bluuebunny/crossref_metadata_2025 huggingface dataset:
Spring Extreme Precipitation Days in North China and Their Reliance on Atmospheric Circulation Patterns during 1979–2019
Authors: Xu Jun , Zhang Qinghong , Bi Baogui , Chen Yun
Published: January 2022

The interannual variation of springtime extreme precipitation (SEP) days in North China (NC) and their reliance on atmospheric circulation patterns are studied by using the continuous daily record of 396 rain gauges and the fifth generation of the European Centre for Medium-Range Weather Forecasts atmospheric reanalysis during 1979–2019. The SEP days are defined as the days when at least 10% of rain gauges in NC record daily precipitation no less than 10.5 mm. Results show that the number of SEP days shows large interannual variability but no significant trend in the study period. Using the objective classification method of the obliquely rotated principal analysis in T-mode, we classify the atmospheric circulation into five different patterns based on the geopotential height at 700 hPa. Three circulation patterns all have fronts and are associated with strong southerly wind, leading to 88% of SEP days in NC. The strong southerly wind may provide moisture and dynamic forcing for the frontal precipitation. The interannual variation of SEP days is related with the number of the three above-mentioned dominant circulation patterns. Further analysis shows that the West Pacific pattern could be one of the possible climate variability modes related to SEP days. This study reveals that the daily circulation pattern may be the linkage between SEP days and climate variability modes in NC.

Significance Statement

Springtime extreme precipitation (SEP) has important social and economic impacts on North China (NC), but few studies have examined the variation of SEP in NC. We find that the number of SEP days has no significant trend but shows large interannual variability during 1979–2019. The interannual variation of SEP days is mainly determined by the total days of three frontal circulation patterns associated with strong southerly wind. Based on the daily circulation pattern, the West Pacific pattern is found to be one of the possible climate variability modes related to SEP days. These findings may shed light on the understanding of SEP in midlatitudes around the world.
Examining the Factors Influencing Applicants’ Placement on One General Surgery Program’s Rank Order List
Authors: Hahn Alexandra , Gorham Jessica , Mohammed Alaa , Strollo Brian , Fuhrman George
Published: January 2022

Purpose

Surgery residency applications include variables that determine an individual’s rank on a program’s match list. We performed this study to determine which residency application variables are the most impactful in creating our program’s rank order list.

Methods

We completed a retrospective examination of all interviewed applicants for the 2019 match. We recorded United States Medical Licensing Examinations (USMLE) step I and II scores, class quartile rank from the Medical Student Performance Evaluation (MSPE), Alpha Omega Alpha (AOA) membership, geographic region, surgery clerkship grade, and grades on other clerkships. The MSPE and letters of recommendation were reviewed by two of the authors and assigned a score of 1 to 3, where 1 was weak and 3 was strong. The same two authors reviewed the assessments from each applicant’s interview and assigned a score from 1-5, where 1 was poor and 5 was excellent. Univariate analysis was performed, and the significant variables were used to construct an adjusted multivariate model with significance measured at P < .05.

Results

Univariate analysis for all 92 interviewed applicants demonstrated that USMLE step 2 scores ( P = .002), class quartile rank ( P = .004), AOA status ( P = .014), geographic location ( P < .001), letters of recommendation ( P < .001), and interview rating ( P < .001) were significant in predicting an applicant’s position on the rank list. On multivariate analysis only USMLE step 2 ( P = .018) and interview ( P < .001) remained significant.

Conclusion

USMLE step 2 and an excellent interview were the most important factors in constructing our rank order list. Applicants with a demonstrated strong clinical fund of knowledge that develop a rapport with our faculty and residents receive the highest level of consideration for our program.
The Unspeakable Nature of Death & Dying During Childhood: A Silenced Phenomenon in Pediatric Care
Authors: Campbell Sydney , Moola Fiona J. , Gibson Jennifer L. , Petch Jeremy , Denburg Avram
Published: January 2022

In pediatric settings, the concept of hope is frequently positioned as a fundamental aspect of care and at odds with the possibility and proximity of death. This arguably fosters silence about death and dying in childhood despite evidence indicating the benefits of open communication at the end of life. In this paper, we describe the unspeakable nature of death and dying in childhood, including its conceptual and clinical causes and dimensions, its persistence, and the associated challenges for children and youth facing critical illnesses, their families, and society. We explore how the tension between hope and death can be reframed and apply our analysis to the context of medical assistance in dying for mature minors in Canada. Considering the lack of related literature, this paper offers initial reflections to form a framework for the unspeakable nature of death and dying in childhood and to advance the crucial need for research.
Jayaprakash Narayan and Indira Gandhi, 1966–74: Before the Rivalry
Authors: Ankit Rakesh
Published: January 2022

When the Gandhian Jayaprakash Narayan (JP) gave the clarion call of Total Revolution, Prime Minister Indira Gandhi responded heavy-handedly by imposing the Emergency in India in 1974–5. This all-encompassing duel has dominated politics and political scholarship since. Their domestic clash has established many analytical prisms for the contemporary public sphere in India, particularly personality politics versus people’s power, single party versus coalition grouping, electoral democracy versus authoritarian dictatorship, and student/youth movements versus generational status quo. Simultaneously, it has also highlighted their differences in a way that has served to bury their affinities and agreements—not only on obscure matters. This article seeks to soften this dichotomy on the basis of their correspondence, and complemented by other primary material, to sketch their consensus in an earlier period. It shows that before their break, the socialist JP and the statist Indira Gandhi exhibited complementary stands on national issues regarding Nagaland, Kashmir and Bangladesh. This national nearness complicates their later adversarial politics on domestic issues, adds dimension to our understanding of the mid-1960s and mid-1970s, and contributes to contemporary understandings of their respective places in narratives of the state against society in India.
WhatsApp Generation in Zoom University: Online Pedagogical Challenges and Innovations
Authors: Aggarwal Divya , Elembilassery Varun
Published: January 2022

Management education has undergone significant changes owing to the COVID-19 pandemic. The classroom delivery has moved from an offline mode to a completely online mode, unravelling many pedagogical challenges and constraints. This study explores the pedagogical challenges faced by academicians and the innovative remedial measures adopted by them. This study follows an inductive approach using qualitative interviews and uses the cognitive apprenticeship model as the theoretical underpinning. Findings indicate that all domain aspects of the cognitive apprenticeship model are not equally relevant in an online teaching scenario compared to offline teaching. Findings also indicate that the interpersonal and communicational aspects of the learning environment have gained more prominence in online teaching. This article contributes to the existing literature by bringing early evidence on the challenges and innovations in online teaching. In addition, this study also contributes to the understanding of the cognitive apprenticeship model in an online scenario. Even though the scope of the study was limited to academicians from the finance and accounting area, the findings are globally relevant. They have practical implications for other disciplines as well.

JEL Codes: M0, I20, I29, Y7
Role of micro-RNA132 and its long non coding SOX2 in diagnosis of lupus nephritis
Authors: Ahmed Rasha F , Shaker Olfat Gamil , abdelghany Hend M , Helmy Abdallah Nilly , Elsayed Samar Hisham , Kamel Bothina Ahmed
Published: January 2022

Background

The skin and the kidney are commonly affected in systemic lupus erythematosus (SLE) with similar molecular mechanisms. Although clinical indicators of renal injury in SLE are fairly uncontroversial, few biomarkers are reliable. The role of micro-RNAs (mi-RNAs) in lupus nephritis (LN) pathogenesis has been investigated to help in early diagnosis.

Purpose

The aim of work is to evaluate miRNA132 and SOX2 expressions in SLE Egyptian patients; with and without nephritis, and the relation between miRNA132 and its long non-coding gene SOX2 in both patients groups.

Research Design

This is a case-control study involving 100 SLE patients with and without LN (LN and non-LN groups), and 50 age-and sex-matched healthy controls. The study was carried out to detect miRNA132 and SOX2 expression by quantitative Real-Time Polymerase chain reaction methods. The SLE disease activity index (SLEDAI) was assessed.

Results

SLEDAI increased in LN compared to non-LN. Micro-RNA132 expression was significantly increased in patient groups compared to controls ( p<0.01) and increased in LN more than non-LN group ( p<0.001). SOX2 significantly decreased in patient groups compared to controls ( p<0.001), and was more in LN compared to non-LN group ( p<0.001). There was a negative correlation between miRNA132 and SOX2 expression in both patient groups ( p<0.001).

Conclusion

miRNA132 and SOX2 may play a role in SLE activity and help in the early non-invasive diagnosis of LN.
The Tamil Issue in India–Sri Lanka Relationships: Priorities and Interests
Authors: Ranjan Amit , Chattoraj Diotima
Published: January 2022

More than 25 years of ethnic war in Sri Lanka ended in 2009. Expressing ‘serious concerns’ on human rights situation in post-civil war Sri Lanka, the United Nations Human Rights Council (UNHRC) has adopted critical resolutions. The eighth such resolution was adopted in March 2021. India abstained for the second time from voting on a resolution against Sri Lanka at the UNHRC since 2014. In 2012 and 2013, India voted in favour of resolutions that have been critical of Sri Lanka. This article, examines the shift in India’s approach towards the Tamil issue in Sri Lanka.
A New Score for Determining Thrombus Burden in STEMI Patients: The MAPH Score
Authors: Abacioglu Ozge Ozcan , Yildirim Arafat , Karadeniz Mine , Abacioglu Serkan , Koyunsever Nermin Yildiz , Dindas Ferhat , Dogdus Mustafa , Kaplangoray Mustafa
Published: January 2022

Aim

to investigate whether the MAPH score, which is a new score that combines blood viscosity biomarkers such as mean platelet volume (MPV), total protein and hematocrit, can be used to predict thrombus burden in ST-segment elevation myocardial infarction (STEMI) patients.

Methods

A total of 473 consecutive patients with STEMI were included in the study. Intracoronary tirofiban/abciximab infusion was applied to patients with thrombus load ≥3 and these patients (n = 71) were defined as the patient group with high thrombus load. MPV, age, hematocrit and total protein values of the patients were recorded. High shear rate (HSR) and low shear rate (LSR) were calculated from total protein and hematocrit values. Cut-off values were determined for high thrombus load by using Youden index, and score was determined as 0 or 1 according to cut-offs. The sum of the scores was calculated as the MAPH score.

Results

The mean age of the patients included in the study was 59.6 ± 12.6 (n = 354 male, 74.8%). There was no difference between the groups in terms of gender, HT and DM ( P = .127, P = .402 and P = .576, respectively). In the group with high thrombus load; total protein, MPV and hematocrit values were higher ( P < .001, P = .001 and P = .03, respectively). Comparison of receiver operating characteristic (ROC) curve analysis revealed that the MAPH score had better performance in predicting higher thrombus load than both other self-containing parameters and HSR and LSR.

Conclusion

The MAPH score may be a new score that can be used to determine thrombus burden in STEMI patients.
Experimental investigation on behavior of splicing glass fiber–reinforced polymer-concrete–steel double-skin tubular columns under axial compression
Authors: Li Xue , Wang Lian-guang , Gao Hai-yang , Zhang Ni
Published: January 2022

Splicing glass fiber–reinforced polymer (GFRP)-concrete–steel double-skin tubular column (DSTC) is to set connection component at the joint of two or more separated GFRP tubes, and then pour concrete in the double-tube interlayer to form a continuous composite member. In this paper, the splicing DSTC composite members based on steel bar connection were designed and tested under axial compression to determine its mechanical performance. The main parameters include the connection steel ratio, the hollow ratio, and the thickness of GFRP tube. The results show that the GFRP tube presents apparent constraint effect on the concrete at about 60% of the ultimate load. The failure of splicing specimen occurred in the non-splicing section at a certain distance from the splice joint, and the stirrups at the splice joint provide effective constraint effect on the internal concrete. The proposed DSTC splicing method based on steel cage connection can satisfy the strength requirements of splice joint. Nevertheless, the increase of axial steel bar ratio cannot improve the bearing capacity of the splicing column, and the steel ratio of 2.44% is suggested for the splice joint of DSTCs under axial compression. The axial bearing capacity of splicing DSTCs significantly increases with the increase of GFRP tube thickness, but the amount of stirrups should be increased properly when a larger tube thickness is used. Two models were selected to calculate the bearing capacity of splicing members and it is found that Yu’s model is more accurate in predicting splicing DSTCs.
Deformation properties of arched glass fiber reinforced plastics structure under static load: Considering the soil cover and rise-span ratio
Authors: Liu Shu-Yan , Zhang Zhao-Yang , Xue Xiao , Wang Qing-Zhou , Xiao Cheng-Zhi
Published: January 2022

In this study, the load level, soil cover height, rise-span ratio, and arch foot constraint state were utilized to explore the mechanical properties of buried arch glass fiber reinforced plastics (GFRP) structures. Through the indoor scale-down test, the stress and deformation of arched GFRP structures under different load and soil cover height were investigated. Additionally, through the three-dimensional finite element method, the influence of the rise-span ratio and the constraint state of arch foot on the mechanical properties were obtained. The results indicate the new buried composite arch structure has excellent bearing capacity for the possible traffic load. Simultaneously, the semi-elliptical arch structure was believed to outperform the semi-circular arch structure when considering the external load. Specifically, increasing the soil cover height and reducing rise-span ratio were found to achieve the load-reduction effect.
Fiber Optic RealShape (FORS) Technology for Endovascular Navigation in Severe Tortuous Vessels
Authors: Panuccio Giuseppe , Torrealba Jose , Rohlffs Fiona , Heidemann Franziska , Wessels Bart , Kölbel Tilo
Published: January 2022

Purpose:

The purpose of this study was to describe the use of a wire and catheters embedded with optical fiber (Fiber Optic RealShape [FORS]) to catheterize tortuous target vessels avoiding radiation.

Technique:

A virtual biplane vies was simulated coupling traditional x-ray system, preoperative CT scan, and FORS system to treat an isolated hypogastric aneurysm. Despite the complex anatomy, catheterization of all target vessels was possible in 12 minutes with 19 seconds of fluoroscopy time (Radiation Exposure 3.8 mGy×cm2). A minimal invasive endovascular exclusion of the aneurysm was achieved through selective coil-embolization of the iliolumbar artery and implantation of balloon expandable covered stents, thus preserving the perfusion of the superior gluteal artery.

Conclusion:

FORS guidance allowed catheterization of a target vessel with challenging anatomy with a low radiation exposure.
How do Hispanics/Latinos Perceive and Value the Return of Research Results?
Authors: Canedo Juan R. , Villalta-Gil Victoria , Grijalva Carlos G. , Schlundt David , Jerome Rebecca N. , Wilkins Consuelo H.
Published: January 2022

Introduction: Interest in the return of research results has been increasing; however, little is known about how Hispanics/Latinos perceive and value receiving results. This study examined differences among Hispanics/Latinos by education and income in the experience and expectations about the return of research results, perceived value of specific types of information, and the least and most valuable specific information. Method: Retrospective observational design using a cross-sectional national survey sample of Hispanics/Latinos (n = 327). Results: Higher educational attainment was positively associated with the expectation to receive research results, likelihood to participate in research if given study findings, and likelihood to trust researchers if given results. Higher income was positively associated with the perceived value of getting results. Respondents with higher education specifically perceived greater value in information about how lifestyle and genetics affect their risk of disease, how genetics affect how they respond to medications, their ancestry, available clinical trials near them, and how to connect with other study participants. Respondents with higher income perceived greater value in information about how genetics affect their risk of disease and how they respond to medications. Conclusion: The findings offer important insights for planning research initiatives and for developing culturally targeted educational materials for Hispanics/Latinos.
Hospital Frailty Risk Score and Healthcare Resource Utilization After Surgery for Primary Spinal Intradural/Cord Tumors
Authors: Elsamadicy Aladine A. , Koo Andrew B. , Reeves Benjamin C. , Pennington Zach , Sarkozy Margot , Hersh Andrew , Havlik John , Sherman Josiah J. Z. , Goodwin C. Rory , Kolb Luis , Laurans Maxwell , Larry Lo Sheng-Fu , Shin John H. , Sciubba Daniel M.
Published: January 2022

Objective

The Hospital Frailty Risk Score (HFRS) is a metric that measures frailty among patients in large national datasets using ICD-10 codes. While other metrics have been utilized to demonstrate the association between frailty and poor outcomes in spine oncology, none have examined the HFRS. The aim of this study was to investigate the impact of frailty using the HFRS on complications, length of stay, cost of admission, and discharge disposition in patients undergoing surgery for primary tumors of the spinal cord and meninges.

Methods

A retrospective cohort study was performed using the Nationwide Inpatient Sample database from 2016 to 2018. Adult patients undergoing surgery for primary tumors of the spinal cord and meninges were identified using ICD-10-CM codes. Patients were categorized into 2 cohorts based on HFRS score: Non-Frail (HFRS<5) and Frail (HFRS≥5). Patient characteristics, treatment, perioperative complications, LOS, discharge disposition, and cost of admission were assessed.

Results

Of the 5955 patients identified, 1260 (21.2%) were Frail. On average, the Frail cohort was nearly 8 years older ( P < .001) and experienced more postoperative complications ( P = .001). The Frail cohort experienced longer LOS ( P < .001), a higher rate of non-routine discharge ( P = .001), and a greater mean cost of admission ( P < .001). Frailty was found to be an independent predictor of extended LOS ( P < .001) and non-routine discharge ( P < .001).

Conclusion

Our study is the first to use the HFRS to assess the impact of frailty on patients with primary spinal tumors. We found that frailty was associated with prolonged LOS, non-routine discharge, and increased hospital costs.
The new equation of South Asia region: The rising role of China in Nepal's foreign policy
Authors: Pankaew Attasit , Kaewkhunok Suppawit
Published: January 2022

China's rising role in South Asia has contributed significantly to the changing geopolitics and geo-economics of the region. Nepal is one of the countries where relations with China have dramatically changed from 2015 till pre-pandemic. This study focuses on analyzing Nepal's foreign policy shifts towards neighboring China and India through a framework of neoclassical realism. It argues that Nepal's foreign policy against neighboring countries has changed since the India-Nepal conflict in 2015, where China has become a key option within Nepal's new foreign policy context. Changes in China's foreign policy and the victory of the Nepal Communist Party are among the key factors in enhancing relations between the two countries. However, it doesn't mean that Nepal took side with China and abandoned India. The article suggests that China's rise has a positive effect on Nepal as an option to balancing intra-regional power and opportunities for infrastructure development within the country.
COVID-19 Across the Landscape of Long-Term Care in Alameda County: Heterogeneity and Disparities
Authors: Hill Terry E. , Farrell David J.
Published: January 2022

Throughout the pandemic, public health and long-term care professionals in our urban California county have linked local and state COVID-19 data and performed observational exploratory analyses of the impacts among our diverse long-term care facilities (LTCFs). Case counts from LTCFs through March 2021 included 4309 (65%) in skilled nursing facilities (SNFs), 1667 (25%) in residential care facilities for the elderly (RCFEs), and 273 (4%) in continuing care retirement communities (CCRCs). These cases led to 582 COVID-19 resident deaths and 12 staff deaths based on death certificates. Data on decedents’ age, race, education, and country of birth reflected a hierarchy of wealth and socioeconomic status from CCRCs to RCFEs to SNFs. Mortality rates within SNFs were higher for non-Whites than Whites. Staff accounted for 42% of LTCF-associated COVID-19 cases, and over 75% of these staff were unlicensed. For all COVID-19 deaths in our jurisdiction, both LTCF and community, 82% of decedents were age 65 or over. Taking a comprehensive, population-based approach across our heterogenous LTCF landscape, we found socioeconomic disparities within COVID-19 cases and deaths of residents and staff. An improved data infrastructure linking public health and delivery systems would advance our understanding and potentiate life-saving interventions within this vulnerable ecosystem.
Retrospective analysis of adverse effects associated with pyrethrins-containing products
Authors: Osimitz Thomas G , Sioris Kelly , Gualtieri John , Filandrinos Dean , Seaverson Ryan , Carlson Angeline M , Droege Wiebke , Kingston Rick
Published: January 2022

The Pyrethrins Stewardship Program (PSP) was established to better understand adverse effects following exposure to pyrethrins-containing insecticide products. Running from April 2010 through December 2016, symptomatic dermal and inhalation exposures were entered into Phase I of the PSP and analyzed for exposure details and nature of the effects reported. Phase II consisted of an in-depth telephone interview using an enhanced questionnaire to investigate additional exposure details. Phase III scored the association between exposure and reported effects. Based on the data collected and analyzed, we conclude that: (1) Both in absolute number and relative to the wide distribution and use by consumers, adverse respiratory or dermal events after product exposure were rare; (2) Most outcomes for the reported events involving either dermal or respiratory effects were of minor severity and self-limiting; (3) None of the data collected and analyzed indicate that pyrethrins-containing products, including those formulated with synthetic pyrethroids and/or synergists, pose a significant risk of serious dermal or respiratory reactions even in cases where the exposed individual reported having allergies or asthma; (4) No additional label warnings or other mitigation techniques are warranted with pyrethrins-containing products formulated with or without synthetic pyrethroids and/or synergists.
Bone Union of Osseous Microvascular Free Tissue Transfer in Mandibular Reconstruction
Authors: Tamaki Akina , Sethuraman Shruthi , Shi Lucy , Zhao Songzhu , Carver Keith C. , Hatef Angel , Luttrull Michael , Seim Nolan B. , Kang Stephen Y. , Ozer Enver , Agrawal Amit , Old Matthew O.
Published: January 2022

Objectives

Osseous microvascular free tissue transfer (MFTT) is the gold standard for reconstruction for most segmental mandibulectomy defects. The most common osseous MFTT utilized in reconstruction is the fibular, scapular, and osteocutaneous radial forearm (OCRF) free flap. We evaluated postoperative bone union as well as clinical complications following MFTT and the impact of various patient and reconstructive characteristics, including type of osseous MFTT.

Study Design

Retrospective cohort study.

Setting

Tertiary care academic hospital.

Methods

This study examined patients who underwent osseous MFTT for mandibular defects from January 2017 to January 2019.

Results

An overall 144 osteotomies in 58 patients were evaluated. Of the 144 junctions, 28 (19.4%) showed radiographic nonunion. Patients who underwent preoperative (odds ratio [OR] = 0.30, P =. 027) and postoperative (OR = 0.28, P =. 003) radiation had a significantly lower bone union score. Time from surgery to postoperative imaging was associated with higher bone union scores (OR = 1.07, P =. 024). When bone union scores were compared among types of MFTT, fibular (OR = 5.62, P =. 008) and scapular (OR = 4.69, P =. 043) MFTT had significantly higher scores than OCRF MFTT. Twelve (20.7%) patients had postoperative complications. There was no statistically significant correlation between clinical complications and various variables, including type of osseous MFTT.

Conclusion

Pre‐ and postoperative radiation and time from surgery have an impact on bone union. Regarding the type of MFTT, fibular and scapular MFTT appeared to have higher bone union when compared with OCRF. There was no impact of bone union or type of osseous MFTT on clinical complications.
Psychiatry Disorders and Sociodemographic Profile of the Victims of Assault Attending the Teaching Hospital—Cross-Sectional Study
Authors: Bijjal Somashekhar , Iti Jannatbi , Ganiger Fakirappa B. , Mugali Jitendra , Mahadevappa Raju G.
Published: January 2022

Background:

According to World Health Organization, proportion of women experiencing either physical or sexual violence ranges between 15% and 17%. In India, one-third of women population in 15 to 49 age group experiences sexual assault at least once in their life, predisposing them to develop psychiatric disorders.

Aims and Objectives:

To assess prevalence of psychiatry disorders among victims of assault attending tertiary care center.

Methodology:

It is a retrospective, record-based study which was conducted among 216 victims of assault attending one-stop center. Study was started after obtaining Institutional Ethical Committee clearance and permissions from concerned authorities and confidentiality was maintained throughout the study. Data was analyzed by frequency, proportion, and chi-square tests using SPSS version 16.

Results:

Out of 216 victims, 50% were physically assaulted and 50% were sexually assaulted. Among 108 sexual assault cases, 81.5% victims were raped, 2.7% were sexually harassed, 1.9% was sexually abused, and 13.9% children were sexually abused. A total of 30.1% had adjustment disorder, 11.6% had dysthymia, 8.3% had mild depression, 5.6% had moderate depression, 0.5% had obsessive-compulsive disorder, 0.5% had psychosis, and 43.5% did not have any psychiatry disorder.

Conclusion:

Majority of the sexually assaulted victims belonged to age group 16 to 20 years and had adjustment disorder, whereas physically assaulted victims belonged to age group above 36 years and had dysthymia and depression. Special services like medical care, counseling, legal aid, and so on should be provided to victims free of charge. Awareness and sensitization programs should be done through active community participation for the welfare of children and women.
Cr-pyrope xenocrysts with oxide mineral inclusions from the Chompolo lamprophyres (Aldan shield): Insights into mantle processes beneath the southeastern Siberian craton
Authors: Rezvukhin Dmitriy I. , Nikolenko Evgeny I. , Sharygin Igor S. , Rezvukhina Olga V. , Chervyakovskaya Maria V. , Korsakov Andrey V.
Published: January 2022

Pyrope xenocrysts (N = 52) with associated inclusions of Ti- and/or Cr-rich oxide minerals from the Aldanskaya dyke and Ogonek diatreme (Chompolo field, southeastern Siberian craton) have been investigated. The majority of xenocrysts are of lherzolitic paragenesis and have concave-upwards (normal) rare earth element (REEN) patterns that increase in concentration from light REE to medium–heavy REE (Group 1). Four Ca-rich (5.7–7.4 wt.% CaO) pyropes are extremely low in Ti, Na and Y and have sinusoidal REEN spectra, thus exhibiting distinct geochemical signatures (Group 2). A peculiar xenocryst, s165, is the only sample to show harzburgitic derivation, whilst demonstrating a normal-to-weakly sinusoidal REEN pattern and the highest Zr (93 ppm) and Sc (471 ppm). Chromite–magnesiochromite, rutile, Mg-ilmenite and crichtonite-group minerals comprise a suite of oxide mineral inclusions in the pyrope xenocrysts. These minerals are characteristically enriched in Cr with 0.6–7.2 wt.% Cr2O3 in rutile, 0.7–3.6 wt.% in Mg-ilmenite and 7.1–18.0 wt.% in the crichtonite-group minerals. Complex titanates of the crichtonite group enriched in large ion lithophile elements (LILE) are high in Al2O3 (0.9–2.2 wt.%), ZrO2 (1.5–5.4 wt.%) and display a trend of compositions from the Ca–Sr-specific varieties to the Ba-dominant species (e.g. lindsleyite). In the pyrope xenocrysts the oxides coexist with silicates (clino- and orthopyroxene and olivine), hydrous silicates (talc, phlogopite and amphibole), carbonate (magnesite), sulfides (pentlandite, chalcopyrite, breakdown products of monosulfide and bornite solid solutions), apatite and graphite. P–T estimates imply the inclusion-bearing pyrope xenocrysts have been derived from low-temperature peridotite assemblages that resided at temperatures of ~600–800°C and a pressure range of ~25–35 kbar in the graphite stability field. Pyrope genesis is linked to the metasomatic enrichment of peridotite protoliths by Ca–Zr–LILE-bearing percolating fluid–melt phases containing significant volatile components. These metasomatic agents are probably volatile-rich melts or supercritical C–O–H–S fluids that were released from a Palaeo-subduction slab.
Congenital anemia reveals distinct targeting mechanisms for master transcription factor GATA1
Authors: Ludwig Leif S. , Lareau Caleb A. , Bao Erik L. , Liu Nan , Utsugisawa Taiju , Tseng Alex M. , Myers Samuel A. , Verboon Jeffrey M. , Ulirsch Jacob C. , Luo Wendy , Muus Christoph , Fiorini Claudia , Olive Meagan E. , Vockley Christopher M. , Munschauer Mathias , Hunter Abigail , Ogura Hiromi , Yamamoto Toshiyuki , Inada Hiroko , Nakagawa Shinichiro , Ohzono Shuichi , Subramanian Vidya , Chiarle Roberto , Glader Bertil , Carr Steven A. , Aryee Martin J. , Kundaje Anshul , Orkin Stuart H. , Regev Aviv , McCavit Timothy L. , Kanno Hitoshi , Sankaran Vijay G.
Published: January 2022

Master regulators, such as the hematopoietic transcription factor (TF) GATA1, play an essential role in orchestrating lineage commitment and differentiation. However, the precise mechanisms by which such TFs regulate transcription through interactions with specific cis-regulatory elements remain incompletely understood. Here, we describe a form of congenital hemolytic anemia caused by missense mutations in an intrinsically disordered region of GATA1, with a poorly understood role in transcriptional regulation. Through integrative functional approaches, we demonstrate that these mutations perturb GATA1 transcriptional activity by partially impairing nuclear localization and selectively altering precise chromatin occupancy by GATA1. These alterations in chromatin occupancy and concordant chromatin accessibility changes alter faithful gene expression, with failure to both effectively silence and activate select genes necessary for effective terminal red cell production. We demonstrate how disease-causing mutations can reveal regulatory mechanisms that enable the faithful genomic targeting of master TFs during cellular differentiation.
Sirolimus plus prednisolone vs sirolimus monotherapy for kaposiform hemangioendothelioma: a randomized clinical trial
Authors: Ji Yi , Chen Siyuan , Zhou Jiangyuan , Yang Kaiying , Zhang Xuepeng , Xiang Bo , Qiu Tong , Gong Xue , Zhang Zixin , Lan Yuru , Hu Fan , Kong Feiteng , Qiu Qingxia , Zhang Yongbo
Published: January 2022

The Kasabach-Merritt phenomenon (KMP) in kaposiform hemangioendothelioma (KHE) is characterized by life-threatening thrombocytopenia and consumptive coagulopathy. This study compared the efficacy and safety of sirolimus plus prednisolone vs sirolimus monotherapy as treatment strategies for KHE with KMP in the largest cohort to date. Participants were randomized to receive either sirolimus in combination with a short course of prednisolone or sirolimus monotherapy for at least 12 months. The primary outcome was defined as achievement of a durable platelet response (platelet count >100 × 109/L) at week 4. Participants completed efficacy assessments 2 years after the initial treatment. At week 4, a durable platelet response was achieved by 35 of 37 patients given sirolimus and prednisolone compared with 24 of 36 patients given sirolimus monotherapy (difference 27.9%; 95% confidence interval, 10.0-44.7). Compared with the sirolimus monotherapy group, the combination treatment group showed improvements in terms of measures of durable platelet responses at all points during the initial 3-week treatment period, median platelet counts during weeks 1 to 4, increased numbers of patients achieving fibrinogen stabilization at week 4, and objective lesion responses at month 12. Patients receiving combination therapy had fewer blood transfusions and a lower total incidence of disease sequelae than patients receiving sirolimus alone. The frequencies of total adverse events and grade 3-4 adverse events during treatment were similar in both groups. The responses seen in patients with KHE with KMP were profound and encouraging, suggesting that sirolimus plus prednisolone should be considered a valid treatment of KHE with KMP. This trial was registered at www.clinicaltrials.gov as #NCT03188068.
Regenerating islet-derived protein 3-α is a prognostic biomarker for gastrointestinal chronic graft-versus-host disease
Authors: DePriest Brittany Paige , Li Hong , Bidgoli Alan , Onstad Lynn , Couriel Daniel , Lee Stephanie J. , Paczesny Sophie
Published: January 2022

Prognostic biomarkers used to identify likelihood of disease progression have not been identified for chronic graft-versus-host disease (cGVHD), the leading cause of late nonrelapse mortality (NRM) in survivors of allogeneic hematopoietic cell transplantation. Gastrointestinal cGVHD (GI-cGVHD) has been particularly challenging to classify. Here, we analyzed 3 proteomics markers (Regenerating islet-derived protein 3-α [Reg3α], C-X-C motif ligand 9 [CXCL9], and Stimulation-2 [ST2]) in 2 independent cohorts of patients with cGVHD totaling 289 patients. Plasma concentrations of Reg3α were significantly increased in patients with GI-cGVHD (P = .0012) compared with those without (P = .01), but plasma concentrations of CXCL9 and ST2 were not. Patients with high Reg3α (≥72 ng/mL) vs low Reg3α had higher NRM (23% vs 11%; P = .015). Because Reg3α has been identified as a lower GI tract marker in acute GVHD, we correlated Reg3α with lower acute-like GI-cGVHD vs classical fibrotic-like esophageal manifestations and found that Reg3α did not differ between the subtypes. No difference was observed between upper GI tract and lower GI tract subtypes. Patients with extremely high Reg3α (≥180 ng/mL) had higher GI scores but not higher scores for the lower GI tract. In a multivariable Cox regression model, patients with high Reg3α were 1.9 times more likely to die without relapse. Our findings demonstrate the utility of Reg3α as a prognostic marker for GI-cGVHD. These data warrant prospective biomarker validation studies.
Indirect comparison of tisagenlecleucel and historical treatments for relapsed/refractory diffuse large B-cell lymphoma
Authors: Maziarz Richard T. , Zhang Jie , Yang Hongbo , Chai Xinglei , Yuan Chengbo , Schwarz Elisabeth , Jakovac Mihael , Martinez-Prieto Marcela , Agarwal Abhijit , Degtyarev Evgeny , Tam Constantine , Salles Gilles
Published: January 2022

No head-to-head trials have compared the efficacy of tisagenlecleucel vs historical treatments for adults with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). This study indirectly compared the overall survival (OS) and overall response rate (ORR) associated with tisagenlecleucel, using data from the JULIET study (Study of Efficacy and Safety of CTL019 in Adult DLBCL Patients; #NCT02445248), vs historical treatments assessed in the CORAL (Collaborative Trial in Relapsed Aggressive Lymphoma) study follow-up population. To assess treatment effects in the treated (full analysis set [FAS]) and enrolled (intention-to-treat [ITT]) study populations, the JULIET FAS vs the CORAL follow-up FAS and JULIET ITT vs CORAL follow-up ITT populations were separately compared. Propensity score weighting using standardized mortality ratio weight (SMRW) and fine stratification weight (FSW) was used to compare OS and ORR, adjusting for baseline confounders. The results indicated that tisagenlecleucel was associated with a lower hazard of death among the FAS (adjusted hazard ratio [95% confidence interval], both FSW and SMRW, 0.44 [0.32, 0.59]) and ITT populations (FSW, 0.60 [0.44, 0.77]; SMRW, 0.57 [0.44, 0.73]; all, P < .001). Median OS was 12.48 months (JULIET) vs 4.34 to 4.40 months (CORAL) for the FAS, and 8.25 (JULIET) months vs 4.04 to 4.86 (CORAL) months for the ITT populations. Tisagenlecleucel was associated with a significantly higher ORR compared with historical treatments among the FAS (adjusted response rate difference [95% confidence interval], both FSW and SMRW, 36% [22%, 0.48%]; P < .001) and among the ITT populations after SMRW adjustment (11% [0%, 22%]; P = .043). This analysis supports that improved response and OS are achieved in patients with r/r DLBCL treated with tisagenlecleucel compared with those treated with alternative historical treatments.
Fiducial markers for stereotactic lung radiation therapy: review of the transthoracic, endovascular and endobronchial approaches
Authors: Casutt Alessio , Kinj Rémy , Ozsahin Esat-Mahmut , von Garnier Christophe , Lovis Alban
Published: January 2022

Stereotactic body radiation therapy is an alternative to surgery for early-stage, inoperable peripheral non-small cell lung cancer. As opposed to linear accelerator (linac)-based (e.g.gating) and free-breathing techniques, CyberKnife® with Synchrony® technology allows accurate radiation delivery by means of a real-time respiratory motion tracking system using, in most cases, metal fiducial markers (FMs) placed in the vicinity of the target. The aims of this review are as follows. First, to describe the safety and efficacy of the transthoracic, endovascular and endobronchial FM insertion techniques for peripheral pulmonary lesions (PPLs). Second, to analyse performance in terms of the migration and tracking rates of different FM types. Recent developments in FM tracking for central lesions will also be reviewed. In conclusion, for PPLs, the endobronchial approach provides a low rate of pneumothorax, offers the possibility of concurrent diagnostic sampling for both the PPL and the lymph nodes, and, finally, reduces the intervention time compared to other techniques. In this context, coil-tailed and coil-spring FMs have shown the lowest migration rate with a consequently high tracking rate.
Abnormal lipid droplets accumulation induced cognitive deficits in obstructive sleep apnea syndrome mice via JNK/SREBP/ACC pathway but not through PDP1/PDC pathway
Authors: Li Dongze , Xu Na , Hou Yanyan , Ren Wenjing , Zhang Na , Wang Xi , Sun Yeying , Lu Wenxue , Qu Guiwu , Yu Yan , Lv Changjun , Han Fang
Published: January 2022

The mechanisms of chronic intermittent hypoxia (CIH)-induced cognitive deficits remain unclear. Here, our study found that about 3 months CIH treatment induced lipid droplets (LDs) accumulation in hippocampal nerve and glia cells of C57BL/6 mice, and caused severe neuro damage including neuron lesions, neuroblast (NB) apoptosis and abnormal glial activation. Studies have shown that the neuronal metabolism disorders might contribute to the CIH induced-hippocampal impairment. Mechanistically, the results showed that pyruvate dehydrogenase complex E1ɑ subunit (PDHA1) and the pyruvate dehydrogenase complex (PDC) activator pyruvate dehydrogenase phosphatase 1 (PDP1) did not noticeable change after intermittent hypoxia. Consistent with those results, the level of Acetyl-CoA in hippocampus did not significantly change after CIH exposure. Interestingly, we found that CIH produced large quantities of ROS, which activated the JNK/SREBP/ACC pathway in nerve and glia cells. ACC catalyzed the carboxylation of Acetyl-CoA to malonyl-CoA and then more lipid acids were synthesized, which finally caused aberrant LDs accumulation. Therefore, the JNK/SREBP/ACC pathway played a crucial role in the cognitive deficits caused by LDs accumulation after CIH exposure. Additionally, LDs were peroxidized by the high level of ROS under CIH conditions. Together, lipid metabolic disorders contributed to nerve and glia cells damage, which ultimately caused behavioral dysfunction. An active component ofSalvia miltiorrhiza, SMND-309, dramatically alleviated these injuries and improved cognitive deficits of CIH mice.
Degradome comparison between wild and cultivated rice identifies differential targeting by miRNAs
Authors: Swetha Chenna , Narjala Anushree , Pandit Awadhesh , Tirumalai Varsha , Shivaprasad P. V.
Published: January 2022

Background

Small non-coding (s)RNAs are involved in the negative regulation of gene expression, playing critical roles in genome integrity, development and metabolic pathways. Targeting of RNAs by ribonucleoprotein complexes of sRNAs bound to Argonaute (AGO) proteins results in cleaved RNAs having precise and predictable 5` ends. While tools to study sliced bits of RNAs to confirm the efficiency of sRNA-mediated regulation are available, they are sub-optimal. In this study, we provide an improvised version of a tool with better efficiency to accurately validate sRNA targets.

Results

Here, we improvised the CleaveLand tool to identify additional micro (mi)RNA targets that belong to the same family and also other targets within a specified free energy cut-off. These additional targets were otherwise excluded during the default run. We employed these tools to understand the sRNA targeting efficiency in wild and cultivated rice, sequenced degradome from two rice lines, O. nivara and O. sativa indica Pusa Basmati-1 and analyzed variations in sRNA targeting. Our results indicate the existence of multiple miRNA-mediated targeting differences between domesticated and wild species. For example, Os5NG4 was targeted only in wild rice that might be responsible for the poor secondary wall formation when compared to cultivated rice. We also identified differential mRNA targets of secondary sRNAs that were generated after miRNA-mediated cleavage of primary targets.

Conclusions

We identified many differentially targeted mRNAs between wild and domesticated rice lines. In addition to providing a step-wise guide to generate and analyze degradome datasets, we showed how domestication altered sRNA-mediated cascade silencing during the evolution of indica rice.
Genome-wide high-throughput signal peptide screening via plasmid pUC256E improves protease secretion in Lactiplantibacillus plantarum and Pediococcus acidilactici
Authors: Chen Binbin , Loo Bryan Zong Lin , Cheng Ying Ying , Song Peng , Fan Huan , Latypov Oleg , Kittelmann Sandra
Published: January 2022

Background

Proteases catalyze the hydrolysis of peptide bonds of proteins, thereby improving dietary protein digestibility, nutrient availability, as well as flavor and texture of fermented food and feed products. The lactobacilli Lactiplantibacillus plantarum (formerly Lactobacillus plantarum) and Pediococcus acidilactici are widely used in food and feed fermentations due to their broad metabolic capabilities and safe use. However, extracellular protease activity in these two species is low. Here, we optimized protease expression and secretion in L. plantarum and P. acidilactici via a genetic engineering strategy.

Results

To this end, we first developed a versatile and stable plasmid, pUC256E, which can propagate in both L. plantarum and P. acidilactici. We then confirmed expression and secretion of protease PepG1 as a functional enzyme in both strains with the aid of the previously described L. plantarum-derived signal peptide LP_0373. To further increase secretion of PepG1, we carried out a genome-wide experimental screening of signal peptide functionality. A total of 155 predicted signal peptides originating from L. plantarum and 110 predicted signal peptides from P. acidilactici were expressed and screened for extracellular proteolytic activity in the two different strains, respectively. We identified 12 L. plantarum signal peptides and eight P. acidilactici signal peptides that resulted in improved yield of secreted PepG1. No significant correlation was found between signal peptide sequence properties and its performance with PepG1.

Conclusion

The vector developed here provides a powerful tool for rapid experimental screening of signal peptides in both L. plantarum and P. acidilactici. Moreover, the set of novel signal peptides identified was widely distributed across strains of the same species and even across some closely related species. This indicates their potential applicability also for the secretion of other proteins of interest in other L. plantarum or P. acidilactici host strains. Our findings demonstrate that screening a library of homologous signal peptides is an attractive strategy to identify the optimal signal peptide for the target protein, resulting in improved protein export.