bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability
Authors: Bae Taejeong , Fasching Liana , Wang Yifan , Shin Joo Heon , Suvakov Milovan , Jang Yeongjun , Norton Scott , Dias Caroline , Mariani Jessica , Jourdon Alexandre , Wu Feinan , Panda Arijit , Pattni Reenal , Chahine Yasmine , Yeh Rebecca , Roberts Rosalinda C. , Huttner Anita , Kleinman Joel E. , Hyde Thomas M. , Straub Richard E. , Walsh Christopher A. ,   Brain Somatic Mosaicism Network§, Urban Alexander E. , Leckman James F. , Weinberger Daniel R. , Vaccarino Flora M. , Abyzov Alexej , Walsh Christopher A. , Park Peter J. , Sestan Nenad , Weinberger Daniel , Moran John V. , Gage Fred H. , Vaccarino Flora M. , Gleeson Joseph , Mathern Gary , Courchesne Eric , Roy Subhojit , Chess Andrew J. , Akbarian Schahram , Bizzotto Sara , Coulter Michael , Dias Caroline , D’Gama Alissa , Ganz Javier , Hill Robert , Huang August Yue , Khoshkhoo Sattar , Kim Sonia , Lee Alice , Lodato Michael , Maury Eduardo A. , Miller Michael , Borges-Monroy Rebeca , Rodin Rachel , Zhou Zinan , Bohrson Craig , Chu Chong , Cortes-Ciriano Isidro , Dou Yanmei , Galor Alon , Gulhan Doga , Kwon Minseok , Luquette Joe , Sherman Maxwell , Viswanadham Vinay , Jones Attila , Rosenbluh Chaggai , Cho Sean , Langmead Ben , Thorpe Jeremy , Erwin Jennifer , Jaffe Andrew , McConnell Michael , Narurkar Rujuta , Paquola Apua , Shin Jooheon , Straub Richard , Abyzov Alexej , Bae Taejeong , Jang Yeongjun , Wang Yifan , Molitor Cindy , Peters Mette , Linker Sara , Reed Patrick , Wang Meiyan , Urban Alexander , Zhou Bo , Zhu Xiaowei , Pattni Reenal , Serres Amero Aitor , Juan David , Lobon Irene , Marques-Bonet Tomas , Solis Moruno Manuel , Garcia Perez Raquel , Povolotskaya Inna , Soriano Eduardo , Antaki Danny , Averbuj Dan , Ball Laurel , Breuss Martin , Yang Xiaoxu , Chung Changuk , Emery Sarah B. , Flasch Diane A. , Kidd Jeffrey M. , Kopera Huira C. , Kwan Kenneth Y. , Mills Ryan E. , Moldovan John B. , Sun Chen , Zhao Xuefang , Zhou Weichen , Frisbie Trenton J. , Cherskov Adriana , Fasching Liana , Jourdon Alexandre , Pochareddy Sirisha , Scuderi Soraya
Published: July 2022

We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 with schizophrenia, and 59 with autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, brains had 20 to 60 detectable single-nucleotide mutations, but ~6% of brains harbored hundreds of somatic mutations. Hypermutability was associated with age and damaging mutations in genes implicated in cancers and, in some brains, reflected in vivo clonal expansions. Somatic duplications, likely arising during development, were found in ~5% of normal and diseased brains, reflecting background mutagenesis. Brains with autism were associated with mutations creating putative transcription factor binding motifs in enhancer-like regions in the developing brain. The top-ranked affected motifs corresponded to MEIS (myeloid ectopic viral integration site) transcription factors, suggesting a potential link between their involvement in gene regulation and autism.
In situ architecture of the ciliary base reveals the stepwise assembly of intraflagellar transport trains
Authors: van den Hoek Hugo , Klena Nikolai , Jordan Mareike A. , Alvarez Viar Gonzalo , Righetto Ricardo D. , Schaffer Miroslava , Erdmann Philipp S. , Wan William , Geimer Stefan , Plitzko Jürgen M. , Baumeister Wolfgang , Pigino Gaia , Hamel Virginie , Guichard Paul , Engel Benjamin D.
Published: July 2022

The cilium is an antenna-like organelle that performs numerous cellular functions, including motility, sensing, and signaling. The base of the cilium contains a selective barrier that regulates the entry of large intraflagellar transport (IFT) trains, which carry cargo proteins required for ciliary assembly and maintenance. However, the native architecture of the ciliary base and the process of IFT train assembly remain unresolved. In this work, we used in situ cryo–electron tomography to reveal native structures of the transition zone region and assembling IFT trains at the ciliary base in
Chlamydomonas
. We combined this direct cellular visualization with ultrastructure expansion microscopy to describe the front-to-back stepwise assembly of IFT trains: IFT-B forms the backbone, onto which bind IFT-A, dynein-1b, and finally kinesin-2 before entry into the cilium.
Pollinators of the sea: A discovery of animal-mediated fertilization in seaweed
Authors: Lavaut E. , Guillemin M.-L. , Colin S. , Faure A. , Coudret J. , Destombe C. , Valero M.
Published: July 2022

The long-held belief that animal-mediated pollination is absent in the sea has recently been contradicted in seagrasses, motivating investigations of other marine phyla. This is particularly relevant in red algae, in which female gametes are not liberated and male gametes are not flagellated. Using experiments with the isopod
Idotea balthica
and the red alga
Gracilaria gracilis
, we demonstrate that biotic interactions dramatically increase the fertilization success of the alga through animal transport of spermatia on their body. This discovery suggests that animal-mediated fertilization could have evolved independently in terrestrial and marine environments and raises the possibility of its emergence in the sea before plants moved ashore.
Constraints on the adjustment of tidal marshes to accelerating sea level rise
Authors: Saintilan Neil , Kovalenko Katya E. , Guntenspergen Glenn , Rogers Kerrylee , Lynch James C. , Cahoon Donald R. , Lovelock Catherine E. , Friess Daniel A. , Ashe Erica , Krauss Ken W. , Cormier Nicole , Spencer Tom , Adams Janine , Raw Jacqueline , Ibanez Carles , Scarton Francesco , Temmerman Stijn , Meire Patrick , Maris Tom , Thorne Karen , Brazner John , Chmura Gail L. , Bowron Tony , Gamage Vishmie P. , Cressman Kimberly , Endris Charlie , Marconi Christina , Marcum Pamela , St. Laurent Kari , Reay William , Raposa Kenneth B. , Garwood Jason A. , Khan Nicole
Published: July 2022

Much uncertainty exists about the vulnerability of valuable tidal marsh ecosystems to relative sea level rise. Previous assessments of resilience to sea level rise, to which marshes can adjust by sediment accretion and elevation gain, revealed contrasting results, depending on contemporary or Holocene geological data. By analyzing globally distributed contemporary data, we found that marsh sediment accretion increases in parity with sea level rise, seemingly confirming previously claimed marsh resilience. However, subsidence of the substrate shows a nonlinear increase with accretion. As a result, marsh elevation gain is constrained in relation to sea level rise, and deficits emerge that are consistent with Holocene observations of tidal marsh vulnerability.
Engineering defects with DNA
Authors: Wang YuHuang
Published: July 2022

Single-walled carbon nanotubes are structurally modified by using a genetic sequence
Structures of the nitrogenase complex prepared under catalytic turnover conditions
Authors: Rutledge Hannah L. , Cook Brian D. , Nguyen Hoang P. M. , Herzik Mark A. , Tezcan F. Akif
Published: July 2022

The enzyme nitrogenase couples adenosine triphosphate (ATP) hydrolysis to the multielectron reduction of atmospheric dinitrogen into ammonia. Despite extensive research, the mechanistic details of ATP-dependent energy transduction and dinitrogen reduction by nitrogenase are not well understood, requiring new strategies to monitor its structural dynamics during catalytic action. Here, we report cryo–electron microscopy structures of the nitrogenase complex prepared under enzymatic turnover conditions. We observe that asymmetry governs all aspects of the nitrogenase mechanism, including ATP hydrolysis, protein-protein interactions, and catalysis. Conformational changes near the catalytic iron-molybdenum cofactor are correlated with the nucleotide-hydrolysis state of the enzyme.
The material properties of chromatin in vivo
Authors: So Woong Young , Tanner Kandice
Published: July 2022

Chromatin is fluidlike within the crowded nucleus when probed in a living cell
Divergent Host-Microbe Interaction and Pathogenesis Proteins Detected in Recently Identified
Liberibacter
Species
Authors: Hansen Allison K. , Sanchez Ariana N. , Kwak Younghwan
Published: July 2022

“Candidatus”
(
Ca.
) Liberibacter taxa are economically important plant pathogens vectored by insects; however, these host-dependent bacterial taxa are extremely difficult to study because they are unculturable. Recently, we identified a new
Ca
.
Supplemental Material: Filling critical gaps in the space-time record of High Lava Plains and co-Columbia River Basalt Group rhyolite volcanism
Authors: Swenton Vanessa M. , et al.
Published: July 2022

(A) Referenced ages and sample locations; (B) Sources of pre-existing geochemical data; (C) 40Ar/39Ar ideograms and plateaus; (D) Detailed 40Ar/39Ar analysis sample preparation procedures and analytical methods; (E) Full argon data files—feldspar and groundmass analyzed at OSU; and (F) Full argon data files—biotite analyzed at OSU.
Paediatric acute respiratory distress syndrome: consider the role of lymphatics
Authors: Lu Mimi , Cavazzoni Elena , Selvadurai Hiran , Burren Juerg Martin
Published: July 2022

We present a case of a 7-day-old male infant with severe respiratory disease requiring venoarterial extracorporeal membrane oxygenation therapy with evidence of lymphangiectasia on lung biopsy. Differentiating primary versus secondary lymphangiectasis in this patient remains a riddle despite extensive investigations including an infective screen, lung biopsy and whole-genome sequencing. In addition to the standard therapies used in paediatric acute respiratory distress syndrome, such as lung-protective ventilation, permissive hypoxaemia and hypercarbia, nursing in the prone position, early use of muscle relaxants, rescue intravenous corticosteroids and broad-spectrum antibiotics, the patient was also given octreotide despite the absence of a chylothorax based on the theoretical benefit of altering the lymphatic flow. His case raises an interesting discussion around the role of lymphatics in the pathophysiology of paediatric and adult respiratory distress syndrome and prompts the exploration of novel agents which may affect lymphatic vessels used as an adjunctive therapy.
Importance of an echocardiogram in the evaluation of ataxia
Authors: Stokreef Sarah , Lemos Mariana , Quintas Sofia
Published: July 2022

We present the case of a boy in his middle childhood with gait ataxia and loss of reflexes with a 1-year onset. He had a background of an autism spectrum disorder but was otherwise healthy. A paediatric cardiology assessment was requested to investigate possible cardiac involvement associated to his neurological symptoms. Even though he had no cardiac symptoms and a normal electrocardiography, the echocardiogram revealed severe asymmetric left ventricle hypertrophy consistent with hypertrophic cardiomyopathy. This prompted genetic testing and the diagnosis of Friedreich’s ataxia was confirmed.
Postoperative dengue haemorrhagic shock and Trichosporon fungal sepsis: a multidisciplinary rescue
Authors: Sachan Ankit , Nayyar Rishi , Kumar Arvind , Rewari Vimi
Published: July 2022

A woman in her 30s had robotic pyeloplasty done for right ureteropelvic junction obstruction. Incidentally she developed dengue viral fever starting on postoperative day 1 itself, which progressed to dengue haemorrhagic shock by 1 week, complicating pyeloplasty due to pelvicalyceal haematoma. Dengue associated shock was superimposed with subsequent gram-negative bacterial sepsis, further complicated later with Trichosporon fungal sepsis. She was managed under multidisciplinary care, involving urology, infectious disease and ICU care. Her diagnostic and difficult management issues due to these rare sequential medical issues in an otherwise usually uncomplicated postsurgical phase are discussed along with short review of literature. This case highlights the importance of early diagnosis, timely supportive care and appropriate management in such tropical infections with significant associated mortality.
Role of corneal radius of curvature in early identification of fundus tessellation in children with low myopia
Authors: Gong Wei , Cheng Tianyu , Wang Jingjing , Zhang Bo , Chen Jun , Zhu Jianfeng , Zou Haidong , Liu Kun , He Xiangui , Xu Xun
Published: July 2022

Aim

To assess the role of the corneal radius of curvature (CR) in the identification of fundus tessellation in children with low myopia.

Methods

In the cross-sectional study, students aged 9–12 years from 24 primary schools in Shanghai were enrolled by cluster sampling. Participants underwent measurements including cycloplegic refraction and axial length. Fundus images and choroidal thickness were obtained by swept-source optical coherence tomography. Fundus tessellation was classified into four grades according to fundus photographs.

Results

A total of 1127 children with low myopia (spherical equivalence (SE) >−3.00 dioptre (D) but ≤−0.50 D) were included, with a mean age of 10.29±0.60 years and a mean SE of −1.44±0.69 D. Fundus tessellation was found in 591 (52.4%) cases (grade 1: 428, 38.0%; grade 2: 128, 11.4%; grade 3: 35, 3.1%). Choroidal thickness decreased as fundus tessellation grade increased (p trend <0.001). According to regression analysis, higher fundus tessellation grade was independently associated with larger CR (OR, 7.499; 95% CI 2.279 to 24.675, p=0.001). For those with CR >7.9 mm, along with CR, degree and proportion of fundus tessellation increased sharply.

Conclusion

Fundus tessellation existed in more than half of children with low myopia. Preliminary fundus photography conducted in children with low myopia with large CR would be necessary and beneficial to the early management of myopic fundus changes.

Trial registration numberNCT02980445.
Community-based doulas for migrant and refugee women: a mixed-method systematic review and narrative synthesis
Authors: Khaw Sarah Min-Lee , Zahroh Rana Islamiah , O'Rourke Kerryn , Dearnley Red , Homer Caroline , Bohren Meghan A
Published: July 2022

Background

Community-based doulas share the same cultural, linguistic, ethnic backgrounds or social experiences as the women they support. Community-based doulas may be able to bridge gaps for migrant and refugee women in maternity settings in high-income countries (HICs). The aim of this review was to explore key stakeholders’ perceptions and experiences of community-based doula programmes for migrant and refugee women during labour and birth in HICs, and identify factors affecting implementation and sustainability of such programmes.

Methods

We conducted a mixed-method systematic review, searching MEDLINE, CINAHL, Web of Science, Embase and grey literature databases from inception to 20th January 2022. Primary qualitative, quantitative and mixed-methods studies focusing on stakeholders’ perspectives and experiences of community-based doula support during labour and birth in any HIC and any type of health facility were eligible for inclusion. We used a narrative synthesis approach to analysis and GRADE-CERQual approach to assess confidence in qualitative findings.

Results

Twelve included studies were from four countries (USA, Sweden, England and Australia). There were 26 findings categorised under three domains: (1) community-based doulas’ role in increasing capacity of existing maternity services; (2) impact on migrant and refugee women’s experiences and health; and (3) factors associated with implementing and sustaining a community-based doula programme.

Conclusion

Community-based doula programmes can provide culturally-responsive care to migrant and refugee women in HICs. These findings can inform community-based doula organisations, maternity healthcare services and policymakers. Further exploration of the factors that impact programme implementation, sustainability, strategic partnership potential and possible wider-reaching benefits is needed.
Effect of less aggressive treatment on diabetic retinopathy severity scale scores: analyses of the RIDE and RISE open-label extension
Authors: Goldberg Roger A , Hill Lauren , Davis Tatiana , Stoilov Ivaylo
Published: July 2022

Objective

To evaluate factors associated with Diabetic Retinopathy Severity Scale (DRSS) changes with less frequent ranibizumab after induction therapy.

Methods and analysis

Post hoc analyses of RIDE/RISE and their open-label extension (OLE). Analyses included patients with diabetic retinopathy (DR)/diabetic macular oedema who completed the OLE. Comparisons were made between patients with improved/maintained (≥0 step decrease from OLE baseline (month 36) to month 48) versus worsened (≥1 step increase) DRSS during the OLE. DRSS changes over 12 months were compared between patients randomised to ranibizumab at RIDE/RISE baseline who improved to DRSS score ≤43 at OLE baseline (induced) versus those randomised to sham with DRSS score ≤43 at RIDE/RISE baseline (native).

Results

From OLE baseline to month 48, 72% (263/367) of patients improved/maintained DRSS scores. These patients had similar mean best-corrected visual acuity at RIDE/RISE (56.4 letters) and OLE baseline (68.6 letters) versus patients with worsened scores (58.2 and 70.8 letters). Patients who improved/maintained DRSS scores had similar mean central foveal thickness at RIDE/RISE (492 µm) and OLE baseline (196 µm) versus patients with worsened scores (441 and 167 µm). Patients who improved/maintained DRSS scores received a significantly higher (p<0.0001) mean number of pro re nata (PRN) injections (4.4) between OLE baseline and month 48 versus those with worsened scores (2.3). Patients with more severe DR at baseline who achieved mild-to-moderate non-proliferative DR (NPDR) induced by monthly ranibizumab injections were significantly more likely to worsen (p<0.0001) than those with mild-to-moderate NPDR at baseline randomised to sham injections (1.0-step versus 0.1-step worsening).

Conclusions

Most patients improved/maintained DRSS scores with less-than-monthly PRN ranibizumab. Some minimum treatment/monitoring may be necessary to maintain improvements after induction therapy.

Trial registration numbers

NCT00473382/NCT00473330.
Fuchs endothelial corneal dystrophy: current perspectives on diagnostic pathology and genetics—Bowman Club Lecture
Authors: Thaung Caroline , Davidson Alice E
Published: July 2022

Fuchs endothelial corneal dystrophy (FECD) was first described over a century ago. Since then, we have learnt much about its clinical manifestations, surgical and non-surgical treatment, microscopic appearance and pathogenesis. Over the past decade, significant advances have been made with respect to our understanding of FECD genetics. This progress now enables us to appreciate that FECD in fact describes multiple entities with distinct underlying genetic causes. For example, an early-onset and rare form of the disease has been attributed to missense mutations in theCOL8A2gene, whereas the vast majority of late-onset cases can be attributed to a non-coding repeat expansion within theTCF4gene.

FECD is one of the most common indications for corneal transplantation. In recent years, attention has turned to alternative treatment techniques that do not depend on donor tissue supply. The design and development of these non-surgical treatment approaches have benefited from increased knowledge of pathogenesis.

This review will cover our current knowledge about the histology and genetics of FECD, and how combining these interdisciplinary approaches might may improve diagnostic accuracy and aid the development of therapeutics for this common and visually disabling disease.
Optimising neonatal antiretroviral therapy using raltegravir: a qualitative analysis of healthcare workers’ and caregivers’ perspectives
Authors: Katirayi Leila , Stecker Carl , Andifasi Precious , Mushavi Angela , Tiwari Pradisha , Jakazi Chioniso , Maphosa Talent , Thorsen Viva , Murandu Mildrate , Gombakomba Gladys , Mungati More , Denoeud-Ndam Lise , Rivadeneira Emilia , Weber Rachel , Hrapcak Susan
Published: July 2022

Background

In 2020, Zimbabwe adopted the WHO’s recommendation to use raltegravir (RAL) granule-based regimens for treatment of neonates identified with HIV at the time of birth testing. This study explores the acceptability of RAL granules by caregivers and healthcare workers (HCWs).

Methods

Interviews were conducted with 15 caregivers and 12 HCWs from 8 health facilities in Zimbabwe participating in the introductory pilot of RAL granules treatment for newborns. Eligible caregivers included those who had administered RAL to their infant and attended either 8th or 28th day of life appointments. Caregivers of neonates recently initiated on RAL were selected through convenience sampling. Eligible HCWs who provided RAL preparation, administration instructions and support to caregivers of neonates on RAL for at least 3 months were recruited from the same facilities as the caregivers. Interview transcripts were coded and thematically analysed.

Results

Caregivers reported that their babies looked healthier after RAL initiation, with improved skin appearance and weight gain. Some caregivers wanted their child to remain on RAL beyond 28 days instead of switching regimens, as recommended by national guidelines. HCWs observed that RAL granules improved health outcomes compared with other regimens. HCWs reported challenges with caregivers understanding dosing instructions, measuring with a syringe, swirling and not shaking the medicine, discarding unused medication and following the changes in the dosing schedule and amount when RAL was initiated a few days after birth. HCWs stated that adequate counselling and repeat demonstrations were crucial to ensure that caregivers clearly understood RAL dosing and administration instructions. HCWs requested more standardised training targeting nurses with guidance on handling missed doses and clarification on mixing RAL granules with water and not breastmilk.

Conclusion

While feedback from caregivers and HCWs on RAL implementation was positive, barriers were also noted. Adequate training and sufficient instruction and support for caregivers would help to ensure that RAL granules are prepared, dosed and administered correctly.
Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of nonmelanoma skin cancer
Authors: Silk Ann W , Barker Christopher A , Bhatia Shailender , Bollin Kathryn B , Chandra Sunandana , Eroglu Zeynep , Gastman Brian R , Kendra Kari L , Kluger Harriet , Lipson Evan J , Madden Kathleen , Miller David M , Nghiem Paul , Pavlick Anna C , Puzanov Igor , Rabinowits Guilherme , Ruiz Emily S , Sondak Vernon K , Tavss Edward A , Tetzlaff Michael T , Brownell Isaac
Published: July 2022

Nonmelanoma skin cancers (NMSCs) are some of the most commonly diagnosed malignancies. In general, early-stage NMSCs have favorable outcomes; however, a small subset of patients develop resistant, advanced, or metastatic disease, or aggressive subtypes that are more challenging to treat successfully. Recently, immune checkpoint inhibitors (ICIs) have been approved by the US Food and Drug Administration (FDA) for the treatment of Merkel cell carcinoma (MCC), cutaneous squamous cell carcinoma (CSCC), and basal cell carcinoma (BCC). Although ICIs have demonstrated activity against NMSCs, the routine clinical use of these agents may be more challenging due to a number of factors including the lack of predictive biomarkers, the need to consider special patient populations, the management of toxicity, and the assessment of atypical responses. With the goal of improving patient care by providing expert guidance to the oncology community, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). The expert panel drew on the published literature as well as their own clinical experience to develop recommendations for healthcare professionals on important aspects of immunotherapeutic treatment for NMSCs, including staging, biomarker testing, patient selection, therapy selection, post-treatment response evaluation and surveillance, and patient quality of life (QOL) considerations, among others. The evidence- and consensus-based recommendations in this CPG are intended to provide guidance to cancer care professionals treating patients with NMSCs.
Overcoming resistance to αPD-1 of MMR-deficient tumors with high tumor-induced neutrophils levels by combination of αCTLA-4 and αPD-1 blockers
Authors: Nebot-Bral Laetitia , Hollebecque Antoine , Yurchenko Andrey A , de Forceville Louise , Danjou Mathieu , Jouniaux Jean-Mehdi , Rosa Reginaldo C A , Pouvelle Caroline , Aoufouchi Said , Vuagnat Perrine , Smolenschi Cristina , Colomba Emeline , Leary Alexandra , Marabelle Aurelien , Scoazec Jean-Yves , Cassard Lydie , Nikolaev Sergey , Chaput Nathalie , Kannouche Patricia
Published: July 2022

Background

Clinical studies have highlighted the efficacy of anti-programmed death 1 (αPD-1) monoclonal antibodies in patients with DNA mismatch repair-deficient (MMRD) tumors. However, the responsiveness of MMRD cancers to αPD-1 therapy is highly heterogeneous, and the origins of this variability remain not fully understood.

Methods

4T1 and CT26 mouse tumor cell lines were inactivated for the MMRD geneMsh2,leading to a massive accumulation of mutations after serial passages of cells. Insertions/deletion events and mutation load were evaluated by whole exome sequencing. Mice bearing highly mutated MMRD tumor or parental tumors were treated with αPD-1 and tumor volume was monitored. Immune cell type abundance was dynamically assessed in the tumor microenvironment and the blood by flow cytometry. Neutrophils were depleted in mice using αLY6G antibody, and regulatory T (Treg) cell population was reduced with αCD25 or anti-cytotoxic T-lymphocytes-associated protein 4 (αCTLA-4) antibodies. Patients with MMRD tumors treated with immune checkpoint blockade-based therapy were retrospectively identified and neutrophil-to-lymphocyte ratio (NLR) was evaluated and examined for correlation with clinical benefit.

Results

By recapitulating mismatch repair deficiency in different mouse tumor models, we revealed that elevated circulating tumor-induced neutrophils (TIN) in hypermutated MMRD tumors hampered response to αPD-1 monotherapy. Importantly, depletion of TIN using αLy-6G antibody reduced Treg cells and restored αPD-1 response. Conversely, targeting Treg cells by αCD25 or αCTLA-4 antibodies limited peripheral TIN accumulation and elicited response in αPD-1-resistant MMRD tumors, highlighting a crosstalk between TIN and Treg cells. Thus, αPD-1+αCTLA-4 combination overcomes TIN-induced resistance to αPD-1 in mice bearing MMRD tumors. Finally, in a cohort of human (high microsatellite instability)/MMRD tumors we revealed that early on-treatment change in the NLR ratio may predict resistance to αPD-1 therapy.

Conclusions

TIN countered αPD-1 efficacy in MMRD tumors. Since αCTLA-4 could restrict TIN accumulation, αPD-1+αCTLA-4 combination overcomes αPD-1 resistance in hosts with hypermutated MMRD tumors displaying abnormal neutrophil accumulation.
Trends in characteristics of neurologists who provide stroke consultations in the USA, 2008–2021
Authors: Nakamoto Carter H , Wilcock Andrew D , Schwamm Lee H , Majersik Jennifer J , Zachrison Kori S , Mehrotra Ateev
Published: July 2022

Introduction

Patients with acute ischaemic strokes (AIS), on average, fare better with timely neurologist consultation, and a growing proportion of them receive one. However, little is known about trends in the characteristics of neurologists who treat AIS.

Methods

We identified AIS and transient ischaemic attack (TIA) episodes with neurologist consults in fee-for-service Medicare from January 2008 to September 2021. For each episode, we determined whether the neurologist was a vascular neurologist, was a high-volume provider, whether the patient was transferred between hospitals and the distance between the patient’s home and physician’s practice.

Results

From 2008 to 2021, the share of AIS/TIA episodes (n=5 073 294) with neurologist consults increased (52.9% to 61.7%). Among episodes with consults, the fraction conducted by a vascular neurologist (5.2% to 13.7%) or by a high-volume neurologist (13.2% to 14.9%) also increased. The fraction with the patient’s home and neurologist greater than 100 miles apart (4.8% to 9.6%) or in different states (5.1% to 8.1%) increased, as did the fraction with transfers (4.2% to 8.5%).

Discussion

Over the study period, the proportion of AIS/TIA episodes with consultations from neurologists with either vascular neurology certifications or high volumes increased substantially.
Ex utero intrapartum therapy in infants with congenital diaphragmatic hernia: a propensity score matching analysis
Authors: Zhao Yunlong , Wang Ying , Liu Chao , Jiang Yulin , Wei Yandong , Meng Hua , Jian Shan , Zhu Xiting , Pei Lijian , Bai Xiaochen , Feng Feng , Lv Yan , Zhou Xiya , Qi Qingwei , Li Jingna , Ma Lishuang
Published: July 2022

Objective

Previous studies have shown that ex utero intrapartum therapy (EXIT) is safe and feasible for newborns with congenital diaphragmatic hernia (CDH). This study reports our experience with EXIT in fetuses with CDH in an attempt to explore the efficacy of EXIT on the survival rate of this population.

Methods

A retrospective analysis of the clinical data of 116 children with CDH was conducted. The children were assigned to EXIT and non-EXIT groups. Propensity score matching (PSM) toward clinical data was performed, and the clinical characteristics and outcomes were compared. Taking survival at discharge as the main outcome, logistic regression analysis was carried out to explore the efficacy of EXIT on survival.

Results

During the study period, 30 of 116 children received EXIT. After PSM, the survival rates of the EXIT group and the non-EXIT group were 82.76% (24/29) and 48.28% (14/29), respectively (p=0.006). EXIT (OR=0.083, 95% CI=0.013to 0.525, p=0.008), liver herniation (OR=16.955, 95% CI=2.342 to 122.767, p=0.005), and gestational age at diagnosis (OR=0.662, 95% CI=0.497 to 0.881, p=0.005) were independent mortality-related risk factors of all children with CDH. Ninety-nine of 116 children underwent surgery. After PSM, the postoperative survival rates of the EXIT group and non-EXIT group were 84.6% (22/26) and 76.9% (20/26), respectively (p=0.754). Liver herniation (OR=10.451, 95% CI=1.641 to 66.544, p=0.013) and gestational age at diagnosis (OR=0.736, 95% CI=0.577 to 0.938, p=0.013) were independent mortality-related risk factors of children after surgery.

Conclusion

EXIT can be performed safely for selected prenatally diagnosed CDH neonates with potentially better survival and does not cause more maternal complications compared with traditional cesarean section.
A General Methodology to Optimize Flagged Constant Addition
Authors: Bhure Aroondhati , Smriti P. , Dhanote Vinay , Anil Kumar Uppugunduru , Ahmed Syed Ershad
Published: July 2022

Addition is a ubiquitous operation frequently carried out in most computing applications. Traditionally, three-operand addition is done using either two adders or a carry–save adder. However, there exist applications such as digital signal processing, image processing, floating point arithmetic, etc. wherein among the three operands, one is constant. For such cases, we propose a flagged constant addition methodology, applicable to any constant, to compute the result with the least area, delay and power. The resulting architecture is referred to as general constant flagged adder (GCFA). We propose an Optimized Constant Generation (OCG) algorithm and a Hardware Optimization Algorithm (HOA) to achieve hardware-efficient constant flagged adder. These two algorithms are designed to lower the computational complexity. The OCG algorithm accepts the constant to be added and converts it into an optimized constant. This optimized constant then forms the input to the HOA where the hardware modifications are performed. Unlike the proposed work, the existing flagged adder structures do not provide a general methodology to obtain the optimized constant and hardware for all the constants, resulting from the presence of architectural customization for all constants and word lengths. Exhaustive hardware analyses have been carried out to prove the efficacy of the proposed architecture against the existing designs. Structural Verilog code is synthesized for each to obtain the area, delay and power. Synthesis results show up to 35.85% and 49.24% reductions in area–delay and power–delay products, respectively. The improved speed and lower hardware requirements make the proposed methodology a suitable choice for constant addition.
An Improved Long Short-Term Memory Neural Network Wind Power Forecast Algorithm Based on TEMD Noise Reduction
Authors: You Hong , Li Zhixiong , Chen Xiaolei , Huang Lingxiang , Huang Feng
Published: July 2022

To accurately predict the wind power and adopt methods to balance the fluctuation of power grid, an improved long short-term memory (LSTM) neural network wind power forecast algorithm based on noise reduction by threshold empirical modal decomposition (TEMD) is proposed. First, the actual operation and maintenance data of wind farms are normalized and divided into a training set and a test set. Then, an LSTM structure is designed and a Sub-Grid Search (SGS) algorithm is proposed to optimize the hyperparameters of the LSTM network. Finally, the power data are decomposed and noise-reduced using TEMD is improved by the variable-point technique and the TEMD-LSTM power forecast model is constructed to predict the power in time. The predicted values obtained are restored and evaluated by the original size. The results show that compared with five other algorithms of the same kind, the proposed algorithm in this paper has a root mean square error (RMSE) of 30.40, a trend accuracy (TA) value of 67.23% and a training time of 886 s, with the best overall performance.
COVID-19 Classification Using Medical Image Synthesis by Generative Adversarial Networks
Authors: Nandhini Abirami R. , Durai Raj Vincent P. M. , Rajinikanth Venkatesan , Kadry Seifedine
Published: July 2022

The outbreak of novel coronavirus disease 2019, also called COVID-19, in Wuhan, China, began in December 2019. Since its outbreak, infectious disease has rapidly spread across the globe. The testing methods adopted by the medical practitioners gave false negatives, which is a big challenge. Medical imaging using deep learning can be adopted to speed up the testing process and avoid false negatives. This work proposes a novel approach, COVID-19 GAN, to perform coronavirus disease classification using medical image synthesis by a generative adversarial network. Detecting coronavirus infections from the chest X-ray images is very crucial for its early diagnosis and effective treatment. To boost the performance of the deep learning model and improve the accuracy of classification, synthetic data augmentation is performed using generative adversarial networks. Here, the available COVID-19 positive chest X-ray images are fed into the styleGAN2 model. The styleGAN model is trained, and the data necessary for training the deep learning model for coronavirus classification is generated. The generated COVID-19 positive chest X-ray images and the normal chest X-ray images are fed into the deep learning model for training. An accuracy of 99.78% is achieved in classifying chest X-ray images using CNN binary classifier model.
A Modified Deep Convolution Siamese Network for Writer-Independent Signature Verification
Authors: Jain Vanita , Gupta Prakhar , Chaudhry Aditya , Batra Manas , Hemanth D. Jude
Published: July 2022

In this paper problem of offline signature verification has been discussed with a novel high-performance convolution Siamese network. The paper proposes modifications in the already existing convolution Siamese network. The proposed method makes use of the Batch Normalization technique instead of Local Response Normalization to achieve better accuracy. The regularization factor has been added in the fully connected layers of the convolution neural network to deal with the problem of overfitting. Apart from this, a wide range of learning rates are provided during the training of the model and optimal one having the least validation loss is used. To evaluate the proposed changes and compare the results with the existing solution, our model is validated on three benchmarks datasets viz. CEDAR, BHSig260, and GPDS Synthetic Signature Corpus. The evaluation is done via two methods firstly by Test-Train validation and then by K-fold cross-validation (K = 5), to test the skill of our model. We show that the proposed modified Siamese network outperforms all the prior results for offline signature verification. One of the major advantages of our system is its capability of handling an unlimited number of new users which is the drawback of many research works done in the past.
A Study of Human–AI Symbiosis for Creative Work: Recent Developments and Future Directions in Deep Learning
Authors: Mahmud Bahar , Hong Guan , Fong Bernard
Published: July 2022

Recent advances in Artificial Intelligence (AI), particularly deep learning, are having an enormous impact on our society today. Record numbers of jobs previously held by people have been automated, from manufacturing to transportation to customer services. The concerns of AI replacing humans by taking over people's jobs need to be urgently addressed. This article investigates some promising different directions of AI development: Instead of using AI to replace people, we should use AI to team up with people so that both can work better and smarter. Human–AI symbiosis refers to people and AI working together to jointly solve problems and perform specific tasks. The recent developments in deep learning models and frameworks have significantly improved the efficiency and performance of human and AI collaborations. In this article, some research work on human–AI collaborative environments has been extensively studied and analyzed to reveal the progress in this field. Although the teaming of humans and machines includes many complex tasks, the development has been very promising. One of the main goals in this field is to develop additional capabilities in machines capable of being successful teammates with a human partner. The correctness of the outcomes is often determined by the underlying technology and how performance and human satisfaction are measured through the collaborative nature of the system. We conclude that the teaming of humans and AI, particularly deep learning, has the advantage of combining the power of AI with the human domain expertise to improve performance and create value. Human–AI symbiosis could be a promising future direction for AI's continuing integration into the world.
Recent Advances in Ciliate Biology
Authors: Howard-Till Rachel A. , Kar Usha Pallabi , Fabritius Amy S. , Winey Mark
Published: July 2022

Ciliates are a diverse group of unicellular eukaryotes that vary widely in size, shape, body plan, and ecological niche. Here, we review recent research advances achieved with ciliate models. Studies on patterning and regeneration have been revived in the giant ciliate Stentor, facilitated by modern omics methods. Cryo-electron microscopy and tomography have revolutionized the structural study of complex macromolecules such as telomerase, ribozymes, and axonemes. DNA elimination, gene scrambling, and mating type determination have been deciphered, revealing interesting adaptations of processes that have parallels in other kingdoms of life. Studies of common eukaryotic processes, such as intracellular trafficking, meiosis, and histone modification, reveal conservation as well as unique adaptations in these organisms that are evolutionarily distant from other models. Continual improvement of genetic and molecular tools makes ciliates accessible models for all levels of education and research. Such advances open new avenues of research and highlight the importance of ciliate research.
First Principles Determination of the Potential-of-Zero-Charge in an Alumina-Coated Aluminum/Water Interface Model for Corrosion Applications
Authors: Leung Kevin
Published: July 2022

The surfaces of most metals immersed in aqueous electrolytes have a several-nanometer-thick oxide/hydroxide surface layer. This gives rise to the existence of both metal∣oxide and oxide∣liquid electrotlyte interfaces, and makes it challenging to correlate atomic length-scale structures with electrochemical properties such the potential-of-zero-charge (PZC). The PZC has been shown to be correlated the onset potential for pitting corrosion. In this work, we conduct large-scale Density Functional Theory and ab initio molecular dynamics to calculate the PZC of a Al(111)∣γ-Al2O3(110)∣ water double-interface model within the context of aluminum corrosion. By partitioning the multiple interfaces involved into binary components with additive contributions to the overall work function and voltage, we predict the PZC to be −1.53 V vs SHE for this model. We also calculate the orbital energy levels of defects like oxygen vacancies in the oxide, which are critical parameters in theories associated with pitting corrosion. We predict that the Fermi level at the PZC lies above the impurity defect levels of the oxygen vacancies, which are therefore uncharged at the PZC. From the PZC estimate, we predict the voltage needed to create oxygen vacancies with net postive charges within a flatband approximation.
Six logical steps that connect the introduction of the Nernst equation to its clinical application
Authors: Ngo Han G. , Dandu Chaitu , Gibney Brianna L. , Kuang Serena Y.
Published: July 2022

This article fills the gaps in teaching about the Nernst equation, which is important in medical physiology. Six logical steps are presented that connect the introduction of the equation to its clinical applications to hyperkalemia and hypokalemia, two conditions that can be life-threatening if left untreated. Only when students know how to apply the equation will their learning transition from surface to mastery.
Systematic Construction and Validation of a Novel Ferroptosis-Related Gene Model for Predicting Prognosis in Cervical Cancer
Authors: Qin Wentao , He Can , Jiang Daqiong , Gao Yang , Chen Yu , Su Min , Yang Yuanjun , Yang Zhao , Cai Hongbing , Wang Hua
Published: July 2022

Background and Purpose. Ferroptosis, a mechanism of cell death that is iron-dependent, participates in various pathologies of cancer (CC). Nevertheless, the specific function that ferroptosis plays in the onset and progression of cervical cancer (CC) is yet uncertain. This research sought to examine the value of ferroptosis-related genes (FRGs) in the progression and prognosis of CC. Methods. Datasets containing RNA sequencing and corresponding clinical data of cervical cancer patients were obtained from searching publicly accessible databases. The “NMF” R package was conducted to calculate the matrix of the screened prognosis gene expression. Ferroptosis-related differential genes in cervical cancer were detected using the “limma” R function and WGCNA. The least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression analysis were conducted to develop a novel prognostic signature. The prediction model was verified by the nomogram integrating clinical characteristics; the GSE44001 dataset was used as an external verification. Then, the immune status and tumor mutation load were explored. Finally, immunohistochemistry as well as quantitative polymerase chain reaction (RT-qPCR) was utilized to ascertain the expression of FRGs. Results. Two molecular subgroups (cluster 1 and cluster 2) with different FRG expression patterns were recognized. A ferroptosis-related model based on 4 genes (VEGFA, CA9, DERL3, and RNF130) was developed through TCGA database to identify the unfavorable prognosis cases. Patients in cluster 1 showed significantly decreased overall survival in contrast with those in cluster 2 (

P
<
0.05

). The LASSO technique and Cox regression analysis were both utilized to establish the independence of the prognostic model. The validity of nomogram prognostic predictions has been well demonstrated for 3- and 5-year survival in both internal and external data validation cohorts. These two subgroups showed striking differences in tumor-infiltrating leukocytes and tumor mutation burden. The low-risk subgroup showed a longer overall survival time with a higher immune cell score and higher tumor mutation rate. Gene functional enrichment analyses revealed predominant enrichment in various tumor-associated signaling pathways. Finally, the expression of each gene was confirmed by immunohistochemistry and RT-qPCR. Conclusion. A novel and comprehensive ferroptosis-related gene model was proposed for cervical cancer which was capable of distinguishing the patients independently with high risk for poor survival, and targeting ferroptosis may represent a promising approach for the treatment of CC.
Life-Threatening Coronary Vasospasm Treated by Implantable Cardioverter Defibrillator: The Warning Signs
Authors: Adepoju Deborah , Smith Jamie A. L. , Leslie Stephen J.
Published: July 2022

Coronary artery vasospasm is the sudden narrowing of an artery caused by rapid prolonged contraction. It reduces blood supply to the heart and can present with typical cardiac chest pain symptoms. Vasospasm can lead to fatal arrhythmic complications such as ventricular fibrillation. Our case report describes an example of this occurring in a 53-year-old female, and the management plan that ensued. We look at the importance of accurate and prompt diagnosis of vasospasm and how this can have implications for treatment options. One of the available treatments for vasospasm is placement of an implantable cardioverter defibrillator (ICD). This delivers a shock in the event of future life-threatening arrhythmia, with the aim of preventing cardiac arrest. ICD placement, however, is not always a suitable option. This case report discusses the various challenges that arose while making the decision for ICD placement and gives insight into the best available treatment options for coronary artery vasospasm. We also highlight early warning signs that predict life-threatening vasospastic events and how this can be diagnosed and treated appropriately.
Thermodynamic Characteristics of CH4 Adsorption on Shale at Different Temperatures
Authors: Xue Pei , Liang Quansheng , Hao Shiyan , Yin Jintao , Gao Chao , Zhang Lixia , Zhao Qianping
Published: July 2022

In order to clarify the effect of temperature on the isosteric heat of adsorption of CH4 onto shale, by using the isothermal adsorption data of shale in the temperature range of 300~473 K and the pressure range of 0.08~14 MPa, the isosteric heat of adsorption is calculated, respectively, in the temperature range of 300~308 K, 338~373 K, and 423~473 K. The results show that the influence of temperature on the isosteric heat of adsorption of CH4 onto shale is mainly reflected in three aspects: the variation range of the isosteric heat of adsorption, the absolute adsorption capacity at which the isosteric heat of adsorption reach the maximum, and the change rate of the isosteric heat of adsorption. Specifically, as the temperature range moves to a higher range, the variation range of the isosteric heat increases significantly, and the absolute adsorption capacity decreases. The curve shape of the change rate of the isosteric heat of adsorption in different temperature ranges remained the same (decreased first and then increased), but the change rate increased gradually as the temperature range moved to a higher temperature range.