bluuebunny/crossref_metadata_2025 huggingface dataset:
SoUthern Cluster sCale Extended Source Survey (SUCCESS): a GMRT and Meerkat study of nine massive galaxy clusters
Authors: Kale R , Parekh V , Rahaman M , Joshi D C , Venturi T , Kolokythas K , Chibueze J O , Sikhosana S , Pillay D , Knowles K
Published: June 2022

We aim to carry out a radio study of the SoUthern Cluster sCale Extended Source Survey (SUCCESS) sample consisting of 20 massive (M500 > 5 × 1014 M⊙), nearby (redshift <0.3) and southern (−50° < δ < −30°) galaxy clusters detected by the Planck satellite and the South Pole Telescope. Here, we report targeted GMRT observations (325/610 MHz) for a subsample of nine clusters. We also use the first data release of MeerKAT Galaxy Cluster Legacy Survey (1283 MHz) for five of these nine clusters. The properties of the mini-halo in RXC J0528.9-3927, a candidate mini-halo in A3322, the radio halo and candidate double relics in A3399, and the radio halo in RXC J0232.2-4420 are presented. We also report a detection of candidate radio relics at distances 1 and 1.9 Mpc from the centre of RXC J0232.2-4420. The southeast relic of A3399 is consistent with the radio power–mass scaling relation for radio relics, while the candidate relics around RXC J0232.2-4420 are outliers. This indicates an origin of the candidate relics near RXC J0232.2-4420 to be independent of this cluster and a cluster merger-shock origin for the relic in A3399. In this subsample of clusters, 1/9 hosts a radio halo and double relics, 1/9 hosts a radio halo and 2/9 host mini-haloes. The dynamical states based on X-ray morphology show that A3399 is a disturbed cluster; however, the radio halo cluster RXC J0232.2-4420 is relaxed, and the mini-halo clusters have intermediate morphologies, adding to the cases of the less commonly found associations.
TOI-2119: a transiting brown dwarf orbiting an active M-dwarf from NASA’s TESS mission
Authors: Carmichael Theron W , Irwin Jonathan M , Murgas Felipe , Pallé Enric , Stassun Keivan G , Bartnik Matthew , Collins Karen A , de Leon Jerome , Esparza-Borges Emma , Fedewa Jeremy , Fong William , Fukui Akihiko , Jenkins Jon M , Kagetani Taiki , Latham David W , Lund Michael B , Mann Andrew W , Moldovan Dan , Morgan Edward H , Narita Norio , Painter Shane , Parviainen Hannu , Quintana Elisa V , Ricker George R , Schulte Jack , Schwarz Richard P , Seager Sara , Sokolovsky Kirill , Twicken Joseph D , Winn Joshua N
Published: June 2022

We report the discovery of TOI-2119b, a transiting brown dwarf (BD) that orbits and is completely eclipsed by an active M-dwarf star. Using light-curve data from the Transiting Exoplanet Survey Satellite mission and follow-up high-resolution Doppler spectroscopic observations, we find the BD has a radius of Rb = 1.08 ± 0.03RJ, a mass of Mb = 64.4 ± 2.3MJ, an orbital period of P = 7.200865 ± 0.00002 d, and an eccentricity of e = 0.337 ± 0.002. The host star has a mass of M⋆ = 0.53 ± 0.02M⊙, a radius of R⋆ = 0.50 ± 0.01R⊙, an effective temperature of Teff = 3621 ± 48K, and a metallicity of $\rm [Fe/H]=+0.06\pm 0.08$. TOI-2119b joins an emerging population of transiting BDs around M-dwarf host stars, with TOI-2119 being the ninth such system. These M-dwarf–brown dwarf systems typically occupy mass ratios near q = Mb/M⋆ ≈ 0.1−0.2, which separates them from the typical mass ratios for systems with transiting substellar objects and giant exoplanets that orbit more massive stars. The nature of the secondary eclipse of the BD by the star enables us to estimate the effective temperature of the substellar object to be 2030 ± 84K, which is consistent with predictions by substellar evolutionary models.
China's goal of achieving carbon neutrality before 2060: experts explain how
Authors: Zhao Weijie
Published: June 2022

‘We aim to have CO2 emissions peak before 2030 and achieve carbon neutrality before 2060,’ President Xi Jinping so declared at the General Debate of the 75th United Nations General Assembly on 22 September 2020. More than 130 countries globally have proposed their own carbon neutrality goals by 2050 or 2060. Thus, carbon neutrality is a collective effort of human societies to cope with the climate crisis. If all countries could follow their own plans and reach carbon neutrality in a few decades, we may have a chance to control global warming within 1.5 or 2oC, confining climate change to a relatively safe zone. As a developing country with a large population, high coal consumption and large manufacturing industries, can China achieve the huge task of societal transformation that will enable carbon peaking and carbon neutrality within the next four decades? How will China transform traditional power generation and manufacturing industries, as well as create new technologies for carbon capture and storage? In this panel discussion chaired by Prof. Xinhe Bao, a scientist of energy and chemistry, top experts gathered to discuss the challenges and potential solutions, outlining the coming ‘green industrial revolution’.

Huiming Cheng

Professor, Institute of Metal Research, Chinese Academy of Sciences; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences

Zhengtang Guo

Professor, Institute of Geology and Geophysics, Chinese Academy of Sciences

Yaling He

Professor, School of Energy and Power Engineering, Xi’an Jiaotong University

Zheng Li

Professor, Institute of Climate Change and Sustainable Development, Tsinghua University

Minggao Ouyang

Professor, School of Vehicle and Mobility, Tsinghua University

Zhengrong Shi

Professor, College of Energy and Mechanical Engineering, Shanghai University of Electric Power

Zaiku Xie

Professor, China Petroleum and Chemical Corporation (SINOPEC)

Xinhe Bao (Chair)

Professor, University of Science and Technology of China, and Dalian Institute of Chemical Physics, Chinese Academy of Sciences
Tool-use Extends Peripersonal Space Boundaries in Schizophrenic Patients
Authors: Ferroni Francesca , Ardizzi Martina , Magnani Francesca , Ferri Francesca , Langiulli Nunzio , Rastelli Francesca , Lucarini Valeria , Giustozzi Francesca , Volpe Roberto , Marchesi Carlo , Tonna Matteo , Gallese Vittorio
Published: June 2022

Background and Hypothesis

A primary disruption of the bodily self is considered a core feature of schizophrenia (SCZ). The “disembodied” self might be underpinned by inefficient body-related multisensory integration processes, normally occurring in the peripersonal space (PPS), a plastic sector of space surrounding the body whose extent is altered in SCZ. Although PPS is a malleable interface marking the perceptual border between self and others, no study has addressed the potential alteration of its plasticity in SCZ. We investigated the plasticity of PPS in SCZ patients after a motor training with a tool in the far space.

Study Design

Twenty-seven SCZ patients and 32 healthy controls (HC) underwent an audio-tactile task to estimate PPS boundary before (Session 1) and after (Session 3) the tool-use. Parameters of PPS, including the size and the slope of the psychometric function describing audio-tactile RTs as a function of the audio-tactile distances, were estimated.

Study Results

Results confirm a narrow PPS extent in SCZ. Surprisingly, we found PPS expansion in both groups, thus showing for the first time a preserved PPS plasticity in SCZ. Patients experienced a weaker differentiation from others, as indicated by a shallower PPS slope at Session 1 that correlated positively with negative symptoms. However, at Session 3, patients marked their bodily boundary in a steeper way, suggesting a sharper demarcation of PPS boundaries after the action with the tool.

Conclusions

These findings highlight the importance of investigating the multisensory and motor roots of self-disorders, paving the way for future body-centred rehabilitation interventions that could improve patients’ altered body boundary.
“This Patriarchal, Machista and Unequal Culture of Ours”: Obstacles to Confronting Conflict-Related Sexual Violence
Authors: Kreft Anne-Kathrin
Published: June 2022

Prior research has established that conflict-related sexual violence against women is anchored in patriarchal norms and practices that assert gendered hierarchies. What remains relatively underresearched, however, is how patriarchal structures shape individual, social, and institutional responses to conflict-related sexual violence and its victims. This article sets out to shed light on this question, identifying different social and institutional processes that impede efforts to confront conflict-related sexual violence. The analysis of interviews with Colombian civil society activists illustrates how patriarchal norms and practices normalize sexual violence in society, but also ostracize, stigmatize, and ultimately seek to silence its victims. This risks obliterating conflict-related sexual violence from the political map and severely undermines the pursuit of justice. Power imbalances disadvantaging and further marginalizing the victims permeate these processes. Civil society organizations play an important role in reclaiming power for the victims, by overcoming disabling silences, making sexual violence visible, and confronting harmful patriarchal practices.
Penile Chylorrhea as a Rare Presentation of Penile Lymphangioma Circumscriptum Reconstructed with Deep External Pudendal Artery Perforator Flap
Authors: Abd Al-Moktader Magdy A. , Ayad Wael , Zayid Tarek , Ouf Mohamed Osama , Youssif Sherif Hamdeno , Dahshan Hazem , Shoulkami Khalad , Khalifa Mohamed Hosny
Published: June 2022

Chylorrhea, a chylous (white viscid) discharge from the external urethral penile opening, is unrelated to urination and is a rare presentation of lymphangioma circumscriptum in the penis that can significantly impair a patient’s quality of life and psychological well-being. Herein, we present a case of recurrent chylorrhea that was detected using diagnostic tools and treated using the deep external pudendal artery perforator flap in the inner thigh, which is extremely rich in lymphatic vessels and lymph nodes.
Should Acupuncture-Related Therapies be Considered in Prediabetes Control? Results From a Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Zhang Min , Wang Carol Chunfeng , Lo Johnny
Published: June 2022

To assess the effects and safety of acupuncture-related therapy (AT) interventions on glycemic control for prediabetes, we systematically searched 14 databases and 5 clinical registry platforms from inception to December 2020. Randomized controlled trials involving AT interventions for managing prediabetes were included (PROSPERO registration no. CRD42020209809). Of the 855 identified trials, 34 articles were included for qualitative synthesis, 31 of which were included in the final meta-analysis. Compared with usual care, sham intervention, or conventional medicine, AT treatments yielded greater reductions in the primary outcomes, including fasting plasma glucose (FPG) (standard mean difference [SMD] = −0.83; 95% confidence interval [CI], −1.06, −0.61; P < .00001), 2-hour plasma glucose (2hPG) (SMD = −0.88; 95% CI, −1.20, −0.57; P < .00001), and glycated hemoglobin (HbA1c) levels (SMD = −0.91; 95% CI, −1.31, −0.51; P < .00001), as well as a greater decline in the secondary outcome, which is the incidence of prediabetes (RR = 1.43; 95% CI, 1.26, 1.63; P < .00001). AT is thus a potential strategy that can contribute to better glycemic control in the management of prediabetes. Because of the substantial clinical heterogeneity, the effect estimates should be interpreted with caution. More research is required for different ethnic groups and long-term effectiveness.
The Effect of Progressive Muscle Relaxation and Deep Breathing Exercises on Dyspnea and Fatigue Symptoms of COPD Patients
Authors: Neşe Adile , Samancıoğlu Bağlama Sevgin
Published: June 2022

This study was conducted to examine the effect of progressive muscle relaxation and deep breathing exercises applied to patients diagnosed with chronic obstructive pulmonary disease (COPD) on their dyspnea and fatigue symptoms. The study was a randomized controlled experimental trial and comprised 116 COPD patients who applied to a chest diseases follow-up outpatient clinic hospital located in Gaziantep, Turkey. The data were collected using the “Patient Information Form” including sociodemographic and disease-related characteristics of the patients, COPD and Asthma Fatigue Scale (CAFS), and Dyspnea-12 Scale. Dyspnea-12 Scale and CAFS total scores of the patients in the intervention group showed a statistically significant difference before and after the Progressive Relaxation Exercise and Deep Breathing Exercise applications (P < .05). Although the Dyspnea-12 Scale and CAFS total mean scores showed an increase in the intervention group, they remained the same in the control group. In the present study, it was found that the Progressive Muscle Relaxation Exercise and Deep Breathing Exercise applied to COPD patients were effective in decreasing their dyspnea and fatigue symptoms.
Characterization of Eosinophilic Esophagitis From the European Pediatric Eosinophilic Esophagitis Registry (pEEr) of ESPGHAN
Authors: Oliva Salvatore , Dias Jorge Amil , Rea Francesca , Malamisura Monica , Espinheira Maria Céu , Papadopoulou Alexandra , Koutri Eleni , Rossetti Danilo , Orel Rok , Homan Matjaž , Bauraind Olivia , Auth Marcus Karl-Heinz , Junquera Carolina Gutierrez , Vande Velde Saskia , Kori Michal , Huysentruyt Koen , Urbonas Vaidotas , Roma Eleftheria , Fernández Sonia Fernández , Domínguez-Ortega Gloria , Zifman Eyal , Kafritsa Panayota , Miele Erasmo , Zevit Noam ,   on behalf of the ESPGHAN EGID Working Group
Published: June 2022

Objectives:

Few pediatric data on phenotypic aspects of eosinophilic esophagitis (EoE) are available. The pEEr registry was developed to prospectively characterize children with EoE from Europe and Israel.

Methods:

pEEr is an ongoing prospective registry enrolling children with esophageal eosinophilia (≥15 eos/HPF). Anonymized data were collected from 19 pediatric centers. Data regarding demographics, clinical manifestations, endoscopy, histology, and therapies were collected.

Results:

A total of 582 subjects (61% male) were analyzed. The median age at diagnosis was 10.5 years [interquartile range (IQR): 5.7–17.7], whereas the age at symptom onset was 9.2 years (IQR: 4.3–16.4), resulting in a median diagnostic delay of 1.2 years (IQR: 0.7–2.3). The diagnostic delay was longer below age <6 years. Shorter diagnostic delays were associated with the presence of food allergy or a family history for EoE. Symptoms varied by age with dysphagia and food impaction more common in adolescents, while vomiting and failure to thrive more common in younger children (P < 0.001). Among endoscopic findings, esophageal rings were more common in adolescents, whereas exudates were more frequent in younger children(P < 0.001). Patients who responded to proton pump inhibitors (PPIs) were more likely to be older, males, and less often presented severe endoscopic findings. Patients unresponsive to PPIs received topical steroids (40%), elimination diet (41%), or a combined therapy (19%).

Conclusions:

EoE findings vary according to age in pediatric EoE. Young children are commonly characterized by non-specific symptoms, atopic dermatitis, food allergy, and inflammatory endoscopic lesions. Adolescents usually have dysphagia or food impaction, fibrostenotic lesions, and a better PPI response.
A Conversation Between Past and Present Chairs of the American Board of Physical Medicine and Rehabilitation
Authors: Ditunno John F. , Cohen B. Stanley , Melvin John L. , DeLisa Joel A. , Walsh Nicolas E. , Turk Margaret A. , Matthews Dennis J. , Massagli Teresa L. , Kowalske Karen J. , Chiodo Anthony E. , McDeavitt James T.
Published: June 2022

On the 75th anniversary of the founding of the American Board of Physical Medicine and Rehabilitation, 11 of the surviving chairs of the board convened virtually to reflect on the past 40 years of major trends for the accrediting body of physiatrists. The field rapidly expanded in the 1980s, driven by changes in the reimbursement environment. This rapid expansion drove an improvement in the caliber of residents choosing the field and in the quality of training programs. As physical medicine and rehabilitation evolved from a small- to medium-sized specialty, the board addressed many challenges: securing a credible position within the American Board of Medical Specialties; addressing a rising demand for subspecialty certification; improving training and exposure to physiatry; enhancing the quality of the accreditation process; and reducing the burden of accreditation on diplomates. The future development of physiatry includes improving diversity, equity, and inclusion, while restoring provider morale, well-being, and meaningfulness in work. Although challenges remain, physiatry as a field has grown to be well established through the board’s efforts and respected within the larger medical community.
Clinical Outcomes and Effectiveness of Heart Transplantation in Patients With Systemic Light-chain Cardiac Amyloidosis
Authors: Jeong Hyehyun , Hwang Inhwan , Kim Jwa Hoon , Cho Hyungwoo , Kim Min-Seok , Lee Sang Eun , Choi Hyo-In , Jung Sung-Ho , Lee Jae Won , Yun Tae-Jin , Park Jeong-Jun , Kim Miyoung , Go Heounjeong , Park Chan Sik , Yoon Dok Hyun , Kim Jae-Joong
Published: June 2022

Background.

In systemic light-chain (AL) amyloidosis, cardiac involvement is a major determinant of survival; however, cardiac response is limited even after systemic treatment in a majority of patients, and some require heart transplantation. Additionally, limited information is available on specific indications for heart transplantation. We aimed to explore clinical outcomes of cardiac amyloidosis and its association with heart transplantation, including identifying factors favoring heart transplantation amenability.

Methods.

We retrospectively analyzed data from patients diagnosed with AL amyloidosis with cardiac involvement between January 2007 and December 2020 at a tertiary referral center.

Results.

Among 73 patients, 72 (99%) received systemic treatment, and 12 (16%) underwent heart transplantation. Characteristics at diagnosis were similar between heart transplant recipients and nonrecipients, although left ventricular ejection fraction tended to be lower in recipients (median 48% versus 57%, P = 0.085). Eight weeks after systemic treatment, 67% and 12% of patients achieved hematologic and brain natriuretic peptide responses. Overall survival was longer among heart transplantation recipients than nonrecipients, with 5-y survival rates of 61.1% (95% confidence interval, 25.5%-83.8%) versus 32.0% (95% confidence interval, 20.3%-44.4%; P = 0.022), respectively. Among the 34 with identifiable causes of death out of 51 deaths, 21 nonrecipients (62%) died of cardiac problems compared with none in the heart transplant recipients. Additionally, survival outcomes favored heart transplant recipients in most subgroups, including patients with higher Mayo 2004 European stage at diagnosis and with extracardiac involvement of amyloidosis.

Conclusions.

Heart transplantation can achieve long-term survival in appropriately selected patients with AL cardiac amyloidosis.
Magnusiomyces siamensis sp. nov., a yeast-like fungus isolated from food waste
Authors: Dudhat Jemisha , Sakpuntoon Varunya , Angchuan Jirameth , Kaewwichian Rungluk , Srisuk Nantana
Published: June 2022

Three yeast strains, DMKU-GTSP8-6, DMKU-GTSP8-14T and DMKU-JED8-73, were isolated from food waste in Thailand. Based on the phenotypic characteristics and sequence analysis of the D1/D2 domain of the large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) region, it was revealed that the three strains clustered with the Magnusiomyces/Saprochaete clade. These strains were distinguished from the closely related species Saprochaete quercus CBS 750.85, Magnusiomyces ovetensis CBS 192.55T, Magnusiomyces starmeri CBS 780.96T, Saprochaete chiloensis CBS 8187T and Magnusiomyces ingens CBS 517.90T by 11.4, 13.1, 11.9, 11.2 and 12.6 % sequence divergence in the D1/D2 domain and by 34.6, 34.5, 33.6, 33.2 and 34.9 % sequence divergence in the ITS region, respectively. The new species, which does not produce ascospores, is described as Magnusiomyces siamensis. The holotype of Magnusiomyces siamensis is TBRC 15056T, and the isotypes are DMKU-GTSP8-14T and PYCC 9023T.
A systematic review and meta-analysis on effectiveness and safety of traditional Chinese medicine combined with EGFR-TKIs in treating advanced non-small cell lung cancer
Authors: Su Shanyang , Huang Yanling , Li Wenjia , Lu Xiang , Chen Xiaowan , Zhou Jihong
Published: June 2022

Introduction

EGFR-TKIs have been shown in multiple clinical trials to be effective in first-line therapy, but acquired resistance is inevitable regardless of the recent effect. EGFR-TKIs combined with TCM comprehensive therapy have shown unique effects in clinical randomized trials to increase the efficacy of radiotherapy and chemotherapy and gene-targeted drugs, reduce their adverse reactions, reduce the chance of recurrence and metastasis, enhance the immune recognition and killing of lung cancer cells, and reverse the multi-drug resistance of lung cancer cells. Therefore, our study aims to clarify the clinical efficacy, safety and benefit of EGFR-TKIs combined with TCM in the treatment of advanced non-small cell lung cancer.

Methods and Analysis

We will search four international electronic databases (PubMed, Cochrane Library, EMBASE and Web of Science) and four Chinese electronic databases (CNKI, VIP, WanFang, China Biology Medicine) to retrieve relevant literature. We only included studies from launch until publication in May 2022. The primary outcomes will include the Response Evaluation Criteria in Solid Tumours、 progression-free survival and effectiveness rate。 Secondary outcomes will include Karnofsky functional status scale, 1-year survival rate, and grading scale for common toxicities of anticancer drugs(WHO). Two reviewers will conduct independent research selection, data extraction, data synthesis and quality assessment. The assessment of bias risk and data synthesis will be conducted using Review Manager 5.3 software. Improved Jadad scale will be used to evaluate the quality of evidence.

Ethics and Dissemination

Because this systematic review will be conducted based on published research, there is no ethical approval requirement. The findings of this systematic review will be published in a peerreviewed journal.
In silico, in vitro, and in vivo models reveal EPHA2 as a target for decreasing inflammation and pathological endochondral ossification in osteoarthritis
Authors: Ferrao Blanco Mauricio N. , Lesage Raphaelle , Kops Nicole , Fahy Niamh , Bekedam Fjodor T. , Chavli Athina , Bastiaansen-Jenniskens Yvonne M. , Geris Liesbet , Chambers Mark G. , Pitsillides Andrew A. , Narcisi Roberto , van Osch Gerjo J.V.M.
Published: June 2022

Low-grade inflammation and pathological endochondral ossification are processes underlying the progression of osteoarthritis, the most prevalent joint disease worldwide. In this study, data mining on publicly available transcriptomic datasets revealed EPHA2, a receptor tyrosine kinase associated with cancer, to be associated with both inflammation and endochondral ossification in osteoarthritis. A computational model of cellular signaling networks in chondrocytes predicted that in silico activation of EPHA2 in healthy chondrocytes increases inflammatory mediators and triggers hypertrophic differentiation, the phenotypic switch characteristic of endochondral ossification. We then evaluated the effect of inhibition of EPHA2 in cultured human chondrocytes isolated from individuals with osteoarthritis and demonstrated that inhibition of EPHA2 indeed reduced inflammation and hypertrophy. Additionally, systemic subcutaneous administration of the EPHA2 inhibitor ALW-II-41-27 attenuated joint degeneration in a mouse osteoarthritic model, reducing local inflammation and pathological endochondral ossification. Collectively, we demonstrate that pharmacological inhibition of EPHA2 with ALW-II-41-27 is a promising disease-modifying treatment that paves the way for a novel drug discovery pipeline for osteoarthritis.
Closed-loop control and recalibration of place cells by optic flow
Authors: Madhav Manu S. , Jayakumar Ravikrishnan P. , Li Brian , Savelli Francesco , Knierim James J. , Cowan Noah J.
Published: June 2022

Understanding the interplay between sensory input, endogenous neural dynamics, and behavioral output is key toward understanding the principles of neural computation. Hippocampal place cells are an ideal system to investigate this closed-loop interaction, as they are influenced by both self-motion (idiothetic) signals and by external sensory landmarks as an animal navigates its environment1–9. To continuously update a position signal on an internal “cognitive map”, the hippocampal system integrates self-motion signals over time10,11. In the absence of stable, external landmarks, however, these spatial correlates of neuronal activity can quickly accumulate error and cause the internal representation of position or direction to drift relative to the external environment1,5. We have previously demonstrated that, in addition to their known roles in preventing and/or correcting path-integration error, external landmarks can be used as a putative teaching signal to recalibrate the gain of the path integration system6. However, it remains unclear whether idiothetic cues, such as optic flow, exert sufficient influence on the cognitive map to enable recalibration of path integration, or if instead an unambiguous allocentric frame of reference, anchored by polarizing landmark information, is essential for path integration recalibration. Here, we use principles of control theory12,13 to demonstrate systematic control of place fields by pure optic flow information in freely moving animals by using a neurally closed-loop virtual reality system that adjusts optic flow speed as a function of real-time decoding of the hippocampal spatial map. Using this “cognitive clamp”, we show that we can not only bring the updating of the map under control of the optic flow cues but we can also elicit recalibration of path integration. This finding demonstrates that the brain continuously rebalances the influence of conflicting idiothetic cues to fine-tune the neural dynamics of path integration, and that this recalibration process does not require a top-down, unambiguous position signal from landmarks.
Real-time imaging of mitochondrial redox reveals increased mitochondrial oxidative stress associated with amyloid β aggregatesin vivoin a mouse model of Alzheimer’s disease
Authors: Calvo-Rodriguez Maria , Kharitonova Elizabeth K. , Snyder Austin C. , Hou Steven S. , Sanchez-Mico Maria Virtudes , Das Sudeshna , Fan Zhanyun , Shirani Hamid , Nilsson K. Peter R. , Serrano-Pozo Alberto , Bacskai Brian J.
Published: June 2022

Background

Reactive oxidative stress is a critical player in the amyloid beta (Aβ) toxicity that contributes to neurodegeneration in Alzheimer’s disease (AD). Mitochondrial damage, observed in AD, is one of the main sources of reactive oxygen species. Although Aβ causes neuronal mitochondria-associated reactive oxidative stressin vitro, this has never been directly observed in thein vivoliving brain. Here, we tested whether Aβ plaques and soluble oligomers induce mitochondrial oxidative stress in surrounding neuronsin vivo, and whether the neurotoxic effect can be abrogated using mitochondrial-targeted antioxidants.

Methods

We expressed a genetically encoded fluorescent ratiometric mitochondria-targeted reporter of oxidative stress in mouse models of the disease, and performed intravital multiphoton microscopy of neuronal mitochondria and Aβ plaques.

Results

For the first time, we demonstrated by direct observation exacerbated mitochondrial oxidative stress in neurons after both Aβ plaque deposition and direct application of soluble oligomeric Aβ onto the brain, and determined the most likely pathological sequence of events leading to oxidative stressin vivo. Oxidative stress could be inhibited by both blocking calcium influx into mitochondria and treating with the mitochondria-targeted antioxidant SS31.

Conclusions

Considering these results, mitochondria-targeted compounds hold promise as neuroprotective drugs for the prevention and/or treatment of AD.
Assessment of SLC25A46 variants in Parkinson’s disease
Authors: Liu Hui , Dehestani Mohammad , Makarious Mary B. , Bandres-Ciga Sara , Gasser Thomas , Kim Jonggeol J.
Published: June 2022

The SLC25A46 gene was recently reported to be associated with Parkinson’s disease (PD). Here, we comprehensively investigated the role of SLC25A46 variants in PD patients of European ancestry and assessed susceptibility using whole-genome sequencing data from 1647 patients with PD and 1050 healthy controls. Burden analysis of rare non-synonymous variants across case-control individuals from whole-genome data did not find evidence of SLC25A46 association with PD. Therefore, our results do not support a major role for SLC25A46 in PD in the European population and large-scale sequencing studies of family trios are necessary to further evaluate the role of SLC25A46 in PD etiology.
Management and outcomes of myelomeningocele-associated hydrocephalus in low- and middle-income countries: a systematic review and meta-analysis protocol
Authors: Takoutsing Berjo Dongmo , Touzet Alvaro Yanez , Park Jay J. , Lee Seong Hoon , Bligh Emily R. , Egiz Abdullah , Gillespie Conor S. , Figaji Anthony
Published: June 2022

Introduction

Hydrocephalus and myelomeningocele (MMC) place disproportionate burdens of disease on low and middle-income countries (LMICs). MMC-associated hydrocephalus and its sequelae result in a spectrum of severely devastating clinical manifestations, for which LMICs are disproportionately unprepared in terms of human, capital, and technological resources. This study aims to review and compare the management and outcomes of infant MMC-associated hydrocephalus in LMICs and high-income countries.

Methods and analysis

This systematic review and meta-analysis will follow the PRISMA 2020 guidelines. The following databases will be searched without restrictions on language, publication date, or country of origin: EMBASE, MEDLINE, The Cochrane Library, Global Index Medicus, African Journals Online, and SciELO. All peer-reviewed studies of primary data reporting management and outcomes of infant MMC-associated hydrocephalus will be included. Where high-quality homogeneous studies exist, meta-analyses will be conducted to compare the management and outcomes of MMC-associated hydrocephalus across socioeconomic and geographic regions of the world. The primary outcome will be treatment failure of the first-line hydrocephalus treatment, which we defined operationally as the performance of a second intervention for the same reason as the first. Secondary outcomes include time to failure, rates of mortality, and postoperative complications.

Ethics and dissemination

Ethical approval was not applicable because this study does not involve human participants. Dissemination strategies will include publication in a peer-reviewed journal, oral and poster presentations at conferences, and an interactive web application to facilitate interaction with the findings and promote the discussion and sharing of findings on social media.

ARTICLE SUMMARY

Strengths and limitations of this study

This review focuses on multiple treatment modes of a well-defined disease population.

Six electronic databases that are commonly used across both high- and low-income countries will be searched.

No restrictions on language, location, or publication date were placed during screening.

Unpublished studies will not be sought.

The representativeness of the sample will rely on the quality of reporting of myelomeningocoele-associated hydrocephalus in the literature.

Only one operational definition of treatment failure—‘the performance of a second intervention for the same reason as the first’—will be sought.

An interactive web application dashboard will be developed to facilitate the transparent interaction with our methods and findings and promote scientific discussion and scrutiny.
A causal role of the human left temporoparietal junction in computing social influence during goal-directed learning
Authors: Zhang Lei , Kandil Farid I. , Zhao Ke , Fu Xiaolan , Lamm Claus , Hilgetag Claus C. , Gläscher Jan
Published: June 2022

The human temporoparietal junction (TPJ) is a brain area crucial for processing social information. Although brain stimulation studies have started to explore the causal function of TPJ under social contexts, few have explicitly considered bilateral TPJ as target regions. Here, leveraging non-invasive continuous theta-burst stimulation (cTBS) and hierarchical Bayesian computational modeling, we tested whether left or right TPJ (with vertex as control) is causally involved in how dissenting choices by others influence individuals’ choice adjustments in goal-directed learning. In our social learning paradigm, participants (N = 31) first made their private decision, and then were allowed to re-adjust their choices after observing choices of four other players. Behaviorally, we show that disruption of the left, but not the right TPJ, weakened participants’ choice adjustment and delayed their response speed when confronted with dissenting information from the other players. Computationally, disrupting activity in the left TPJ attenuated the degree of computing social influence during choice adjustment, whereas the extent to which how observational learning from others’ choices was integrated into direct learning remained intact. Together, our results provide evidence for the causal role of left TPJ in social influence during goal-directed learning and shed light on the relational function (with respect to oneself) of the TPJ in social cognition.
Comparative immune responses toMycobacterium tuberculosisin people with latent infection or sterilizing protection
Authors: Jalbert Emilie , Liu Cuining , Mave Vidya , Lang Nancy , Kagal Anju , Valvi Chhaya , Paradkar Mandar , Gupte Nikhil , Lokhande Rahul , Bharadwaj Renu , Kulkarni Vandana , Gupta Amita , Weinberg Adriana
Published: June 2022

Tuberculosis (TB) affects 2 billion people worldwide and causes 1.5 million deaths every year. There is great need for new TB vaccines that are more efficacious than the currently licensed BCG vaccine, which provides only limited protection. Our goal was to identify potential targets for new TB vaccines by characterizing the immune responses that distinguish individuals with sterilizing protection against TB (TB-resisters), defined by presence of TB-specific immune responses and absence of latent infection, from individuals with latent TB infection (LTBI-participants).

Cryopreserved peripheral blood mononuclear cells (PBMC) from 13 TB-resisters and 10 LTBI-participants were analyzed by high dimensional spectral flow cytometry after overnightM. tuberculosis (Mtb)antigenic stimulation or unstimulated control. Activation of conventional and nonconventional T cells, NK cells, and antigen presenting cells (APC) was compared between the two groups. Compared with LTBI-participants, TB-resisters had significantly higher proportions of conventional and nonconventional T cells expressing granzyme B (GranzB) and PD-1, and of polyfunctional cells in unstimulated andMtb-stimulated conditions. Conversely LTBI-participants had higher expression of CD25, CD69, CD107a, IL10 and IFNγ. An unbiased cluster analysis revealed higher frequency of recently described CD8+GMM+GranzB+ T cells in unstimulated PBMC from TB-resisters than LTBI-participants. APC activation revealed very few differences between TB-resisters and LTBI-participants. An exploratory analysis of responses in 14 BCG-recipients with minimal exposure to TB showed multiple differences with TB-resisters and LTBI-participants in PBMC activation; lower polyfunctionality of T cells and APC inMtb-stimulated PBMC; and absence of CD8+GMM+GranzB+ T cells.

We conclude that combined increased T cell expression of GranzB and checkpoint inhibitors may contribute to immune protection against TB and may be targeted by new vaccines.
Structural insights into AT-rich DNA recognition by SALL family proteins
Authors: Ru Wenwen , Koga Tomoyuki , Wang Xiaoyang , Guo Qiong , Gearhart Micha , Zhao Shidong , Murphy Mark , Kawakami Hiroko , Corcoran Dylan , Zhang Jiahai , Zhu Zhongliang , Yao Xuebiao , Kawakami Yasu , Xu Chao
Published: June 2022

Spalt-like 4 (SALL4) plays an essential role in controlling the pluripotent property of embryonic stem cells (ESCs) via binding to AT-rich regions of genomic DNA. Here we present crystal structures of the the zinc finger cluster 4 (ZFC4) domain of SALL4 (SALL4ZFC4) bound with different double stranded DNAs containing a conserved AT-rich motif. In the structures, two zinc fingers of SALL4ZFC4 coordinatively recognize an AATA tetranucleotide. We also solved the DNA-bound structures of SALL3ZFC4 and SALL4ZFC1. These structures illuminate a common recognition mode for AT-rich DNA by the SALL family proteins. The DNA binding activity is essential for SALL4 function as DNA-binding defective mutants of mouse Sall4 failed to repress aberrant gene expression in Sall4-/- mESCs. Thus, these analyses provide new insights into the mechanisms of action underlying SALL family in controlling cell fate via preferentially targeted to AT-rich sites within genomic DNAs during cell differentiation.
Novel Genetic Loci Associated with Osteoarthritis in Multi-Ancestry Analyses in 484,374 Participants from MVP and the UK Biobank
Authors: McDonald Merry-Lynn N. , Kumar Preeti Lakshman , Srinivasasainagendra Vinodh , Nair Ashwathy , Rocco Alison , Wilson Ava C. , Chiles Joe , Richman Joshua , Pinson Sarah A. , Dennis Richard , Jagadale Vivek , Brown Cynthia , Pyarajan Saiju , Tiwari Hemant K. , Bamman Marcas M. , Singh Jasvinder A. ,   the VA Million Veteran Program
Published: June 2022

To date there have been no large multi ancestry genetic studies of osteoarthritis (OA). We leveraged the unique resources of 484,374 participants in the Million Veteran Program (MVP) and UK Biobank to address this gap. Analyses included participants of European, African, Asian and Hispanic descent. We discovered OA associated genetic variation in 10 loci and replicated association findings from previous OA studies. We also present evidence some OA-associated regions are robust to population ancestry. Drug repurposing analyses revealed enrichment of targets of several medication classes and provide potential insight to etiology of beneficial effects of antiepileptics on OA pain.
Machine learning aided multiscale modelling of the HIV-1 infection in the presence of NRTI therapy
Authors: Tunc Huseyin , Sari Murat , Kotil Seyfullah
Published: June 2022

The Human Immunodeficiency Virus (HIV) is one of the most common chronic infectious diseases of humans. Increasing the expected lifetime of the patients depends on the use of optimal antiretroviral therapies. The emergence of the drug-resistant strains may decrease the effects of treatments and lead to Acquired Immune Deficiency Syndrome (AIDS) even if the existence of antiretroviral therapy. Investigation of the genotype-phenotype relations is a crucial process to optimize the therapy protocols of the patients. Here we propose a mathematical modelling framework to address the effect of initial strains, initiation timing and adherence levels of nucleotide reverse transcriptase inhibitors (NRTI) on the emergence of a possible AIDS phase. For the first time, we have combined the existing Stanford HIV drug resistance data with a multi-strain within-host ordinary differential equation (ODE) model to track the dynamics of most common NRTI resistant strains. Regardless of the drug choice, the late initiation and poor adherence levels to the NRTI therapy increase the probability of the emergence of the AIDS phase. Overall, the 3TC, D4T-AZT and TDF-D4T drug combinations provide higher success rates. The results are in line with genotype-phenotype data and pharmacokinetic parameters of the NRTI inhibitors, but we show the heavy influence of neighbour viral strains of the initial ones has a considerable effect on the success/failure rates. Improving multiscale models can contribute to understanding the disease progression and treatment options.
Application of machine learning and complex network measures to an EEG dataset from DMT experiments
Authors: Alves Caroline L. , Toutain Thaise G. L. de O. , Porto Joel Augusto Moura , Pineda Aruane M. , de Sena Eduardo Pondé , Rodrigues Francisco A. , Thielemann Christiane , Ciba Manuel
Published: June 2022

There is a growing interest in the medical use of psychedelic substances as preliminary studies using them for psychiatric disorders have shown positive results. In particularly, one of these substances is N,N-dimethyltryptamine (DMT) an agonist serotonergic psychedelic that can induce profound alterations in state of consciousness.

In this work, we propose a computational method based on machine learning as an exploratory tool to reveal DMT-induced changes in brain activity using EEG data and provide new insights into the mechanisms of action of this psychedelic substance. To answer these questions, we propose a two-class classification based on (A) the connectivity matrix or (B) complex network measures derived from it as input to a support vector machine We found that both approaches were able to automatically detect changes in the brain activity, with case (B) showing the highest AUC (89%), indicating that complex network measurements best capture the brain changes that occur due to DMT use. In a second step, we ranked the features that contributed most to this result. For case (A) we found that differences in the high alpha, low beta, and delta frequency band were most important to distinguish between the state before and after DMT inhalation, which is consistent with results described in the literature. Further, the connection between the temporal (TP8) and central cortex (C3) and between the precentral gyrus (FC5) and the lateral occipital cortex (T8) contributed most to the classification result. The connection between regions TP8 and C3 has been found in the literature associated with finger movements that might have occurred during DMT consumption. However, the connection between cortical regions FC5 and P8 has not been found in the literature and is presumably related to emotional, visual, sensory, perceptual, and mystical experiences of the volunteers during DMT consumption. For case (B) closeness centrality was the most important complex network measure. Moreover, we found larger communities and a longer average path length with the use of DMT and the opposite in its absence indicating that the balance between functional segregation and integration was disrupted. This findings supports the idea that cortical brain activity becomes more entropic under psychedelics.

Overall, a robust computational workflow has been developed here with an interpretability of how DMT (or other psychedelics) modify brain networks and insights into their mechanism of action. Finally, the same methodology applied here may be useful in interpreting EEG time series from patients who consumed other psychedelic drugs and can help obtain a detailed understanding of functional changes in the neural network of the brain as a result of drug administration.
JASPER: a fast genome polishing tool that improves accuracy and creates population-specific reference genomes
Authors: Guo Alina , Salzberg Steven L. , Zimin Aleksey V.
Published: June 2022

Advances in long-read sequencing technologies have dramatically improved the contiguity and completeness of genome assemblies. Using the latest nanopore-based sequencers, we can generate enough data for the assembly of a human genome from a single flow cell. With the long-read data from these sequences, we can now routinely produce de novo genome assemblies in which half or more of a genome is contained in megabase-scale contigs. Assemblies produced from nanopore data alone, though, have relatively high error rates and can benefit from a process called polishing, in which more-accurate reads are used to correct errors in the consensus sequence. In this manuscript, we present a novel tool for genome polishing called JASPER (Jellyfish-based Assembly Sequence Polisher for Error Reduction). In contrast to other polishing methods, JASPER gains efficiency by avoiding the alignment of reads to the assembly. Instead, JASPER uses a database of k-mer counts that it creates from the reads to detect and correct errors in the consensus. In addition to its use for polishing genomes, JASPER can also create population-specific genomes using an existing reference genome along with sequencing reads from multiple individuals from the population of interest. In this mode, JASPER alters the reference genome so that it contains variants that are common in the target population. In our experiments, we show that after creating a Japanese-specific reference genome, we observed a 27% reduction in homozygous variant calls using whole-genome sequencing reads from an individual from Tokyo.
PICLN modulates alternative splicing and ensures adaptation to light and temperature changes in plants
Authors: Mateos Julieta L. , Sanchez Sabrina E , Legris Martina , Esteve-Bruna David , Torchio Jeanette C. , Petrillo Ezequiel , Goretti Daniela , Blanco-Touriñán Noel , Seymour Danelle K. , Schmid Markus , Weigel Detlef , Alabadí David , Yanovsky Marcelo J.
Published: June 2022

Plants undergo transcriptome reprogramming to adapt to daily and seasonal fluctuations in light and temperature conditions. While most efforts have focused on the role of master transcription factors, the importance of splicing factors modulating these processes is now emerging. Efficient pre-mRNA splicing depends on proper spliceosome assembly, which in plants and animals requires the methylosome complex. PICLN is part of the methylosome complex in both humans and Arabidopsis thaliana, and we show here that the human PICLN ortholog rescues phenotypes of A. thaliana picln mutants. Altered photomorphogenic and photoperiodic responses in A. thaliana picln mutants are associated with changes in pre-mRNA splicing, which partially overlap with those in prmt5 mutants. Mammalian PICLN also acts in concert with the Survival Motor Neuron (SMN) complex component GEMIN2 to modulate the late steps of UsnRNP assembly, and many alternative splicing events regulated by PICLN but not PROTEIN-ARGININE METHYL TRANSFERASE 5 (PRMT5), the main protein of the methylosome, are controlled by A. thaliana GEMIN2. As with GEMIN2 and SME1/PCP, low temperature, which increases PICLN expression, aggravates morphological and molecular defects of picln mutants. Taken together, these results establish a key role for PICLN in the regulation of pre-mRNA splicing and in mediating plant adaptation to daily and seasonal fluctuations in environmental conditions.