bluuebunny/crossref_metadata_2025 huggingface dataset:
A Berger-linear Buildup Approximation for Air
Authors: Overcamp Thomas J.
Published: November 2021

A combination of the Berger and the linear buildup approximations with the assumption of conservation of energy was fitted for air. The values predicted by this Berger-linear buildup approximation were generally more accurate than those predicted by the Berger approximation alone. Although it is not as accurate as the geometric-progression approximation, the Berger-linear approximation is analytically simpler and makes it easier to find analytical solutions for point source kernel shielding calculations.
Postoperative blood pressure management in patients treated in the ICU after noncardiac surgery
Authors: Briesenick Luisa , Flick Moritz , Saugel Bernd
Published: November 2021

Purpose of review

Blood pressure management is a cornerstone of hemodynamic management in patients treated in the ICU after noncardiac surgery. Postoperative blood pressure management is challenging, because blood pressure alterations after surgery can be profound and have numerous causes.

Recent findings

Postoperative blood pressure alterations are common in patients treated in ICUs after noncardiac surgery. There is increasing evidence that hypotension during the initial days after noncardiac surgery is associated with postoperative adverse outcomes including myocardial infarction and death, acute myocardial injury, acute kidney injury, major adverse cardiac or cerebrovascular events, and delirium. Thus, postoperative hypotension could be a modifiable risk factor for postoperative adverse outcomes. However, robust evidence for a causal relationship between postoperative blood pressure and postoperative adverse outcomes is still lacking.

Future research on postoperative blood pressure management in patients treated in the ICU after noncardiac surgery needs to assess whether the prevention or treatment of postoperative blood pressure alterations – especially postoperative hypotension – reduces the incidence of postoperative adverse outcomes.
Associations between the serum magnesium and all-cause or cardiovascular mortality in chronic kidney disease and end-stage renal disease patients
Authors: Liu Hongyan , Wang Rui
Published: November 2021

Background:

Some studies have found that hypomagnesemia is associated with vascular calcification, atherosclerosis, and cardiovascular disease, which may lead to increased mortality in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) who need to maintain hemodialysis (HD). However, the conclusion of these studies remain controversial.

Methods:

Relevant literature was retrieved from the database of Cochrane library, PubMed, EMBASE, and CNKI until December 2020, without any language restrictions. The data was analyzed using the Stata 12.0 software.

Results:

A total of 31 studies were included, involving 205436 participants. The results showed that after multivariable adjusted, hypomagnesemia was significant associated with the risk of all-cause mortality in patients with CKD and end-stage renal disease (ESRD) (hazard ratios [HR] 1.955; 95% confidence interval (95% CI) 1.511-2.528; P = .000; hypomagnesemia vs normal magnesium or hypermagnesemia). In contrast, in patients with CKD and ESRD, hypermagnesemia was negatively correlated with all-cause mortality (HR 0.873; 95% CI 0.793-0.960; P = .005) (per unit increase). Moreover, in the adjusted model, it was observed that hypermagnesemia was significantly associated with a reduced risk of cardiovascular death (HR 0.598; 95% CI 0.094-1.102, P = .020). In addition, subgroup analysis found that hypomagnesemia was closely related to the increase of all-cause mortality in HD patients (HR 1.799; 95% CI 1.375-2.354; P = .000) (hypomagnesemia vs normal magnesium or hypermagnesemia).

Conclusion:

Our results show that hypomagnesemia is significantly associated with cardiovascular and all-cause mortality in maintenance HD patients. Further studies should be conducted to evaluate the benefits of magnesium correction in maintenance dialysis patients with hypomagnesemia.
An elderly advanced non-small cell lung cancer patient harboring rare epidermal growth factor receptor mutations L861R benefited from afatinib
Authors: Qu Fanjie , Wu Shuang , Dong Huacheng , Yan Xin
Published: November 2021

Rationale:

Tyrosine kinase inhibitors (TKIs) have significant efficacy in patients with advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations. No clear evidence exists that EGFR-L861R is sensitive to TKIs, and the best treatment for NSCLC patients with EGFR-L861R mutation is undetermined.

Patient concerns:

We report the characteristics, efficacy, and adverse events of a patient harboring rare EGFR mutations L861R treated with afatinib, and summarize the currently available evidence and ongoing clinical trials regarding it.

Diagnosis:

The patient was diagnosed with advanced lung cancer that had progressed after previous osimertinib drug therapy, based on the clinical course and imaging findings.

Interventions:

The patient underwent genetic testing, and next-generation sequencing detected rare EGFR mutations L861R in the plasma (mutation abundance 8.1%). The patient was then administered afatinib at 30 mg quaque die combined with bevacizumab at 300 mg every 2 weeks.

Outcomes:

After 1 month of treatment, the patient achieved a quick response, and symptoms improved significantly. Repeat evaluation imaging demonstrated that the lesions in the lung and brain were significantly smaller and evaluation showed partial remission. However, despite showing an initial response, the patient presented with behavioral abnormalities, headaches, and sudden confusion after 2 months, and subsequently appeared coma. The family elected to forgo further therapy due to the patient's age and enrolled in hospice care, passing 14 months after the initial diagnosis.

Lesson:

EGFR-L861R mutation could help predict the sensitivity of patients with advanced NSCLC to TKIs.
The effect of operating room nursing intervention on the psychological status and incidence of emergence agitation in the recovery period of general anesthesia
Authors: Zhu Hongying , Cheng Liurong , Tang Ting , Ke Yajuan , Wu Duozhi , Huang Yi
Published: November 2021

Background:

During the recovery period of general anesthesia, patients are disturbed by residual anesthetic drugs, manifesting as clinical signs of confusion, drowsiness and disorientation, and even abnormal psychology and limb agitation at varying degrees in severe cases. These stress reactions are detrimental to the postoperative recovery, which can be life-threatening. Operating room nursing intervention (ORNI) is a novel nursing model that prevents stress reactions during the recovery period of general anesthesia. However, whether ORNI can improve the psychological condition and reduce the incidence of emergence agitation in the recovery period of general anesthesia remains controversial. Therefore, this study aims to evaluate the effect of ORNI on the psychological status and incidence of emergence agitation in the recovery period of general anesthesia through a systematic review and meta-analysis, thus providing clinical evidence to support it.

Methods:

Randomized controlled trials reporting the effect of ORNI on the recovery period of general anesthesia published before October 2021 will be searched in the Chinese Scientific Journal Database, China National Knowledge Infrastructure Database, Wanfang, China Biomedical Literature Database, PubMed, Embase, the Cochrane Library, and Web of Science. Eligible literatures will be screened out according to inclusion and exclusion criteria, and their quality will be assessed using the Cochrane Risk of Bias Assessment Tool. Meta-analysis will be performed using Revman 5.4 software.

Results:

This study will evaluate the effect of the ORNI on the recovery period of general anesthesia by calculating the incidence of emergence agitation, and grading the self-rating anxiety scale and self-rating depression scale scores.

Conclusion:

This study will provide a reliable evidence-based basis for the application of ORNI in the recovery period of general anesthesia.

OSF Registration number:

DOI 10.17605/OSF.IO/P3A4T.
A case report of cryoablation and electrochemotherapy in kidney cancer
Authors: Mastrandrea Giovanni , Laface Carmelo , Fazio Vito , Lopetuso Marco , Falagario Gianmarco , Molinari Pasquale , Ranieri Girolamo , Gadaleta Cosmo Damiano
Published: November 2021

Rationale:

According to scientific literature, cryoablation (CA) and electrochemotherapy (ECT) have been used for the treatment of small renal masses. However, no data have been published regarding the combination of these techniques as therapy of primary kidney cancers. Therefore, we report the case of an old woman affected by localized kidney cancer and discuss the potential therapeutic application of CA combined with subsequent deep ECT in this setting.

Patient concerns:

An 85 years-old-woman was evaluated because of a localized kidney cancer. Her background history included long-time hypertension and diabetes mellitus in drug treatment.

Diagnoses:

In February 2018, the follow-up contrast enhancement computed tomography (ceCT) documented a suspected 18×10 mm metastasis at the lower right lobe of the lung. The ceCT also showed a suspected primary malignancy of 25×18 mm at right kidney.

Interventions:

The kidney cancer was treated with a two-phase procedure: percutaneous CA and subsequent deep ECT.

Outcomes:

Patient obtained a complete response according to modified Response Evaluation Criteria in Solid Tumors, without renal function or quality of life impairment. No procedure-related complications were observed. Moreover, a shorter period of hospitalization and convalescence were needed respect to standard surgery. No sign of relapse was observed during follow-up period.

Lessons:

This combined strategy proved to be safe and effective. Moreover, the application of these blended loco-regional techniques showed several other advantages such as reduced hospitalization and a shorter period of convalescence respect to standard surgery.
CYP1A2 polymorphism may contribute to agomelatine-induced acute liver injury
Authors: Wang Shushan , Xu Qing , Qu Kankan , Wang Jun , Zhou Zhenhe
Published: November 2021

Rationale:

Liver function monitoring is recommended when agomelatine is prescribed, although liver enzymes are not considered predictive biomarkers. Most patients present with acute liver injury, with only a few presenting with levels of liver enzymes that are over 30 times the upper limit of normal. The patient-specific risk factors that are associated with liver injury remain unclear. Thus, this report provides new insights into the mechanism of agomelatine-induced acute hepatocellular injury based on cytochrome P450 family 1 subfamily A member 2 (CYP1A2) polymorphism.

Patient concerns:

We present a case of acute hepatocellular injury in a 75-year-old man who was taking agomelatine at a dose of 50 mg/qn. All hepatitis virus test results were negative. No history of liver disease was observed. As CYP1A2 is the main metabolic enzyme of agomelatine, CYP1A2 AA (rs762551) genetic polymorphism was analyzed.

Diagnosis:

The patient's transaminases level exceeded the critical value on day 72 after starting oral agomelatine.

Interventions:

The patient received intravenous magnesium isoglycyrrhizinate, a liver cell-protecting agent, followed by the withdrawal of agomelatine.

Outcomes:

There was an improvement in the levels of the liver enzymes and no subsequent organ dysfunction was observed.

Lessons:

Here, we report a case of acute hepatocellular injury characterized by a very high aspartate aminotransferase level. Periodic liver function testing throughout the treatment period can help in the rapid and appropriate diagnosis of acute liver injury, particularly in the absence of typical clinical manifestations. Agomelatine hepatic toxicity might be related to an idiosyncratic metabolic reaction that depends on individual patient differences. As it is the main metabolic enzyme of agomelatine, CYP1A2 genetic polymorphism may contribute to liver injury by affecting its metabolites.
Effects of attentional bias modification on chronic low back pain in older outpatients
Authors: Hasegawa Takashi , Nishi Keita , Nakashima Akira , Moriuchi Takefumi , Iso Naoki , Koseki Hironobu , Tabira Takayuki , Higashi Toshio
Published: November 2021

Objectives:

In the present study, the effect of attentional bias modification (ABM) on older outpatients, with chronic low back pain, was examined.

Design:

This was a single-center, randomized, single-blinded, crossover trial and patients were randomly divided in a 1:1 allocation ratio into two groups: an ABM Leading group and an ABM Trailing group.

Participants:

Forty-three outpatients with chronic low back pain participated.

Interventions:

Patients were evaluated four times and the treatments were ABM + Normal intervention or Normal intervention only.

Outcomes:

Outcome measures included pain intensity on the Numerical Rating Scale, the Pain Catastrophizing Scale, Fear-Avoidance Beliefs Questionnaire, Hospital Anxiety and Depression Scale, Somatic Symptom Scale-8, and EuroQol 5 Dimension-3 levels questionnaire. In addition, we performed the 30-second Chair-Stand test and the Timed Up & Go test for physical function evaluations.

Results:

There was no change in pain intensity due to ABM. However, the total Pain Catastrophizing Scale score was significantly decreased, and the EuroQol 5 Dimension-3 levels questionnaire and 30-second chair-stand test were significantly improved (P <.05).

Trial registration:

The Health Science Ethics Committee, Graduate School of Biomedical Sciences, Nagasaki University (permit number: 17060861), and the clinical trial was registered with UMIN (UMIN000029424).
Pooled analysis of the efficacy and safety of tibial nerve stimulation versus antimuscarinic agents in the management of overactive bladder syndrome
Authors: Xia Liping , Yan Huilei , Sun Yalei , Zhu Yan , Wu Yudong , Chen Zhipeng , Su Shunye
Published: November 2021

Objectives:

The purpose of this meta-analysis was to evaluate the efficacy and safety of tibial nerve stimulation (TNS) versus antimuscarinic agents in the management of overactive bladder (OAB) syndrome.

Methods:

The databases MEDLINE, EMBASE, the Cochrane Controlled Trial Register of Controlled Trials from 2000 to May 2021 were searched to identify randomized controlled trials that referred to the use of TNS and antimuscarinic agents for the treatment of OAB syndrome. A systematic review and meta-analysis was conducted.

Results:

Eight publications involving 420 patients were included in the meta-analysis. In the analysis, we found TNS had a comparable effect with antimuscarinic agents on micturition per day, nocturia, urge incontinence, and voided volume (P = .9; .4; .78; .44, respectively). Scores measured by questionnaires Overactive Bladder Symptom Score and Overactive Bladder questionnaire Short Form items also indicated no statistical difference between 2 groups. TNS group had a significantly less discontinuation rate and adverse events (P = .003; .0001).

Conclusions:

TNS is as effective as antimuscarinic agents for the treatment of OAB. Moreover, TNS appears to be more tolerable and safer than antimuscarinic agents.
Whole-exome sequencing of a novel initiation codon mutation in RUNX2 in a Chinese family with cleidocranial dysplasia
Authors: Yang Liyuan , Lu Genqi , Shen Wenjing , Chen Wenjing , Lu Haiyan , Zhang Guozhong , Yuan Shuo , Zheng Shushen , Ren Jiabao
Published: November 2021

Cleidocranial dysplasia (CCD) is mainly attributable to a variant of runt-related transcription factor 2 (RUNX2) on chromosome 6p21. CCD is an autosomal dominant skeletal disorder characterized by open/delayed closure of fontanels, clavicular hypoplasia, retention of deciduous teeth, and supernumerary permanent teeth. The aim of this study was to investigate potentially pathogenic mutations in 2 Chinese families. Genomic DNA was obtained from peripheral blood lymphocytes, and whole exome sequencing and Sanger sequencing were performed to detect gene variants. Real-time quantitative PCR was performed to determine the mRNA expression level of RUNX2 in the proband of family 1. Silico algorithms and conservation analyses were used to evaluate the functional impact. We identified a novel initiation codon mutation (c.2T>C) and a previously reported mutation (c.569G>A). Familial co-segregation verified an autosomal-dominant inheritance pattern. Our findings demonstrated that the novel mutation c.2T>C causes CCD. Quantitative real-time PCR suggested that downregulated RUNX2 levels and haploinsufficiency in RUNX2 lead to CCD. These results extend the spectrum of RUNX2 mutations in CCD patients and can be used for genetic consultation and prenatal diagnosis.
Lentilactobacillus kosonis sp. nov., isolated from kôso, a Japanese sugar-vegetable fermented beverage
Authors: Chiou Tai-Ying , Suda Wataru , Oshima Kenshiro , Hattori Masahira , Matsuzaki Chiaki , Yamamoto Kenji , Takahashi Tomoya
Published: November 2021

A novel lactic acid-producing, Gram-stain-positive, catalase-negative and rod-shaped strain, designated as strain C06_No.73T, was isolated from a traditional Japanese fermented beverage called kôso. According to the results of phylogenetic analysis based on 16S rRNA gene sequences, strain C06_No.73T belongs to the genus

Lentilactobacillus

. The closest type strain was

Lentilactobacillus curieae

CCTCC M 2011381T, with a sequence identity of 98.1 %. The identity values with other strains were all below 97 %. The isolate propagated under the conditions of 18–39 °C (optimum, 27 °C for 48 h incubation) and pH 4.0–7.0 (optimum, pH 6.5). The G+C content of its genomic DNA was determined to be 37.9 mol%. The main fatty acids were C16 : 0, C18 : 1 ω7c, C18 : 1 ω9c and C19 : 0 cyclopropane 11,12. The major polar lipid was identified as phosphatidylglycerol. No isoprenoid quinone was detected. The predominant cell-wall amino acids were lysine, alanine, glutamic acid and aspartic acid. Neither meso-diaminopimelic acid nor ornithine were detected. On the basis of this polyphasic taxonomic study, the isolate is concluded to represent a novel species, for which the name Lentilactobacillus kosonis sp. nov. is proposed. The type strain is C06_No.73T (=NBRC 111893T=BCRC 81282T).
Effects of drinking water, sanitation, handwashing, and nutritional interventions on immune status in young children: a cluster-randomized controlled trial in rural Bangladesh
Authors: Lin Audrie , Mertens Andrew N. , Tan Sophia , Rahman Md. Ziaur , Hester Lisa , Kim Lisa , Arnold Benjamin F. , Karim Md. Rabiul , Shahriar Sunny , Ali Shahjahan , Shoab Abul K. , Hossen Md. Saheen , Mutsuddi Palash , Famida Syeda Luthfa , Akther Salma , Rahman Mahbubur , Unicomb Leanne , Butzin-Dozier Zachary , Hemlock Caitlin , Hubbard Alan E. , Stewart Christine P. , Fernald Lia C. H. , Colford John M. , Luby Stephen P. , Dhabhar Firdaus S.
Published: November 2021

While studies have speculated that immune function may play a role in how water, sanitation, hygiene, and nutritional (N+WSH) interventions may individually impact child growth and development, the combined effects of these interventions on immune system development are unknown. Here, we report on a trial in rural Bangladesh, where we cluster-randomized pregnant women into control and N+WSH arms. Among the birth cohort, we quantified plasma IL-1β, IL-6, TNF-α, IL-2, IL-12p70, IFN-γ, IL-4, IL-5, IL-13, IL-17A, IL-21, IL-10, and GM-CSF at ages 14 and 28 months. Cytokine ratios were included as prespecified outcomes to examine the net inflammatory environment. We assessed 704 children. After one year, TNF-α/IL-10, IL-12/IL-10, and IL-17A/IL-10 ratios were lower in the intervention group compared to the control group (mean difference: -0.12 to -0.19, p<0.05), indicating the intervention promoted IL-10 driven immunoregulation. Similar reductions in ratios of pro-inflammatory cytokines to IL-10 were sustained in the intervention group after two years. After one year, IL-12/IL-4, IL-12/IL-5, IFN-γ/IL-5, and IL-12/IL-13 ratios were lower in the intervention group (−0.18 to -0.27, p<0.05), suggesting a shift towards a Th2 cytokine response. These findings suggest that the N+WSH intervention enhanced the immunoprotective and immunoregulatory responses, and suppressed/counteracted the inflammatory/immunopathological response, of the immune triad.
Sequence learning attenuates cortical responses in both frontal and perceptual cortices in early infancy
Authors: Jaffe-Dax Sagi , Herbolzheimer Anna , Bejjanki Vikranth Rao , Emberson Lauren L.
Published: November 2021

Prior work has found that the frontal lobe is involved in higher-order sequential and statistical learning in young infants. Separate lines of work have found evidence of modulation of posterior sensory cortices during and after learning tasks. How do these processes relate? Here, we build evidence the infant frontal lobe was modulated during sequential learning and ask whether posterior perceptual cortices show corresponding modulation. First, replicating and extending past work, we found evidence of frontal lobe involvement in this task. Second, consistent with our hypotheses, we found that there is a corresponding attenuation of neural responses in the posterior perceptual cortices (temporal and occipital) to predictable compared to unpredictable audiovisual sequences. This study provides convergent evidence that the frontal lobe is crucial for higher-level learning in young infants but that it likely works as part of a large, distributed network of regions to modulate infant neural responses during learning. Overall, this work challenges the view that the infant brain is not dynamic and disconnected, lacking in long-range neural connections. Instead, this paper reveals patterns of a highly dynamic and interconnected infant brain that change rapidly as a result of new, learnable experiences.
RPRM negatively regulates ATM levels involving its phosphorylation mediated by CDK4/CDK6
Authors: Zhang Yarui , Ou Guomin , Ye Zhujing , Zhou Zhou , Cao Qianlin , Li Mengting , Wang Jingdong , Cao Jianping , Yang Hongying
Published: November 2021

Sensitizing cancer cells to radio- and chemotherapy remains a hot topic in cancer treatment. Here it is identified that Protein Reprimo (RPRM) negatively regulates the levels of ataxia-telangiectasia mutated (ATM) protein kinase, a master regulator of DNA damage response (DDR) in the presence of DNA double-strand breaks (DSBs), resulting in impaired DNA repair efficiency and enhanced cellular sensitivity to genotoxic agents. Mechanistically, although RPRM is primarily located in cytoplasm, it rapidly translocates to nucleus shortly after induced by X-irradiation, interacts with ATM and promotes the nuclear export and proteasomal degradation of ATM. The nuclear translocation of RPRM is associated with its phosphorylation at serine 98, which is mediated by cyclin-dependent kinases 4/6 (CDK4/6). Inhibition of CDK4/6 stabilizes RPRM and promotes its nuclear import, in turn enhances the nuclear export of ATM and the reduction of ATM levels. As a result, RPRM overexpression and its phosphorylation inhibition sensitize cells to genotoxic agents. Moreover, RPRM deficiency significantly increases resistance to radiation-induced damage both in vitro and in vivo. These findings establish a crucial regulatory mechanism in which ATM is negatively modulated by RPRM, suggesting that RPRM may serve as a novel target for both cancer therapy and radiation protection.
Using high-resolution contact networks to evaluate SARS-CoV-2 transmission and control in large-scale multi-day events
Authors: Pung Rachael , Firth Josh A , Spurgin Lewis G ,   Singapore CruiseSafe working group,   CMMID COVID-19 working group, Lee Vernon J , Kucharski Adam J
Published: November 2021

The emergence of the highly transmissible SARS-CoV-2 Delta variant has created a need to reassess the risk posed by increasing social contacts as countries resume pre-pandemic activities, particularly in the context of resuming large-scale events over multiple days. To examine how social contacts formed in different activity settings influences interventions required to control outbreaks, we combined high-resolution data on contacts among passengers and crew on cruise ships with network transmission models. We found passengers had a median of 20 (IQR 10–36) unique close contacts per day, and over 60% of their contact episodes were made in dining or sports areas where mask wearing is typically limited. In simulated outbreaks, we found that vaccination coverage and rapid antigen tests had a larger effect than mask mandates alone, indicating the importance of combined interventions against Delta to reduce event risk in the vaccine era.
Multi-ethnic polygenic risk modifies the association between APOL1 high risk genotypes and chronic kidney disease
Authors: Vy Ha My T. , Gulamali Faris F. , Glicksberg Benjamin S , Gutierrez Orlando , Cooper Richard , Bottinger Erwin P , Cho Judy , Loos Ruth J.F. , Horowitz Carol R. , Do Ron , Nadkarni Girish N
Published: November 2021

The burden of advanced chronic kidney disease (CKD) falls disproportionately on minorities including African Americans (AAs) and Hispanic Americans (HAs) with admixed ancestry. Even though APOL1 high-risk genotypes increase risk of kidney disease, their penetrance is incomplete, indicating that the modification of APOL1 high risk may be polygenic. For this study, we used three multi-ethnic cohorts with APOL1 high risk genotypes and calculated a multi-ethnic PRS using publicly available summary statistics. We show that CKD risk is significantly modified by a multi-ethnic polygenic risk score. Standardizing population screening for CKD by including APOL1 high-risk genotypes and polygenic risk score may improve risk stratification and outcomes.
Repressing PTBP1 is incapable to convert reactive astrocytes to dopaminergic neurons in a mouse model of Parkinson’s disease
Authors: Chen Weizhao , Zheng Qiongping , Huang Qiaoying , Ma Shanshan , Li Mingtao
Published: November 2021

Lineage reprograming of resident glia cells to induced dopaminergic neurons (iDAns) holds attractive prospect for cell-replacement therapy of Parkinson’s disease (PD). Recently, whether repressing polypyrimidine tract binding protein 1 (PTBP1) could truly achieve efficient astrocyte-to-iDAn conversion in substantia nigra and striatum aroused widespread controversy. Although reporter positive iDAns were observed by two groups after delivering adeno-associated virus (AAV) expressing a reporter with shRNA or Crispr-CasRx to repress astroglial PTBP1, the possibility of AAV leaking into endogenous DAns could not be excluded without using a reliable lineage tracing method. By adopting stringent lineage tracing strategy, two other studies showed that neither knockdown nor genetic deletion of quiescent astroglial PTBP1 fails to obtain iDAns under physiological condition. However, the role of reactive astrocyte might be underestimated since upon brain injury, reactive astrocyte could acquire certain stem cell hallmarks which may facilitate the lineage conversion process. Therefore, whether reactive astrocytes could be genuinely converted to DAns after PTBP1 repression in a PD model needs further validation. In this study, we used Aldh1l1-CreERT2-mediated specific astrocyte-lineage tracing method to investigate whether reactive astrocytes could be converted to DAns in the 6-OHDA PD model. However, we found that no astrocyte-originated DAn was generated after effective knockdown of astroglial PTBP1 either in the substantia nigra or in the striatum, while AAV “leakage” to nearby neurons was observed. Our results further confirmed that repressing PTBP1 is unable to convert astrocytes to DAns no matter in physiological or PD-related pathological conditions.

Graphic abstract

Highlights

AAV-shPtbp1 rapidly and efficiently induces viral-reporter-labeled DAns in mouse brain under physiological condition

Viral-reporter-positive DAns are not originated from PTBP1 repressed and lineage traced reactive astrocytes in a mouse PD model
Batch-Mask: An automated Mask R-CNN workflow to isolate non-standard biological specimens for color pattern analysis
Authors: Curlis John David , Renney Timothy , Davis Rabosky Alison R. , Moore Talia Y.
Published: November 2021

Efficient comparisons of biological color patterns are critical for understanding the mechanisms by which organisms evolve in ecosystems, including sexual selection, predator-prey interactions, and thermoregulation. However, elongate or spiral-shaped organisms do not conform to the standard orientation and photographic techniques required for automated analysis. Currently, large-scale color analysis of elongate animals requires time-consuming manual landmarking, which reduces their representation in coloration research despite their ecological importance.

We present Batch-Mask: an automated and customizable workflow to facilitate the analysis of large photographic data sets of non-standard biological subjects. First, we present a user guide to run an open-source region-based convolutional neural network with fine-tuned weights for identifying and isolating a biological subject from a background (masking). Then, we demonstrate how to combine masking with existing manual visual analysis tools into a single streamlined, automated workflow for comparing color patterns across images.

Batch-Mask was 60x faster than manual landmarking, produced masks that correctly identified 96% of all snake pixels, and produced pattern energy results that were not significantly different from the manually landmarked data set.

The fine-tuned weights for the masking neural network, user guide, and automated workflow substantially decrease the amount of time and attention required to quantitatively analyze non-standard biological subjects. By using these tools, biologists will be able to compare color, pattern, and shape differences in large data sets that include significant morphological variation in elongate body forms. This advance will be especially valuable for comparative analyses of natural history collections, and through automation can greatly expand the scale of space, time, or taxonomic breadth across which color variation can be quantitatively examined.
Mapping of individual sensory nerve axons from digits to spinal cord with the Transparent Embedding Solvent System
Authors: Yi Yating , Men Yi , Zhang Shiwen , Wang Yuhong , Chen Zexi , Lachika Ed , Peng Hanchuan , Ge Woo-Ping , Zhao Hu
Published: November 2021

Understanding the connections and projections of neurons has been a fundamental issue for neuroscience. Although strategies have been developed to map the projection of individual axons within the mouse brain, high resolution mapping of individual peripheral nerve axons in peripheral organs or spinal cord has never been achieved. Here, we designed the Transparent Embedding Solvent System (TESOS) method and developed a technical pipeline for imaging, reconstructing and analyzing large samples containing various tissue types at sub-micron resolution. The mouse whole body was reconstructed at micron-scale resolution. We were able to image, reconstruct and analyze the complete axonal projection of individual sensory neurons within an intact mouse paw or spinal cord at sub-micron resolution. Furtherly, we imaged and reconstructed the entire projection course of individual sensory neurons from adult mouse digits to the spinal cord. The TESOS method provides an efficient tool for micron-scale connectome mapping of the peripheral nervous system.
Multi-Branch-CNN: classification of ion channel interacting peptides using parallel convolutional neural networks
Authors: Yan Jielu , Zhang Bob , Zhou Mingliang , Kwok Hang Fai , Siu Shirley W. I.
Published: November 2021

Ligand peptides that have high affinity for ion channels are critical for regulating ion flux across the plasma membrane. These peptides are now being considered as potential drug candidates for many diseases, such as cardiovascular disease and cancers. There are several studies to identify ion channel interacting peptides computationally, but, to the best of our knowledge, none of them published available tools for prediction. To provide a solution, we present Multi-branch-CNN, a parallel convolutional neural networks (CNNs) method for identifying three types of ion channel peptide binders (sodium, potassium, and calcium). Our experiment shows that the Multi-Branch-CNN method performs comparably to thirteen traditional ML algorithms (TML13) on the test sets of three ion channels. To evaluate the predictive power of our method with respect to novel sequences, as is the case in real-world applications, we created an additional test set for each ion channel, called the novel-test set, which has little or no similarities to the sequences in either the sequences of the train set or the test set. In the novel-test experiment, Multi-Branch-CNN performs significantly better than TML13, showing an improvement in accuracy of 6%, 14%, and 15% for sodium, potassium, and calcium channels, respectively. We confirmed the effectiveness of Multi-Branch-CNN by comparing it to the standard CNN method with one input branch (Single-Branch-CNN) and an ensemble method (TML13-Stack). To facilitate applications, the data sets, script files to reproduce the experiments, and the final predictive models are freely available athttps://github.com/jieluyan/Multi-Branch-CNN.
Pathological characteristics of pulmonary toxicity in F344 rats exposed by inhalation to cross-linked water-soluble acrylic acid polymers
Authors: Yamano Shotaro , Takeda Tomoki , Goto Yuko , Hirai Shigeyuki , Furukawa Yusuke , Kikuchi Yoshinori , Misumi Kyohei , Suzuki Masaaki , Takanobu Kenji , Senoh Hideki , Saito Misae , Kondo Hitomi , Kobashi Yoichiro , Okamoto Kenzo , Kishimoto Takumi , Umeda Yumi
Published: November 2021

Background

Recently in Japan, six workers at a chemical plant that manufactures resins developed interstitial lung diseases after being involved in loading and packing cross-linked water-soluble acrylic acid polymers (CWAAPs). Since CWAAPs are not on the list of occupational diseases, the present study examined the lung damage potential of two CWAAPs (CWAAP-A and CWAAP-B) in rats, investigated pathological mechanisms, and established a method to rapidly evaluate the harmfulness of CWAAPs.

Methods

Using a whole-body inhalation exposure system, male F344 rats were exposed once to 40 or 100 mg/m3 of CWAAP-A for 4 hours or to 15 or 40 mg/m3 of CWAAP-A for 4 hours per day once per week for 2 months (a total of 9 exposures). In a separate set of experiments, male F344 rats were administered 1 mg/kg CWAAP-A or CWAAP-B by intratracheal instillation once every two weeks for 2 months (a total of five doses). Lung tissues, mediastinal lymph nodes, and bronchoalveolar lavage fluid were collected and subjected to biological and histopathological analyses.

Results

A single 4-hour exposure to CWAAP caused alveolar injury, and repeated exposures resulted in regenerative changes in the alveolar epithelium with activation of TGFβ signaling. During the recovery period after the last exposure, some alveolar lesions were partially healed, but other lesions developed into alveolitis with fibrous thickening of the alveolar septum. Rats administered CWAAP-A by intratracheal instillation developed qualitatively similar pulmonary pathology as rats exposed to CWAAP-A by inhalation. At 2 weeks after intratracheal instillation, rats administered CWAAP-B appeared to have a slightly higher degree of lung lesions compared to rats administered CWAAP-A, however, there was no difference in these lesions of CWAAP-A and CWAAP-B in rats examined 18 weeks after administration of these materials.

Conclusions

The present study provides evidence of rat lung pathogenesis after inhalation exposure to CWAAP-A. This study also demonstrates that the lung pathology of rats exposed to CWAAP-A by systemic inhalation was qualitatively similar to that of rats administered CWAAP-A by intratracheal instillation. The use of intratracheal instillation as an adjunct to systemic inhalation is expected to significantly accelerate the risk assessment for a variety of CWAAPs.
Polymer skulls with integrated transparent electrode arrays for cortex-wide opto-electrophysiological recordings
Authors: Donaldson Preston D. , Navabi Zahra S. , Carter Russell E. , Fausner Skylar M. L. , Ghanbari Leila , Ebner Timothy J. , Swisher Sarah L. , Kodandaramaiah Suhasa B.
Published: November 2021

Electrophysiological and optical imaging provide complementary neural sensing capabilities – electrophysiological recordings have the highest temporal resolution, while optical imaging allows recording the activities of genetically defined populations at high spatial resolution. Combining these complementary, yet orthogonal modalities to perform simultaneous large-scale, multimodal sensing of neural activity across multiple brain regions would be very powerful. Here we show that transparent, inkjet-printed electrocorticography (ECoG) electrode arrays can be seamlessly integrated with morphologically conformant transparent polymer skulls for multimodal recordings across the cortex. These ‘eSee-Shells’ were implanted on transgenic mice expressing the Ca2+indicator GCaMP6f in cortical excitatory cells and provided a robust opto-electrophysiological interface for over 100 days. eSee-Shells enable simultaneous mesoscale Ca2+imaging and ECoG acquisition under anesthesia as well as in awake animals presented with sensory stimuli. eSee-Shells further show sufficient clarity and transparency to observe single-cell Ca2+signals directly below the electrodes and interconnects. Simultaneous multimodal measurement of cortical dynamics reveals changes in both ECoG and Ca2+signals that depend on the behavioral state.
The impact of rare germline variants on human somatic mutation processes
Authors: Pour Mischan Vali , Lehner Ben , Supek Fran
Published: November 2021

Somatic mutations are an inevitable component of ageing and the most important cause of cancer. The rates and types of somatic mutation vary across individuals, but relatively few inherited influences on mutation processes are known. We performed a comprehensive gene-based rare variant association study with diverse mutational processes, using human cancer genomes from over 11,000 individuals of European ancestry. By combining burden and variance tests, we identify 207 associations involving 15 somatic mutational phenotypes and 42 genes that replicated in an independent data set at a FDR of 1%. We associated rare inherited deleterious variants in novel genes such asMSH3,EXO1,SETD2, andMTORwith two different forms of DNA mismatch repair deficiency, and variants in genes such asEXO1,PAXIP1, andWRNwith deficiency in homologous recombination repair. In addition, we identified associations with other mutational processes, such asAPEX1with APOBEC-signature mutagenesis. Many of the novel genes interact with each other and with known mutator genes within cellular sub-networks. Considered collectively, damaging variants in the newly-identified genes are prevalent in the population. We suggest that rare germline variation in diverse genes commonly impacts mutational processes in somatic cells.
CXCR4+ Treg cells control serum IgM levels and natural IgM autoantibody production by B1 cells in the bone marrow
Authors: Elias Shlomo , Sharma Rahul , Schizas Michael , Valdez Izabella , Park Sun-Mi , Gonzalez-Figueroa Paula , Li Quan-Zhen , Hoyos Beatrice , Rudensky Alexander Y.
Published: November 2021

Regulatory T (Treg) cells represent a specialized lineage of suppressive CD4+ T cells, whose functionality is critically dependent on their ability to migrate to, and dwell in the proximity of cells they control. Here we show that continuous expression of the chemokine receptor CXCR4 in Treg cells is required for their ability to accumulate in the bone marrow (BM). Induced CXCR4 ablation in Treg cells led to their rapid depletion and consequent increase in mature B cells, foremost B-1 subset, observed exclusively in the BM without detectable changes in plasma cells or hematopoietic stem cells or any signs of systemic or local immune activation elsewhere. Dysregulation of BM B-1 B cells was associated with a highly specific increase in IgM autoantibodies and the total serum IgM levels. Thus, Treg cells control autoreactive B-1 B cells in a CXCR4-dependent manner. These findings have significant implications for understanding of regulation of B cell autoreactivity and malignancies.
Chromosome 1q amplification perturbs a ceRNA network to promote melanoma metastasis
Authors: Xu Xiaonan , Wang Kaizhen , Vera Olga , Verma Akanksha , Elemento Olivier , Yu Xiaoqing , Karreth Florian A.
Published: November 2021

Somatic copy number alterations (CNAs) promote cancer, but the underlying driver genes are often not obvious when only the functions of the encoded proteins are considered. mRNAs can act as competitive endogenous miRNA sponges (ceRNAs) to post-transcriptionally regulate gene expression in a protein coding-independent manner. However, whether ceRNAs contribute to the oncogenic effects of CNAs is unknown. We report that chromosome 1q gains promote melanoma progression and metastasis at least in part through overexpression of three mRNAs with ceRNA activity: CEP170, NUCKS1, and ZC3H11A. Genetic studies reveal that these ceRNAs enhance melanoma metastasis by sequestering tumor suppressor miRNAs, thereby alleviating the repression of several pro-metastatic target genes. This regulatory RNA network is evident in other cancer types, suggesting that chromosome 1q ceRNA deregulation is a common driver of cancer progression. Taken together, our work demonstrates that ceRNAs mediate the oncogenicity of somatic CNAs.
Rapid reconstruction of neural circuits using tissue expansion and lattice light sheet microscopy
Authors: Lillvis Joshua L. , Otsuna Hideo , Ding Xiaoyu , Pisarev Igor , Kawase Takashi , Colonell Jennifer , Rokicki Konrad , Goina Cristian , Gao Ruixuan , Hu Amy , Wang Kaiyu , Bogovic John , Milkie Daniel E. , Meienberg Linus , Boyden Edward S. , Saalfeld Stephan , Tillberg Paul W. , Dickson Barry J.
Published: November 2021

Electron microscopy (EM) allows for the reconstruction of dense neuronal connectomes but suffers from low throughput, limiting its application to small numbers of reference specimens. We developed a protocol and analysis pipeline using tissue expansion and lattice light-sheet microscopy (ExLLSM) to rapidly reconstruct selected circuits across many samples with single synapse resolution and molecular contrast. We validate this approach in Drosophila, demonstrating that it yields synaptic counts similar to those obtained by EM, can be used to compare counts across sex and experience, and to correlate structural connectivity with functional connectivity. This approach fills a critical methodological gap in studying variability in the structure and function of neural circuits across individuals within and between species.
Multiplexed Cell-Based Diagnostic Devices for Detection of Renal Biomarkers Using Genetic Circuits
Authors: Köse Sıla , Ahan Recep Erdem , Köksaldı İlkay Çisil , Olgaç Muazzez Asburçe Bike , Kasapkara Çiğdem Seher , Şeker Urartu Özgür Şafak
Published: November 2021

The number of synthetic biology based solutions employed in the medical industry is growing every year. The whole cell biosensors being one of them, have been proven valuable tools for developing low-cost, portable, personalized medicine alternatives to conventional techniques. Based on this concept, we targeted one of the major health problems in the world, Chronic Kidney Disease (CKD). To do so, we developed two novel biosensors for the detection of two important renal biomarkers; urea and uric acid. Using advanced gene expression control strategies we improved the operational range and the response profiles of each biosensor to meet clinical specifications. We further engineered these systems to enable multiplexed detection as well as an AND-logic gate operating system. Finally, we tested the applicability of these systems and optimized their working dynamics inside complex medium human blood serum. This study could help the efforts to transition from labor-intensive and expensive laboratory techniques to widely available, portable, low cost diagnostic options.
Elevated Plasma Matrix Metalloproteinase-8 associates with Sputum Culture Positivity in Pulmonary Tuberculosis
Authors: Walker N.F. , Karim F. , Moosa M.Y.S. , Moodley S. , Mazibuko M. , Khan K. , Sterling T.R. , van der Heijden Y.F. , Grant A.D. , Elkington P.T. , Pym A. , Leslie A.
Published: November 2021

Current methods for tuberculosis (TB) treatment monitoring are suboptimal. We evaluated plasma matrix metalloproteinase (MMP) and procollagen III N-terminal propeptide concentrations before and during TB treatment as biomarkers. Plasma MMP-1, -8 and -10 significantly decreased during treatment. Plasma MMP-8 was increased in sputum Mycobacterium tuberculosis culture positive relative to culture negative participants, prior to (median 4609 pg/ml, IQR 2353-9048 vs 775 pg/ml, IQR 551-4920, p=0.019) and after 6 months (median 3650, IQR 1214-3888 vs 720, IQR 551-1321, p=0.008) of TB treatment. Consequently, plasma MMP-8 is a potential biomarker to enhance TB treatment monitoring and screen for possible culture positivity.
Comparative analysis of antibody production by mRNA 1273, AZD 1222 and BBIBP-CorV on elderly people suffering from different co-morbidity in Bangladesh
Authors: Hoque Ashraful , Rahman Md Marufur , Parvez Shahnewaz , Imam Hossain , Nahar Nurun , Hasan Chowdhury Forhad Uddin
Published: November 2021

Background

As the pandemic spread so quickly all over the world, the scientist did not get the right time to cover all age group populations for a vaccine trial. The elderly population is usually vulnerable for COVID-19 which was proven by different research work and focus was to save this group of people was the prime concern for every country of the world. Though vaccines that got emergency use authorization have proven their efficacy which one is better for elderly people suffering from different co-morbid conditions is still not established. In this study, we want to evaluate the antibody production by mRNA 1273, AZD 1222, and BBIBP-CorV in elderly people with different comorbidity.

Method

We include 40 people in each group who have at least one comorbid condition and the total sample size was 120. The sample was taken from them before vaccination and 14 days after the second dose. Adverse event following immunization was recorded if any. Antibody measurement was done by ELISA method by using DiaSino SARS-CoV-2 S1 RBD IgG Quant.

Result

Among 120 participants with an equal number of participants in each of the vaccine groups all of them were aged between 60-72 years, of whom 65% were males and 35 % were females. Anti S1 RBD IgG was detected among all the participants from each vaccine group after 14 days of taking their 2nd dose. A non-parametric multiple comparison test (Kruskal-Wallis test) of Anti S1 RBD IgG levels among three vaccine groups revealed significant differences (P-value <0.05) between groups. The IgG level was almost twice in the mRNA-1273 group (mean 577.1± 44.33 AU/ml) compared to AZD1222(mean 308.5 ±37.91 AU/ml) and BBIBP-CorV group.

Conclusion

From this small sample size, we predicate that mRNA 1273 produce much higher anti-S1 RBD IgG than the other two vaccines. Every vaccine is safe and effective whose is approved by WHO. Calculative use of the vaccine may produce an outcome for the future as we are still way behind in the proper amount of vaccine production.