduction:

Combined central and peripheral demyelination (CCPD) is a term used to describe a rare condition involving demyelinating lesions of both the central and the peripheral nervous system. Its etiology remains unclear, and a pathogenic role of cell-mediated and/or humoral immunity has been proposed. A number of patients with CCPD are positive to antineurofascin (anti-NF), antigalactocerebroside, and antilactosylseramide antibodies. The relation between CCPD and multiple sclerosis (MS) is unclear.

Case Report:

We report the case of a 30-year-old man who was referred for evaluation after having episodes of numbness and gait impairment worsened by intravenous Methylprednisolone and was found to have demyelination in both central and peripheral nervous system. The patient was eventually diagnosed with anti-NF 155 CCPD and received multiple courses of intravenous immunoglobulin without significant improvement, while he remained stable under Rituximab. Interestingly, the patient’s father suffered from a mild form of relapsing remitting MS.

Conclusion:

Our case emphasizes that clinicians need to keep in mind the possibility of a coexisting demyelination in both central and peripheral nervous system, even in patients with a family history of MS. The need for a timely diagnosis is imperative since several drugs used in the management of MS can worsen the patient’s symptoms in CCPD. This is, to our knowledge, the first reported case of a patient with anti-NF 155 positive CCPD and a family history of MS.
Parkinsonism-hyperpyrexia Syndrome After Amantadine Withdrawal
Authors: dos Santos Daniel T. , Imthon Alexandre K. , Strelow Matheus Z. , Pille Arthur , Schumacher-Schuh Artur F.
Published: June 2021

Introduction:

Parkinsonism-hyperpyrexia syndrome (PHS) is a rare and potentially fatal complication of Parkinson disease (PD) characterized by a neuroleptic malignant-like syndrome due to abrupt discontinuation of antiparkinsonian medications.

Case Report:

A 79-year-old woman with late-stage PD presented at the hospital with neuropsychiatric and uncontrolled parkinsonian motor symptoms. Soon after the abrupt discontinuation of amantadine, the patient suddenly presented with global rigidity, global unresponsiveness, diaphoresis, tachycardia, recurrent hyperpyrexia, and a mildly elevated creatine kinase, which lead to the diagnosis of PHS. Amantadine was then reinitiated and her symptoms resolved within 10 days.

Conclusions:

Amantadine is an antiparkinsonian medication scarcely associated with PHS. The few reported cases are further summarized and discussed in this article. This case highlights the importance of early recognition of PHS, which may be caused by changes in other antiparkinson agents such as amantadine, and the need to slowly titrate such agents.
Wall-Eyed Bilateral Internuclear Ophthalmoplegia (WEBINO) in a Patient With a Unilateral Midbrain Infarction
Authors: Jo Yoon-Sik , Hong Jun Yeong , Kim Si Yeon , Na Sang-Jun
Published: June 2021

Introduction:

Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) is a rare variation of internuclear ophthalmoplegia associated with bilateral lesions of the medial longitudinal fasciculus.

Case Report:

In this case, the edematous lesions of the ipsilateral midbrain infarction appeared to compress the contralateral medial longitudinal fasciculus, resulting in WEBINO. Treatment of focal cerebral edema caused by ischemic stroke is still under debate. However, in this case, antiedema treatment was implemented to prevent the sequelae of the edematous lesion caused by a midbrain infarction, and a relatively rapid improvement of ocular symptoms was observed.

Conclusion:

Herein, we report a rare case of WEBINO caused by a unilateral midbrain infarction in which the patient experienced edema-related neurological deficits. This case provides evidence that early antiedema therapy may benefit patients with similar presentations.
Effects of Case Management on Risky Sexual Behaviors and Syphilis Among HIV-Infected Men Who Have Sex With Men in China: A Randomized Controlled Study
Authors: Xie Nianhua , Hu Xuejiao , Yan Han , Ruan Lianguo , Liu Cong , Hu Rong , Ma Hongfei , Luo Yanhe , Liu Li , Wang Xia
Published: June 2021

Background

The prevalence of syphilis is very high in human immunodeficiency virus (HIV)–positive men who have sex with men (MSM), and effective interventions are needed to educate HIV-positive individuals about behavioral and biological risk factors. Therefore, we developed a standard case management process and conducted a randomized controlled study to investigate the impact on risky sexual behaviors and syphilis in HIV-positive MSM.

Methods

Men who have sex with men (n = 220) were enrolled and randomized to the case management intervention group and the control group between May 2016 and January 2017. The control group received routine HIV-related care. In addition to routine HIV-related care, those in the intervention group regularly received extended services from a well-trained case manager. Epidemiological information was collected during the baseline face-to-face interviews by a trained investigator. Serological tests for syphilis and assessments of risky sexual behaviors were performed at baseline and 6 and 12 months after the initiation of treatment.

Results

The syphilis incidence rates in the intervention and control groups were 11.3 per 100 person-years and 20.6 per 100 person-years, respectively. The multivariable-adjusted hazard ratio (95% confidence inter) for syphilis in case management group was 0.34 (0.14–0.87). The percentages of participants who resumed risky sexual behaviors in both groups were significantly reduced (P < 0.05) but did not significantly differ between the 2 groups.

Conclusions

A case management intervention reduced the incidence of syphilis in HIV-positive MSM. We should further increase the content of case management on the basis of providing routine HIV-related care to those people.
The Application of the Divine Proportion for the Construction of the Visualized Treatment Objective in Craniofacial Surgery
Authors: Sambataro Sergio , Cicciù Marco , Nocini Riccardo , Crimi Salvatore , Bianchi Alberto , Ciancio Francesco , Stumpo Chiara , Bocchieri Salvatore , Fiorillo Luca , Caprioglio Alberto
Published: June 2021

Aesthetics and function of maxillofacial district are closely related and could interfere with patient psychological conditions. The aim of this paper is to describe and to analyze the procedures necessary for a proper surgical visualized treatment objective (VTO) realization through the use of the tracing on lateral head film, applying the divine proportion (or golden ratio) in certain steps. The method described is easy to realize, cheap and help both orthodontist and maxillo-facial surgeon to communicate each other and to the patients.

For the following article, digital research and handheld research on surgical VTO planning for patients with skeletal or dentoalveolar severe deformities managed by surgeons and orthodontics were used. The research included articles in English published on dental and maxillofacial surgery journals.

The surgical VTO consists of a “previsualization” of the objectives in order to make the desired changes for the individual patient. The result can thus be visualized and pre-evaluated rather than just imagined by the mind's eye. To simplify the procedure, the surgical VTO has been divided into 11 steps. The accurate model of the surgical result is fundamental in the treatment of dentofacial deformities. These predictions are intended to guide the treatment towards the desired result, to give the patient a reasonable preview of the outcome, and to ensure communication between the orthodontist and the surgeon.

This technique proves to be effective in planning surgical treatment and it allows the clinician to view changes before, during, and after orthognathic surgery. The skeletal, dental, and aesthetic complete cephalometric evaluation is the key point to the long-term success of the results.
Morphometric Analysis of the Glenoid Fossa in the Skull Base
Authors: Karayol Kudret Cem , Karayol Sunay Sibel
Published: June 2021

Objective:

The aim of this study was to investigate the possible relationship between disc displacement and the presence of reduction by comparing condyle anteroposterior (AP) diameter, condyle height, mandibular fossa AP diameter, and mandibular fossa depth.

Methods:

A total of 588 joints of 294 patients were included in the study for evaluation. Disc displacement and the presence of reduction, condyle AP diameter, condyle height, mandibular fossa AP diameter, and mandibular fossa depth were evaluated.

Results:

Of the 588 temporomandibular joint examined in the study, there was disc displacement in 141 (24%) and no disc displacement in 447 (76%). Of the joints with disc displacement, reduction was observed in 53 (9%) and not in 88 (15%).

A statistically significant correlation was determined between condyle AP diameter and disc displacement (P = 0.00); in the cases with disc displacement, the condyle AP diameter was measured smaller. A statistically significant correlation was determined with condyle height, mandibular fossa AP diameter, and fossa depth. In the patients with disc displacement, the condyle height value was lower and the measured values of the mandibular fossa AP diameter and mandibular fossa depth were higher (P = 0.00). A statistically significant relationship was determined between the presence of reduction and age, condyle AP diameter, condyle height, and articular eminence depth.

Conclusions:

In conclusion, a deep and wide mandibular fossa, and a short and small condyle lay the ground for disc displacement in the temporomandibular joint.
The economic potential of metalliferous sub-volcanic brines
Authors: Blundy Jon , Afanasyev Andrey , Tattitch Brian , Sparks Steve , Melnik Oleg , Utkin Ivan , Rust Alison
Published: June 2021

The transition to a low-carbon economy will increase demand for a wide range of metals, notably copper, which is used extensively in power generation and in electric vehicles. Increased demand will require new, sustainable approaches to copper exploration and extraction. Conventional copper mining entails energy-intensive extraction of relatively low-grade ore from large open pits or underground mines and subsequent ore refining. Most copper derives ultimately from hot, hydrous magmatic fluids. Ore formation involves phase separation of these fluids to form copper-rich hypersaline liquids (or ‘brines') and subsequent precipitation of copper sulfides. Geophysical surveys of many volcanoes reveal electrically conductive bodies at around 2 km depth, consistent with lenses of brine hosted in porous rock. Building upon emerging concepts in crustal magmatism, we explore the potential of sub-volcanic brines as anin situsource of copper and other metals. Using hydrodynamic simulations, we show that 10 000 years of magma degassing can generate a Cu-rich brine lens containing up to 1.4 Mt Cu in a rock volume of a few km3at approximately 2 km depth. Direct extraction of metal-rich brines represents a novel development in metal resource extraction that obviates the need for conventional mines, and generates geothermal power as a by-product.
ASSESSMENT OF POTENTIAL SARS-CoV-2 VIRUS N GENE INTEGRATION INTO HUMAN GENOME REVEALS NO SIGNIFICANT IMPACT ON RT-qPCR COVID-19 DIAGNOSTIC TESTING
Authors: Briggs Erica , Ward William , Rey Sol , Law Dylan , Nelson Katharine , Bois Michael , Ostrov Nili , Lee Henry H. , Laurent Jon M. , Mita Paolo
Published: June 2021

The SARS Coronavirus 2 (SARS-CoV-2) pandemic presents new scientific and scale-up challenges for diagnostic capabilities worldwide. The gold standard diagnostic for SARS-CoV-2 infection is a reverse transcription/quantitative PCR (RT-qPCR) which targets the viral genome, an assay that has now been performed on millions of patient specimens worldwide regardless of symptomatic status. Recently Zhang et al. suggested the possibility that the SARS-CoV-2 N gene could integrate into host cell DNA through the action of the LINE-1 retrotransposon, a mobile element that is potentially active in human somatic cells, thereby calling into question the veracity of N-gene based RT-qPCR for detection of SARS-CoV-2 infection. Accordingly, we assessed the potential impact of these purported integration events on nasal swab specimens tested at our clinical laboratory. Using an N-gene based RT-qPCR assay, we tested 768 arbitrarily selected specimens and identified 2 samples which resulted in a positive detection of viral sequence in the absence of reverse transcriptase, a necessary but not sufficient signal consistent with possible integration of the SARS-CoV-2 N gene into the host genome. Regardless of possible viral N gene integration into the genome, in this small subset of samples, all patients were still positive for SARS-CoV-2 infection, as indicated by a much lower Ct value for reactions performed in the presence of reverse transcriptase (RT) versus reactions performed without RT. Moreover, one of the two positives observed in the absence of RT also tested positive when using primers targeting ORF1ab, a gene closer to the 5’ end of the genome. These data are inconsistent with the N gene integration hypothesis suggested by the studies by Zhang et al., and importantly, our results suggest little to no practical impact of possible SARS-CoV-2 genome integration events on RT-qPCR testing.

COMPETING INTEREST STATEMENT

The authors of this study are employees of the Pandemic Response Lab (PRL)/ReOpen Diagnostics, a private company performing SARS-CoV-2 RT-qPCR based testing, an area of interest of this study.
Carriage of ESBL-producing Enterobacterales in wastewater treatment plant workers and surrounding residents - The AWARE Study
Authors: Rodríguez-Molina Daloha , Berglund Fanny , Blaak Hetty , Popa Marcela , Flach Carl-Fredrik , Kemper Merel , Marutescu Luminita , Pircalabioru Gratiela , Spießberger Beate , Weinmann Tobias , Wengenroth Laura , Chifiriuc Mariana Carmen , Larsson D. G. Joakim , Radon Katja , Nowak Dennis , Wieser Andreas , de Roda Husman Ana Maria , Schmitt Heike
Published: June 2021

Purpose

To investigate whether wastewater treatment plant (WWTP) workers and residents living in close proximity to a WWTP have elevated carriage rates of ESBL-producing Enterobacterales, as compared to the general population.

Methods

From 2018 to 2020, we carried out a cross-sectional study in Germany, the Netherlands, and Romania among WWTP workers (N=344), nearby residents (living ≤ 300 meters away from WWTPs; N=431) and distant residents (living ≥ 1000 meters away = reference group; N=1165). We collected information on potential confounders via questionnaire. Culture of participants’ stool samples was performed with ChromID®-ESBL agar plates and species identification with MALDI-TOF-MS. We used logistic regression to estimate the odds ratio (OR) for carrying ESBL-producingE. coli(ESBL-EC). Sensitivity analyses included stratification by country and interaction models using country as secondary exposure.

Results

Prevalence of ESBL-EC was 11% (workers), 29% (nearby residents), and 7% (distant residents), and higher in Romania (28%) than in Germany (7%) and the Netherlands (6%). Models stratified by country showed that within the Romanian population, WWTP workers are about twice as likely (aOR = 2.34, 95% CI: 1.22-4.5) and nearby residents about three times as likely (aOR = 3.17, 95% CI: 1.8-5.59) to be ESBL-EC carriers, when compared with distant residents.

Conclusions

In stratified analyses by country, we found an increased risk for carriage of ESBL-EC in Romanian workers and nearby residents. This effect was higher for nearby residents than for workers, which suggests that, for nearby residents, factors other than the local WWTP could contribute to the increased carriage.
Microbiome profiles are associated with cognitive functioning in 45-month-old children
Authors: Streit Fabian , Prandovszky Emese , Send Tabea , Zillich Lea , Frank Josef , Sabunciyan Sarven , Foo Jerome , Sirignano Lea , Lange Bettina , Bardtke Svenja , Hatfield Glen , Witt Stephanie H , Gilles Maria , Rietschel Marcella , Deuschle Michael , Yolken Robert
Published: June 2021

Prenatal, perinatal, and postnatal factors have been shown to shape neurobiological functioning and alter the risk for mental disorders later in life. The gut microbiome is established early in life, and interacts with the brain via the brain-immune-gut axis. However, little is known about how the microbiome relates to early-life cognitive functioning in children. The present study, where the fecal microbiome of 380 children was characterized using 16s rDNA and metagenomic sequencing aimed to investigate the association between the microbiota and cognitive functioning of children at the age of 45 months measured with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III).

Overall the microbiome profile showed a significant association with cognitive functioning. A strong correlation was found between cognitive functioning and the relative abundance of an unidentified genus of the family Enterobacteriaceae. Follow-up mediation analyses revealed significant mediation effects of the level of this genus on the association of maternal smoking during pregnancy and current cigarette smoking with cognitive function. Metagenomic sequencing of a subset of these samples indicated that the identified genus was most closely related to Enterobacter asburiae. Analysis of metabolic potential showed a nominally significant association of cognitive functioning with the microbial norspermidine biosynthesis pathway.

Our results indicate that alteration of the gut microflora is associated with cognitive functioning in childhood. Furthermore, they suggest that the altered microflora might interact with other environmental factors such as maternal cigarette smoking. Interventions directed at altering the microbiome should be explored in terms of improving cognitive functioning in young children.
In vivo kinetics of SARS-CoV-2 infection and its relationship with a person’s infectiousness
Authors: Ke Ruian , Zitzmann Carolin , Ho David D. , Ribeiro Ruy M. , Perelson Alan S.
Published: June 2021

The within-host viral kinetics of SARS-CoV-2 infection and how they relate to a person’s infectiousness are not well understood. This limits our ability to quantify the impact of interventions on viral transmission. Here, we develop data-driven viral dynamic models of SARS-CoV-2 infection and estimate key within-host parameters such as the infected cell half-life and the within-host reproductive number. We then develop a model linking VL to infectiousness, showing that a person’s infectiousness increases sub-linearly with VL. We show that the logarithm of the VL in the upper respiratory tract (URT) is a better surrogate of infectiousness than the VL itself. Using data on VL and the predicted infectiousness, we further incorporated data on antigen and reverse transcription polymerase chain reaction (RT-PCR) tests and compared their usefulness in detecting infection and preventing transmission. We found that RT-PCR tests perform better than antigen tests assuming equal testing frequency; however, more frequent antigen testing may perform equally well with RT-PCR tests at a lower cost, but with many more false-negative tests. Overall, our models provide a quantitative framework for inferring the impact of therapeutics and vaccines that lower VL on the infectiousness of individuals and for evaluating rapid testing strategies.

Significance

Quantifying the kinetics of SARS-CoV-2 infection and individual infectiousness is key to quantitatively understanding SARS-CoV-2 transmission and evaluating intervention strategies. Here we developed data-driven within-host models of SARS-CoV-2 infection and by fitting them to clinical data we estimated key within-host viral dynamic parameters. We also developed a mechanistic model for viral transmission and show that the logarithm of the viral load in the upper respiratory tract serves an appropriate surrogate for a person’s infectiousness. Using data on how viral load changes during infection, we further evaluated the effectiveness of PCR and antigen-based testing strategies for averting transmission and identifying infected individuals.
Age reporting in the Brazilian COVID-19 vaccination database: What can we learn from it?
Authors: Turra Cássio M , Fernandes Fernando , Calazans Julia , Nepomuceno Marília R.
Published: June 2021

Age is a key variable for sciences and public planning. The demographic consequences of not measuring age correctly are manifold, including errors in mortality rates and population estimates, particularly at older ages. It also affects public programs because target populations depend on reliable population age distributions. In Brazil, the start of the vaccination campaign against COVID-19 marked the collection of new administrative data. Every citizen must be registered and need to show an identity document to get vaccinated. The requirement of proof-of-age documentation provides a unique opportunity for measuring the elderly population using a different database. This article examines the reliability of age distributions of men and women 80 years and older. We calculate various demographic indicators using data from the vaccination registration system and compare them to those from the target population estimates of the National Vaccination Plan, censuses, and population projections for Brazil and countries with high-quality population data. We show that requiring proof-of-age, such as in the vaccination records, increases data quality, mainly through the reduction of age heaping and age exaggeration. However, I.D. cards cannot fully solve wrong birth dates that result from weak historical registration systems. Thus, one should be careful when using estimates of the old age population living in some of the Brazilian regions, particularly the North, Northeast, and Center-West. Also, our analysis reveals a mismatch between the projected population by age, sex, and region, which guided the vaccination plan, and the number of vaccinated at ages 80 and older. The methodology developed to adjust the mortality rates used in the demographic projections is probably the main factor behind the disparities found.
Changes in non-oscillatory features of the cortical sensorimotor rhythm in Parkinson’s disease across age
Authors: Vinding Mikkel C. , Eriksson Allison , Ting Low Cassia Man , Waldthaler Josefine , Ferreira Daniel , Ingvar Martin , Svenningsson Per , Lundqvist Daniel
Published: June 2021

Parkinson’s disease (PD) is associated with changes in neural activity in the sensorimotor alpha and beta bands. Using magnetoencephalography (MEG), we investigated the role of spontaneous neuronal activity within the somatosensory cortex in a large cohort of early-to mid-stage PD patients (N = 78) and age- and sex matched healthy controls (N = 60) using source reconstructed resting-state MEG. We quantified features of the time series data in terms of oscillatory alpha power, beta power, and 1/f broadband characteristics using power spectral density, and also characterised transient beta burst events in the time-domain signals. We examined the relationship between these signal features and the patients’ disease state, symptom severity, age, sex, and cortical thickness.

PD patients and healthy controls differed on PSD broadband characteristics, with PD patients showing a steeper 1/f exponential slope and higher 1/f offset. PD patients further showed a steeper age-related decrease in the burst rate. Out of all the signal features of the sensorimotor activity, only burst rate was associated with increased severity of bradykinesia. Our study shows that general non-oscillatory features (broadband PSD slope and offset) of the sensorimotor signals are related to disease state and oscillatory burst rate scales with symptom severity in PD.
Task modulation of spatiotemporal dynamics in semantic brain networks: an EEG/MEG study
Authors: Rahimi Setareh , Farahibozorg Seyedeh-Rezvan , Jackson Rebecca , Hauk Olaf
Published: June 2021

How does brain activity in distributed semantic brain networks evolve over time, and how do these regions interact to retrieve the meaning of words? We compared spatiotemporal brain dynamics between visual lexical and semantic decision tasks (LD and SD), analysing whole-cortex evoked responses and spectral functional connectivity (coherence) in source-estimated electroencephalography and magnetoencephalography (EEG and MEG) recordings. Our evoked analysis revealed generally larger activation for SD compared to LD, starting in primary visual area (PVA) and angular gyrus (AG), followed by left posterior temporal cortex (PTC) and left anterior temporal lobe (ATL). The earliest activation effects in ATL were significantly left-lateralised. Our functional connectivity results showed significant connectivity between left and right ATLs and PTC and right ATL in an early time window, as well as between left ATL and IFG in a later time window. The connectivity of AG was comparatively sparse. We quantified the limited spatial resolution of our source estimates via a leakage index for careful interpretation of our results. Our findings suggest that semantic task demands modulate visual and attentional processes early-on, followed by modulation of multimodal semantic information retrieval in ATLs and then control regions (PTC and IFG) in order to extract task-relevant semantic features for response selection. Whilst our evoked analysis suggests a dominance of left ATL for semantic processing, our functional connectivity analysis also revealed significant involvement of right ATL in the more demanding semantic task. Our findings demonstrate the complementarity of evoked and functional connectivity analysis, as well as the importance of dynamic information for both types of analyses.

Highlights

Semantic task demands affect activity and connectivity at different processing stages

Earliest task modulations occurred in posterior visual brain regions

ATL, PTC and IFG effects reflect task-relevant retrieval of multimodal information

ATL effects left-lateralised for activation but bilateral for functional connectivity

Dynamic evoked and connectivity data are essential to study semantic networks
Whole genome sequencing elucidates the species-wide diversity and evolution of fungicide resistance in the early blight pathogen Alternaria solani
Authors: Einspanier Severin , Susanto Tamara , Metz Nicole , Wolters Pieter J. , Vleeshouwers Vivianne G.A.A. , Lankinen Åsa , Liljeroth Erland , Landschoot Sofie , Ivanović Žarko , Hückelhoven Ralph , Hausladen Hans , Stam Remco
Published: June 2021

Early blight of potato is caused by the fungal pathogen Alternaria solani and is an increasing problem worldwide. The primary strategy to control the disease is applying fungicides such as succinate dehydrogenase inhibitors (SDHI). SDHI-resistant strains, showing reduced sensitivity to treatments, appeared in Germany in 2013, five years after the introduction of SDHIs. Two primary mutations in the Sdh complex (SdhB-H278Y and SdhC-H134R) have been frequently found throughout Europe. How these resistances arose and spread, and whether they are linked to other genomic features, remains unknown.

We performed whole-genome sequencing for A. solani isolates from potato fields across Europe (Germany, Sweden, Belgium, and Serbia) to better understand the pathogen’s genetic diversity in general and understand the development and spread of the genetic mutations that lead to SDHI resistance. We used ancestry analysis and phylogenetics to determine the genetic background of 48 isolates. The isolates can be grouped into 7 genotypes. These genotypes do not show a geographical pattern but appear spread throughout Europe. The Sdh mutations appear in different genetic backgrounds, suggesting they arose independently, and the observed admixtures might indicate a higher adaptive potential in the fungus than previously thought.

Our research gives insights into the genetic diversity of A. solani on a genome level. The mixed occurrence of different genotypes and apparent admixture in the populations indicate higher genomic complexity than anticipated. The conclusion that SDHI tolerance arose multiple times independently has important implications for future fungicide resistance management strategies. These should not solely focus on preventing the spread of isolates between locations but also on limiting population size and the selective pressure posed by fungicides in a given field to avoid the rise of new mutations in other genetic backgrounds.
Analysis of the leaf metabolome in Arabidopsis thaliana mutation accumulation lines reveals association of pleiotropy and fitness consequences
Authors: Kreutzmann Sydney , Pompa Elizabeth , Nguyen Nhan D. , Tilahun Liya , Rutter Matthew T. , Weng Mao-Lun , Fenster Charles B. , Olson-Manning Carrie F.
Published: June 2021

Understanding the mechanisms by which mutations affect fitness and the distribution of mutational effects are central goals in evolutionary biology. Mutation accumulation (MA) lines have long been an important tool for understanding the effect of new mutations on fitness, phenotypic variation, and mutational parameters. However, there is a clear gap in predicting the effect of specific new mutations to their effects on fitness. Here, we complete gene ontology analysis and metabolomics experiments on Arabidopsis thaliana MA lines to determine how spontaneous mutations directly affect global metabolic output in lines that have measured fitness consequences. For these analyses, we compared three lines with relative fitness consistently higher than the unmutated progenitor and three lines with lower relative fitness as measured in four different field trials. In a gene ontology analysis, we find that the high fitness lines were significantly enriched in mutations in or near genes with transcription regulator activity. We also find that although they do not have an average difference in the number of mutations, low fitness lines have significantly more metabolic subpathways disrupted than high fitness lines. Taken together, these results suggest that the effect of a new mutation on fitness depends less on the specific metabolic pathways disrupted and more on the pleiotropic effects of those mutations, and that organisms can explore a considerable amount of physiological space with only a few mutations.

Significance Statement

As the source of all genetic variation, new mutations are crucial for understanding how organisms adapt to their environment. However, the ways in which new mutations affect the range of metabolic reactions that occur in the cell is unknown. With a combination of gene functional analyses and measurement of the small molecules that drive cellular function and physiology, we find that mutations associated with high fitness are disproportionately found in or near proteins-coding genes that regulate the specific timing and location of gene expression and are less disruptive of cellular physiology.
High-throughput screening of aqueous two-phase systems for polyphenol extraction fromA. nodosum: a green chemistry approach
Authors: Olivares-Molina Alex , Parker Brenda
Published: June 2021

Brown macroalgae are an attractive third-generation feedstock of natural products, in order to design green chemistry-compliant processes and reduce the use of organic solvents in bioactive product extraction, aqueous two-phase systems (ATPS) was applied. This research aimed to develop a high-throughput screening (HTS) to recover polyphenols fromAscophyllum nodosumusing ATPS. In total, 384 different 2-phase systems were assessed using an automated liquid-handling system to evaluate polyphenol recovery using a model system of phloroglucinol to establish an optimal 2-phase system for polyphenol partitioning. Various ratios of PEG:potassium phosphate solutions were explored to evaluate partitioning of polyphenols via a scale-down approach. Scale-down selected system showed a recovery of phloroglucinol of 62.9±12.0%, this system was used for scale-up trials. Scale-up studies confirmed that the HTS method was able to recover polyphenols with a 54.8±14.2% in the phloroglucinol model system. When the optimised ATPS system was tested with a polyphenol extract, 93.62±8.24% recovery was observed. When ATPS was applied to a fucoidan and alginate biorefinery residue, 88.40±4.59% polyphenol was recovered. These findings confirm that ATPS is a valuable addition to the bioprocess toolkit for sustainable extraction of natural products from macroalgae in a multiproduct biorefinery approach.

Practical application

Selection of the best concentrations of phase-forming components and recovery conditions for the application of aqueous two-phase systems in an industrial setup has been proved to be laborious and cumbersome. This paper presents an automated platform to rapidly assess several ATPS to recover polyphenols from brown macroalgae and a subsequent confirmation with the scale-up of the potential candidates and contrasted with two case studies. This methodology allows a quick screening for the best aqueous two-phase system and can be expanded to recover high-value products from other types of macroalgae or microalgae.
Systems Genetics of Single Nucleotide Polymorphisms at the Drosophila Obp56h Locus
Authors: Mokashi Sneha S. , Shankar Vijay , Johnstun Joel A. , Huang Wen , Mackay Trudy F. C. , Anholt Robert R. H.
Published: June 2021

Variation in quantitative traits arises from naturally segregating alleles with environmentally sensitive effects, but how individual variants in single genes affect the genotype-phenotype map and molecular phenotypes is not understood. We used CRISPR/Cas9 germline gene editing to generate naturally occurring variants with different site classes and allele frequencies in the Drosophila melanogaster Obp56h gene in a common genetic background. Single base pair changes caused large allele-specific and sexually dimorphic effects on the mean and micro-environmental variance for multiple fitness-related traits and in the Obp56h co-regulated transcriptome. However, these alleles were not associated with quantitative traits in the Drosophila Genetic Reference Panel, suggesting that the small allelic effects observed in genome wide association studies may be an artifact of averaging variable context-dependent allelic effects over multiple genetic backgrounds. Thus, the traditional infinitesimal additive model does not reflect the underlying biology of quantitative traits.
An Efficient Coalescent Epoch Model for Bayesian Phylogenetic Inference
Authors: Bouckaert Remco R.
Published: June 2021

We present a two headed approach called Bayesian Integrated Coalescent Epoch PlotS (BICEPS) for efficient inference of coalescent epoch models. Firstly, we integrate out population size parameters and secondly we introduce a set of more powerful Markov chain Monte Carlo (MCMC) proposals for flexing and stretching trees. Even though population sizes are integrated out and not explicitly sampled through MCMC, we are still able to generate samples from the population size posteriors. This allows demographic reconstruction through time and estimating the timing and magnitude of population bottlenecks and full population histories. Altogether, BICEPS can be considered a more muscular version of the popular Bayesian skyline model.

We demonstrate its power and correctness by a well calibrated simulation study. Furthermore, we demonstrate with an application to SARS-CoV-2 genomic data that some analyses that have trouble converging with the traditional Bayesian skyline prior and standard MCMC proposals can do well with the BICEPS approach.

BICEPS is available as open source package for BEAST 2 under GPL license and has a user friendly graphical user interface. Bayesian phylogenetics, coalescent model, BEAST 2, BICEPS
Using diffusion MRI data acquired with ultra-high gradients to improve tractography in routine-quality data
Authors: Maffei C. , Lee C. , Planich M. , Ramprasad M. , Ravi N. , Trainor D. , Urban Z. , Kim M. , Jones R.J. , Henin A. , Hofmann S.G. , Pizzagalli D.A. , Auerbach R.P. , Gabrieli J.D.E. , Whitfield-Gabrieli S. , Greve D.N. , Haber S.N. , Yendiki A.
Published: June 2021

The development of scanners with ultra-high gradients, spearheaded by the Human Connectome Project, has led to dramatic improvements in the spatial, angular, and diffusion resolution that is feasible for in vivo diffusion MRI acquisitions. The improved quality of the data can be exploited to achieve higher accuracy in the inference of both microstructural and macrostructural anatomy. However, such high-quality data can only be acquired on a handful of Connectom MRI scanners worldwide, while remaining prohibitive in clinical settings because of the constraints imposed by hardware and scanning time. In this study, we first update the classical protocols for tractography-based, manual annotation of major white-matter pathways, to adapt them to the much greater volume and variability of the streamlines that can be produced from today’s state-of-the-art diffusion MRI data. We then use these protocols to annotate 42 major pathways manually in data from a Connectom scanner. Finally, we show that, when we use these manually annotated pathways as training data for global probabilistic tractography with anatomical neighborhood priors, we can perform highly accurate, automated reconstruction of the same pathways in much lower-quality, more widely available diffusion MRI data. The outcomes of this work include both a new, comprehensive atlas of WM pathways from Connectom data, and an updated version of our tractography toolbox, TRActs Constrained by UnderLying Anatomy (TRACULA), which is trained on data from this atlas. Both the atlas and TRACULA are distributed publicly as part of FreeSurfer. We present the first comprehensive comparison of TRACULA to the more conventional, multi-region-of-interest approach to automated tractography, and the first demonstration of training TRACULA on high-quality, Connectom data to benefit studies that use more modest acquisition protocols.
Comprehensive analysis of full-length transcripts reveal aberrations of splicing variants in liver cancer
Authors: Kiyose Hiroki , Nakagawa Hidewaki , Ono Atsushi , Aikata Hiroshi , Ueno Masaki , Hayami Shinya , Yamaue Hiroki , Chayama Kazuaki , Shimada Mihoko , Wong Jing Hao , Fujimoto Akihiro
Published: June 2021

Genes generate various transcripts by alternative splicing, and these transcripts can have diverse functions. However, in most transcriptome studies, short-reads sequencing technologies (next-generation sequencers) have been used and full-length transcripts have not been observed directly. Although long-reads sequencing technologies would enable us to sequence full-length transcripts, analysis of the data is a difficult task. In the present study, we developed an analysis pipeline named SPLICE to analyze full-length cDNA sequences. Using this method, we analyzed cDNA sequences from 42 pairs of hepatocellular carcinoma (HCC) and matched non-cancerous liver with Oxford Nanopore technology. Our analysis detected 46,663 transcripts from the protein-coding genes in the HCCs and the matched non-cancerous livers, of which 5,366 (11.5 %) were novel. Comparison of expression levels identified 9,933 differentially expressed transcripts (DETs) in 4,744 genes. Importantly, 746 genes with DET were not found by the gene-level analysis. We also identified novel exons derived from transposable elements (TEs). In the analysis of transcripts from hepatitis B virus (HBV), HBx-human TE fusions were found to be overexpressed in the HCCs. Furthermore, fusion gene detection showed novel recurrent fusion events. These results suggest that long-reads sequencing technologies allow us to analyze full-length transcripts, and show the importance of splicing variants in carcinogenesis.
Information redundancy across spatial scales modulates early visual cortical processing
Authors: Petras Kirsten , ten Oever Sanne , Dalal Sarang S. , Goffaux Valerie
Published: June 2021

Visual images contain redundant information across spatial scales where low spatial frequency contrast is informative towards the location and likely content of high spatial frequency detail. Previous research suggests that the visual system makes use of those redundancies to facilitate efficient processing. In this framework, a fast, initial analysis of low-spatial frequency (LSF) information guides the slower and later processing of high spatial frequency (HSF) detail. Here, we used multivariate classification as well as time-frequency analysis of MEG responses to the viewing of intact and phase scrambled images of human faces to demonstrate that the availability of redundant LSF information, as found in broadband intact images, correlates with a reduction in HSF representational dominance in both early and higher-level visual areas as well as a reduction of gamma-band power in early visual cortex. Our results indicate that the cross spatial frequency information redundancy that can be found in all natural images might be a driving factor in the efficient integration of fine image details.