bluuebunny/crossref_metadata_2025 huggingface dataset:
Superiority of fecal carcinoembryonic antigen as diagnosis marker for adenomatous polyposis coli and asymptomatic colorectal cancer
Authors: Li Linfang , Gu Wenshen , Wu Xingping , Ao Yufeng , Song Yiling , Li Xiaohui , Zeng Qiuyao
Published: December 2021

Background:

Non-invasive diagnostic tools of adenomatous polyposis coli (APC) and asymptomatic colorectal cancer (CRC) are urgently needed. Although fecal carcinoembryonic antigen (FCEA) has been documented in some studies, the diagnostic potential for the detection of APC and asymptomatic CRC has not been described yet.

Methods:

This is a retrospective study. The pre-diagnostic serum carcinoembryonic antigen (SCEA) and fecal occult blood test (FOBT) levels were retrospectively analyzed in 212 patients with intestinal diseases group (IDG) and 224 controls. The levels of FCEA across all the studied groups were measured using electronic chemiluminescence immunoassay (ECLIA), and their sensitivity and specificity were used to evaluate their diagnostic potential. The individual diagnostic accuracy of the three indices, as well as their combined diagnostic potential, was compared using the receiver operating characteristic (ROC) curve and chi-square test.

Results:

The FCEA had low sensitivity (50%) and high specificity (93.91%) for the diagnosis of IDG, with the area under the curve (AUC) value of 0.781. The AUC of FCEA was higher than that of SCEA for the diagnosis of APC and CRC in the APC, asymptomatic CRC, and APC + CRC-stage I patients. The AUCs of FCEA were 0.708 and 0.691 for the ‘double-negative patients’ and ‘triple-negative patients’, respectively. In addition, FCEA could diagnose 45.5% of the ‘double-negative’ patients, 43.3% of the asymptomatic patients, and 42.9% of the ‘triple-negative’ patients. The combination of FCEA and FOBT improved the diagnostic value (AUC = 0.916).

Conclusion:

FCEA has been demonstrated to be a favorable diagnostic marker in intestinal diseases, especially in the APC, asymptomatic CRC, and ‘double-negative’ or ‘triple-negative’ CRC patients.
Gastro-oesophageal reflux disease increases healthcare use and medical costs in patients with bronchiectasis: a Korean nationwide population-based study
Authors: Yoon Jai Hoon , Kim Sang Hyuk , Ryu Jiin , Chung Sung Jun , Kim Youlim , Yoon Chang Ki , Ra Seung Won , Oh Yeon Mok , Choi Hayoung , Lee Hyun
Published: December 2021

Background:

Gastro-oesophageal reflux disease (GORD) is not only a common aetiology but also accompanying comorbidity of non-cystic fibrosis bronchiectasis (bronchiectasis). However, the association between GORD and the disease burden of bronchiectasis has not been well evaluated. Our study aimed to evaluate whether GORD is associated with increased healthcare use and medical costs in patients with bronchiectasis.

Methods:

We analyzed the data from 44,119 patients with bronchiectasis using a large representative Korean population-based claim database between 2009 and 2017. We compared the healthcare use [outpatient department (OPD) visits and emergency room (ER) visits/hospitalizations] and medical costs in patients with bronchiectasis according to the presence or absence of GORD.

Results:

The prevalence of GORD in patients with bronchiectasis tended to increase during the study period, especially in the 50s and older population. GORD was associated with increased use of all investigated healthcare resources in patients with bronchiectasis. Healthcare use including OPD visits (mean 47.6/person/year versus 30.0/person/year), ER visits/hospitalizations (mean 1.7/person/year versus 1.1/person/year), and medical costs (mean 3564.5 Euro/person/year versus 2198.7 Euro/person/year) were significantly higher in bronchiectasis patients with GORD than in those without GORD ( p < 0.001 for all). In multivariable analysis, bronchiectasis patients with GORD showed 1.44-fold (95% confidence interval = 1.37–1.50) and 1.26-fold (95% confidence interval = 1.19–1.33) increased all-cause and respiratory-related ER visits/hospitalizations relative to those without GORD, respectively. After adjusting for potential confounders, the estimated total medical costs (mean 4337.3 versus 3397.4 Euro/person/year) and respiratory disease-related medical costs (mean 920.7 versus 720.2 Euro/person/year) were significantly higher in bronchiectasis patients with GORD than in those without GORD ( p < 0.001 for both).

Conclusion:

In patients with bronchiectasis, GORD was associated with increased healthcare use and medical costs. Strategies to reduce the disease burden associated with GORD are needed in patients with bronchiectasis.
Helicobacter pylori diagnosis and therapy in the era of antimicrobial stewardship
Authors: Shiotani Akiko , Roy Priya , Lu Hong , Graham David Y.
Published: December 2021

The diagnosis and therapy of Helicobacter pylori infection have undergone major changes based on the use the principles of antimicrobial stewardship and increased availability of susceptibility profiling. H. pylori gastritis now recognized as an infectious disease, as such there is no placebo response allowing outcome to be assessed in relation to the theoretically obtainable cure rate of 100%. The recent recognition of H. pylori as an infectious disease has changed the focus to therapies optimized to reliably achieve high cure rates. Increasing antimicrobial resistance has also led to restriction of clarithromycin, levofloxacin, or metronidazole to susceptibility-based therapies. Covid-19 resulted in the almost universal availability of polymerase chain reaction testing in hospitals which can be repurposed to utilize readily available kits to provide rapid and inexpensive detection of clarithromycin resistance. In the United States, major diagnostic laboratories now offer H. pylori culture and susceptibility testing and American Molecular Laboratories offers next-generation sequencing susceptibility profiling of gastric biopsies or stools for the six commonly used antibiotics without need for endoscopy. Current treatment recommendations include (a) only use therapies that are reliably highly effective locally, (b) always perform a test-of-cure, and (c) use that data to confirm local effectiveness and share the results to inform the community regarding which therapies are effective and which are not. Empiric therapy should be restricted to those proven highly effective locally. The most common choices are 14-day bismuth quadruple therapy and rifabutin triple therapy. Prior guidelines and treatment recommendations should only be used if proven locally highly effective.
Infrared Thermography for the Evaluation of Inflammatory and Degenerative Joint Diseases: A Systematic Review
Authors: Schiavon Guglielmo , Capone Gianluigi , Frize Monique , Zaffagnini Stefano , Candrian Christian , Filardo Giuseppe
Published: December 2021

Objective

Inflammation plays a central role in the pathophysiology of rheumatic diseases as well as in osteoarthritis. Temperature, which can be quantified using infrared thermography, provides information about the inflammatory component of joint diseases. This systematic review aims at assessing infrared thermography potential and limitations in these pathologies.

Design

A systematic review was performed on 3 major databases: PubMed, Cochrane library, and Web of Science, on clinical reports of any level of evidence in English language, published from 1990 to May 2021, with infrared thermography used for diagnosis of osteoarthritis and rheumatic diseases, monitoring disease progression, or response to treatment. Relevant data were extracted, collected in a database, and analyzed for the purpose of this systematic review.

Results

Of 718 screened articles 32 were found to be eligible for inclusion, for a total of 2094 patients. Nine studies reported the application to osteoarthritis, 21 to rheumatic diseases, 2 on both. The publication trend showed an increasing interest in the last decade. Seven studies investigated the correlation of temperature changes with osteoarthritis, 16 with rheumatic diseases, and 2 with both, whereas 2 focused on the pre-post evaluation to investigate treatment results in patients with osteoarthritis and 5 in patients with rheumatic diseases. A correlation was shown between thermal findings and disease presence and stage, as well as the clinical assessment of disease activity and response to treatment, supporting infrared thermography role in the study and management of rheumatic diseases and osteoarthritis.

Conclusions

The systematic literature review showed an increasing interest in this technology, with several applications in different joints affected by inflammatory and degenerative pathologies. Infrared thermography proved to be a simple, accurate, noninvasive, and radiation-free method, which could be used in addition to the currently available tools for screening, diagnosis, monitoring of disease progression, and response to medical treatment.
Body mass index and vitamin D as risk factors for the development of uterine leiomyomas in Mexican women
Authors: Huseman-Plascencia Luz A , Villa-Villagrana Francisco , Ballesteros-Manzo Alberto , Baptista Rosas Raúl C. , Mercado-Sesma Arieh R , Arámbula-Chavolla Mar I
Published: December 2021

Objective:

The objective of the present study was to determine if body mass index and vitamin D levels are risk factors for the development of uterine leiomyomas in Mexican women.

Methods:

A cross-sectional study was designed. Inclusion criteria were women between 20 and 55 years with a suspect of uterine leiomyomas. Transvaginal ultrasonography was made to confirm the diagnosis and clinical variables were collected. Vitamin D levels were measured in serum by chemiluminescence immunoassay. Binary linear regression analysis was conducted to assess the predictors of uterine leiomyomas.

Results:

A total of 106 patients were evaluated, the mean age was 41.4 ± 8.0 years. The serum levels of vitamin D were insufficient in 94 (88.7%) and 82 (77.3%) has overweight or obesity. However, only 50 (47.2%) of participants have a diagnostic of uterine leiomyomas. BMI not increased the probability of having insufficient levels of vitamin D or uterine leiomyomas. Only, age (> 45 years) and levels of vitamin D (<30 ng/mL) were predictors of uterine leiomyomas (OR 10.345, 95% CI 2.737–39.095; p = 0.001; and OR 2.26, 95% CI 1.011–5.073; p = 0.014), respectively.

Conclusions:

Insufficient levels of vitamin D are common in Mexican women. Age and hypovitaminosis D are possible risk factors in the development of uterine leiomyomas in Mexican women.
Outcomes of Surgical Treatment of Migraines: A Systematic Review & Meta-Analysis
Authors: Evans Adam G. , Hill Dorian S. , Grush Andrew E. , Downer Mauricio A. , Ibrahim Maryo M. , Assi Patrick E. , Joseph Jeremy T. , Kassis Salam H.
Published: December 2021

Background: Migraine surgery at 1 of 6 identified “trigger sites” of a target cranial sensory nerve has rapidly grown in popularity since 2000. This study summarizes the effect of migraine surgery on headache severity, headache frequency, and the migraine headache index score which is derived by multiplying migraine severity, frequency, and duration. Materials and Methods: This is a PRISMA-compliant systematic review of 5 databases searched from inception through May 2020 and is registered under the PROSPERO ID: CRD42020197085. Clinical trials treating headaches with surgery were included. Risk of bias was assessed in randomized controlled trials. Meta-analyses were performed on outcomes using a random effects model to determine the pooled mean change from baseline and when possible, to compare treatment to control. Results: 18 studies met criteria including 6 randomized controlled trials, 1 controlled clinical trial, and 11 uncontrolled clinical trials treated 1143 patients with pathologies including migraine, occipital migraine, frontal migraine, occipital nerve triggered headache, frontal headache, occipital neuralgia, and cervicogenic headache. Migraine surgery reduced headache frequency at 1 year postoperative by 13.0 days per month as compared to baseline ( I2 = 0%), reduced headache severity at 8 weeks to 5 years postoperative by 4.16 points on a 0 to 10 scale as compared to baseline ( I2 = 53%), and reduced migraine headache index at 1 to 5 years postoperative by 83.1 points as compared to baseline ( I2 = 2%). These meta-analyses are limited by a small number of studies that could be analyzed, including studies with high risk of bias. Conclusion: Migraine surgery provided a clinically and statistically significant reduction in headache frequency, severity, and migraine headache index scores. Additional studies, including randomized controlled trials with low risk-of-bias should be performed to improve the precision of the outcome improvements.
La Solfeología en Materiales Educacionales. Un Análisis Documental
Authors: Borne Leonardo
Published: December 2021

Este estudio tiene por objetivo entender los conceptos y las concepciones que diferentes autores de materiales educacionales acuñaron sobre el solfeo. Fueron recopilados libros y otros materiales de solfeo en tres bibliotecas mexicanas, y con ellos se llevó a cabo un análisis documental que, además de los datos demográficos, tomó en cuenta cuatro categorías/pares conceptuales: habilidad o materia; atómico o integrado; sensación o razonamiento; de la notación al sonido o del sonido a la notación.

Los resultados apuntan a una predominancia de materiales de origen hispánico y anglosajón, en español o inglés, publicados entre 1950 y 2000. Además, pese a las diferentes vocaciones profesionales de las diferentes bibliotecas, los materiales hallados son muy similares entre sí. Con relación a los contenidos, en los materiales analizados el solfeo es concebido más frecuentemente como la habilidad de entonar atómicamente melodías a partir de la notación musical, basándose en el razonamiento. Por ende, es más común que el solfeo esté al servicio de la notación, no del sonido.

La importancia del estudio reside en el hecho de aportar datos para que las elecciones educacionales de los maestros respecto al solfeo sean más informadas y coherentes con sus contextos educativos, además de sumarse al cuerpo de la literatura existente sobre los análisis de materiales educacionales.
El análisis musical y los estudios sobre música popular urbana: de la doble negación a la educación en las discrepancias participatorias
Authors: García-Peinazo Diego
Published: December 2021

El análisis musical constituye una herramienta metodológica de primer orden para el estudio de las músicas populares urbanas en su conexión con procesos históricos, culturales, sociales, y políticos. La trayectoria académica de la relación entre ambos campos de estudio puede examinarse en términos de sus tensiones y disputas, pero también ha de valorarse en base al destacado potencial educativo de su encuentro. En este artículo se presenta un estado de la cuestión sobre las relaciones entre estos dos conjuntos disciplinares mostrando las posibles causas de una doble negación del análisis musical en los estudios sobre música popular exponiendo, tras ello, enfoques que apuestan por una renovación pedagógica basada en la implementación en las aulas tanto en modelos hermenéuticos de la canción popular como centrados en el análisis musical cooperativo. En la segunda parte del artículo se realiza un diagnóstico sobre la presencia de los enfoques analíticos de la música popular en la educación superior, a través del examen de planes de estudio de las siete universidades públicas españolas que ofertan el Grado en Historia y Ciencias de la Música. Por último, se plantean algunas reflexiones finales que abogan por la necesidad de un diálogo efectivo entre educación musical, análisis musical cooperativo y estudios sobre música popular.
Estrategias de aprendizaje sobre la expresividad musical en enseñanzas superiores e inteligencia emocional
Authors: Vallés Carolina Bonastre , Benítez Roberto Nuevo
Published: December 2021

La educación nos permite mejorar el desarrollo personal de cada individuo en aspectos tan relevantes como en el emocional. De hecho, la Inteligencia Emocional (IE) se ha vinculado con muchos resultados positivos en entornos educativos, pero apenas se ha estudiado en educación musical. El principal objetivo de este trabajo fue estudiar la relación entre la IE y las opiniones de estudiantes y profesores de música de enseñanzas superiores sobre estrategias para mejorar las capacidades expresivas: Modelado; uso de Metáforas; uso de las propias Emociones; e instrucciones Técnicas.

Los participantes fueron 117 estudiantes y 43 profesores que completaron sendos cuestionarios sobre IE y valoración de modelos de enseñanza-aprendizaje de la expresividad. Las estrategias Metáforas, Emociones y Técnica se asociaron positivamente con el nivel de IE aunque la diferencia de rol (docente-discente) parece poco relevante en esta asociación.

El vínculo entre estos aspectos sugiere que la mejora de las competencias emocionales y el aprendizaje expresivo están relacionados, de tal modo que favorecer el desarrollo de las destrezas emocionales de los estudiantes podría mejorar las habilidades expresivas en la interpretación musical y viceversa.
Efecto del entrenamiento musical en las funciones ejecutivas: un meta-análisis
Authors: Campos Mónica Hernández , Delgado Mauricio Molina , Smith-Castro Vanessa , Villagra Odir Rodríguez
Published: December 2021

En los últimos años ha surgido la interrogante de si es posible entrenar las funciones ejecutivas y si se considera que la música, por su alto nivel de complejidad, genera un efecto en estos procesos. Pese a que se ha encontrado una relación entre un entrenamiento musical y las funciones ejecutivas, estos resultados son contradictorios y no existe una estimación cuantitativa de la fuerza de esta posible asociación, ni tampoco estudios que integren los resultados de investigaciones similares para esclarecer la problemática planteada.

El objetivo del presente estudio fue estimar meta-analíticamente el efecto del entrenamiento musical sobre el procesamiento ejecutivo, así como identificar potenciales variables moderadoras. Se encontró un tamaño de efecto moderado ( d=0,51) el cual indica que las personas que recibieron un entrenamiento musical presentaron un mejor desempeño en las tareas de funciones ejecutivas e n comparación a los participantes que no estuvieron expuestos a un entrenamiento de esta naturaleza.
Maestros de música de Puerto Rico: Secuelas del huracán María
Authors: Candelas Marta Hernández , León Ricardo N. Lopez , Ortiz Yamil O.
Published: December 2021

En septiembre de 2017 llegaron a la isla de Puerto Rico dos de los huracanes más fuertes de la historia moderna. Más de 3.000 personas fallecieron y alrededor de 160.000 desalojaron la isla. Las pérdidas fueron mayores en todos los sectores. El propósito de este artículo se mueve en dos direcciones: primero, desde una perspectiva humanista y empática, observar la situación socioemocional de los maestros de música en Puerto Rico luego del paso de los huracanes Irma y María en septiembre de 2017; y, segundo, examinar las implicaciones laborales que estos fenómenos provocaron para el futuro de la enseñanza de la música de nivel primario y secundario y, de esta manera, considerar una agenda de gestiones y reflexiones prospectivas. Para el estudio se utilizó un cuestionario para identificar los daños sufridos a causa del huracán por los maestros de música de Puerto Rico. Este instrumento se diseñó tomando en cuenta artículos de la prensa del país, inquietudes de los investigadores y las ideas de cuestionarios para artistas sobrevivientes del huracán.
Trends and Treatment of Sub-Acute Sclerosing Panencephalitis: An Updated Review
Authors: Memon Shahzeb Ali , Afzal Syed Shabbir , Tukruna Alaa , Khan Asma Tasnim , Tebha Sameer Saleem , Zaidi Zain Ali
Published: December 2021

Measles infection, caused by the “Rubeola” virus is a highly contagious disease with outrageously fatal consequences. Initiating with a variety of symptoms including fever, cough, conjunctivitis, and runny nose, it can lead to more severe sequelae including sub-acute sclerosing pan-encephalitis which is a potentially fatal and serious complication of measles. The lackluster vaccination processes in underdeveloped areas of the world due to suboptimal immunization programs, scarce resources, and insufficient political constancy still leads to increased cases of measles and its complications. A variety of management programs including the use of several medications have been introduced according to the literature in order to counter this dreadful disease. In this review article, we focus on assessment of the previous literature and discussing the possible treatment modalities of this currently irremediable disease.
Transition from epoprostenol to selexipag in a patient with systemic sclerosis and pulmonary hypertension during the postoperative period of colon cancer surgery: A case report
Authors: Wada Takuma Tsuzuki , Yokota Kazuhiro , Iida Shinichiro , Kanno Yuki , Shinozuka Nozomi , Sato Kojiro , Asanuma Yu Funakubo , Yamamoto Keiji , Mimura Toshihide
Published: December 2021

Introduction:

Most pulmonary vasodilators are administered orally; however, in patients with pulmonary hypertension undergoing gastrointestinal surgery, a switch to parenteral drugs is needed. Parenteral pulmonary vasodilators carry a risk of infection and reduced quality of life owing to long-term central venous catheterization; therefore, it is preferable to switch them to oral vasodilators after surgery. Here, we present the case of a patient with systemic sclerosis complicated by pulmonary hypertension and colon cancer, for which treatment was successfully switched from epoprostenol to selexipag postoperatively.

Case Description:

A 59-year-old woman, who was diagnosed with mixed group I and III pulmonary hypertension and systemic sclerosis, was on oral triple pulmonary vasodilators for pulmonary hypertension and Raynaud’s phenomenon. She was diagnosed as having colon cancer 3 months before admission. Despite the severe pulmonary condition and treatment with oral triple pulmonary vasodilators, colon cancer resection surgery was performed with the management for pulmonary hypertension through multidisciplinary treatments in collaboration with cardiology specialists. Medications for patients with pulmonary hypertension undergoing gastrointestinal surgery need to be switched from oral vasodilators to epoprostenol perioperatively. On postoperative day 19, 0.4 mg/day of selexipag was administered with epoprostenol. Subsequently, the epoprostenol dosage was gradually decreased, and selexipag was increased. On postoperative day 30, the dose of selexipag was increased to 1.2 mg/day and epoprostenol was discontinued. The patient was discharged on postoperative day 40.

Conclusion:

In our case, transition from epoprostenol to selexipag contributed to a more useful management strategy for systemic sclerosis and pulmonary hypertension in the postoperative period.
A Retrospective Study on the Effectiveness of Ixekizumab After Treatment With Secukinumab for Patients With Active Psoriatic Arthritis
Authors: Darabian Saman , Badii Maziar , Dutz Jan P. , Chan Jonathan
Published: December 2021

Objectives: This study aims to evaluate clinical responses in patients with active psoriatic arthritis who, despite secukinumab 300 mg subcutaneous monthly, are switched to ixekizumab 80 mg subcutaneous every four weeks. Methods: We conducted a chart review of adult patients with psoriatic arthritis treated at one clinical center. We identified all patients with active inflammatory arthritis who were switched from secukinumab to ixekizumab. Baseline demographics such as disease duration, age, gender, number of previous DMARDs, and previous time on secukinumab were collected. We collected clinical outcome data such as tender and swollen joint count, enthesitis based on SPARCC score, dactylitis, psoriasis severity, CRP, and BASDAI if axial involvement was present. Results: Eight of 10 patients were included in the analysis. Most patients were female, average age 62 years old, and had been on secukinumab for an average of 79 weeks. Twelve weeks following switch to ixekizumab, 6/8 had improvement in tender joint count, 6/8 improved in swollen joint count, 2/2 had resolution of enthesitis, 4/4 had resolution of dactylitis, 5/6 had improvement in psoriasis severity, 1 patient had absolute improvement of 2.3 in BASDAI, and 7/8 had improvement in the CRP level. Conclusions: Patients with active psoriatic arthritis despite treatment with secukinumab may still have a clinical response following treatment with another anti-IL17 agent. Larger studies will be required to confirm this finding, and studies which emphasize dactylitis and enthesitis outcomes will be needed as most patients did not have activity in these domains.
Individual animal geographies for the more-than-human city: Storying synanthropy and cynanthropy with urban coyotes
Authors: Van Patter Lauren E
Published: December 2021

Recent efforts within geography to deconstruct anthropocentric readings of the urban and explore the city as ‘multispecies’ or ‘more-than-human’ face substantial methodological challenges. This paper contributes an empirical case study of human-coyote urban cohabitations in the Greater Toronto Area, Canada, using a ‘hybrid’ methodological approach to individual animal geographies. It builds on dialogues surrounding animals’ geographies that centre individual animal lifeworlds and experiences, exploring coyotes as subjects and actors who participate in the co-creation of shared urban worlds. A methodological approach based on collaboration and storying recounts the tales of two coyotes – Urban10 and Blondie – and their kin whose stories are gleaned by weaving together diverse social and ecological research tools, including: participant observation with Coyote Watch Canada, document review, semi-structured interviews, GPS collar data, field investigations, ethological observations, and trail cameras. The discussion details implications in terms of cynanthropy – ‘becoming-canid’ as methodology, delving into coyote lifeworlds using hybrid tools – as well as synanthropy – coyote synurbization and more-than-human urban belongings. Dwelling with Urban10 and Blondie in cynanthropic exploration makes visible opportunities for multispecies researchers to generate knowledge collaboratively with other-than-humans. Findings surrounding synanthropy highlight the practices involved in adapting to and participating, ecologically and socially, in life in the multispecies city. Overall, this paper advances efforts aimed at developing innovative and experimental hybrid methodologies for animal geographies, and theoretical discussions around re-storying the more-than-human city towards livable multispecies futures.
Making land grabbable: Stealthy dispossessions by conservation in Ngorongoro Conservation Area, Tanzania
Authors: Weldemichel Teklehaymanot G.
Published: December 2021

This paper seeks to answer the question: how does land become grabbable and local people relocatable? It focuses on the historical and current conditions of land tenure that enable land grabbing. While recognising the important contributions thus far made by the critical literature on land grabbing, this paper moves forward towards understanding specific processes that befall before land is grabbed and its original users relocated. Based on an empirical analysis of policy and practices of the Ngorongoro Conservation Area in Tanzania, the paper proposes that land grabbing, particularly in the context of conservation in rural Africa, is not an instantaneous phenomenon and does not happen in a vacuum. It is a result of long-term structural marginalisation of rural land users that produces scarcity and the deterioration of life conditions, which make people relocatable and land grabbing justifiable. Local people either relocate themselves because they could not make a living due to systematic disinvestments on basic social services or life is made unbearable through restrictions imposed on their production practices to make “voluntary” relocation possible. The paper highlights the need to focus on the stealthy dispossessions in addition to major events of grabbing as starting points of analysis. Insight from this study can be useful in analysing other cases of land grabbing where large swathes of ostensibly empty land are made available for investment.
Ineffective erythropoiesis and its treatment
Authors: Cazzola Mario
Published: December 2021

The erythroid marrow and circulating red blood cells (RBCs) are the key components of the human erythron. Abnormalities of the erythron that are responsible for anemia can be separated into 3 major categories: erythroid hypoproliferation, ineffective erythropoiesis, and peripheral hemolysis. Ineffective erythropoiesis is characterized by erythropoietin-driven expansion of early-stage erythroid precursors, associated with apoptosis of late-stage precursors. This mechanism is primarily responsible for anemia in inherited disorders like β-thalassemia, inherited sideroblastic anemias, and congenital dyserythropoietic anemias, as well as in acquired conditions like some subtypes of myelodysplastic syndrome (MDS). The inherited anemias that are due to ineffective erythropoiesis are also defined as iron-loading anemias because of the associated parenchymal iron loading caused by the release of erythroid factors that suppress hepcidin production. Novel treatments specifically targeting ineffective erythropoiesis are being developed. Iron restriction through enhancement of hepcidin activity or inhibition of ferroportin function has been shown to reduce ineffective erythropoiesis in murine models of β-thalassemia. Luspatercept is a transforming growth factor-β ligand trap that inhibits SMAD2/3 signaling. Based on preclinical and clinical studies, this compound is now approved for the treatment of anemia in adult patients with β-thalassemia who require regular RBC transfusions. Luspatercept is also approved for the treatment of transfusion-dependent anemia in patients with MDS with ring sideroblasts, most of whom carry a somatic SF3B1 mutation. While the long-term effectiveness and safety of luspatercept need to be evaluated in β-thalassemia and MDS, defining the molecular mechanisms of ineffective erythropoiesis in different disorders might allow the discovery of new effective compounds.
SIPA in 10 milliseconds: VWF tentacles agglomerate and capture platelets under high shear
Authors: Liu Zixiang Leonardo , Bresette Christopher , Aidun Cyrus K. , Ku David N.
Published: December 2021

Shear-induced platelet aggregation (SIPA) occurs under elevated shear rates (10 000 s−1) found in stenotic coronary and carotid arteries. The pathologically high shear environment can lead to occlusive thrombosis by SIPA from the interaction of nonactivated platelets and von Willebrand factor (VWF) via glycoprotein Ib–A1 binding. This process under high shear rates is difficult to visualize experimentally with concurrent molecular- and cellular-resolutions. To understand this fast bonding, we employ a validated multiscale in silico model incorporating measured molecular kinetics and a thrombosis-on-a-chip device to delineate the flow-mediated biophysics of VWF and platelets assembly into mural microthrombi. We show that SIPA begins with VWF elongation, followed by agglomeration of platelets in the flow by soluble VWF entanglement before mural capture of the agglomerate by immobilized VWF. The entire SIPA process occurs on the order of 10 milliseconds with the agglomerate traveling a lag distance of a few hundred microns before capture, matching in vitro results. Increasing soluble VWF concentration by ∼20 times in silico leads to a ∼2 to 3 times increase in SIPA rates, matching the increase in occlusion rates found in vitro. The morphology of mural aggregates is primarily controlled by VWF molecular weight (length), where normal-length VWF leads to cluster or elongated aggregates and ultra-long VWF leads to loose aggregates seen by others’ experiments. Finally, we present phase diagrams of SIPA, which provides biomechanistic rationales for a variety of thrombotic and hemostatic events in terms of platelet agglomeration and capture.
Health-related quality of life with idecabtagene vicleucel in relapsed and refractory multiple myeloma
Authors: Delforge Michel , Shah Nina , Miguel Jesús San F. , Braverman Julia , Dhanda Devender S. , Shi Ling , Guo Shien , Yu Peiwen , Liao Weiqin , Campbell Timothy B. , Munshi Nikhil C.
Published: December 2021

Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen–directed chimeric antigen receptor T cell therapy, showed deep, durable responses in patients with triple-class exposed, relapsed and refractory multiple myeloma (RRMM) in the phase 2 KarMMa (Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma) trial. We assessed health-related quality of life (HRQoL) among KarMMa patients. The European Organization for Research and Treatment of Cancer Quality of Life C30 Questionnaire and its supplementary 20-item multiple myeloma module, as well as the EuroQol 5-dimension 5-level instrument, were administered at screening, baseline (≤72 hours before or same day as lymphodepletion), day of ide-cel treatment, and after ide-cel treatment. Mean changes from baseline that exceeded the predetermined threshold of minimally important difference were deemed clinically meaningful. The proportions of patients experiencing clinically meaningful changes in HRQoL were assessed using within-patient change thresholds. Time to stable improvement (≥2 consecutive visits with clinically meaningful HRQoL improvements) was analyzed by using the Kaplan-Meier method. A total of 126 (98%) of 128 patients treated with ide-cel were included in the HRQoL analysis. Pretreatment baseline RRMM burden was high and meaningfully worse than that in the age- and sex-weighted general population. Statistically significant and clinically meaningful improvements from baseline were observed by month 1 for pain (−8.9) and disease symptoms (−10.2), and by month 2 for fatigue (−7.2), physical functioning (6.1), cognitive functioning (6.7), and global health status/QoL (8.0). Clinically meaningful improvements in fatigue, pain, and physical functioning were most prominent at months 9, 12, and 18, respectively, and were sustained through 15 to 18 months after ide-cel treatment. For triple-class exposed patients with RRMM with a poor prognosis and few treatment options, a single ide-cel infusion provides early, sustained, statistically significant, and clinically meaningful improvements in HRQoL. This study was registered at Clinicaltrials.gov as #NCT03361748.
Appearance of claudin-5+ leukocyte subtypes in the blood and CNS during progression of EAE
Authors: Krajewski Dylan , Paul Debayon , Ge Shujun , Jellison Evan , Pachter Joel S.
Published: December 2021

Background

Tight junctions (TJs) are membrane specializations characteristic of barrier-forming membranes, which function to seal the aqueous pathway between endothelial cells or epithelial cells and, thereby, obstruct intercellular solute and cellular movement. However, previous work from our laboratory found that claudin-5 (CLN-5), a TJ protein prominent at the blood–brain barrier (BBB), was also detected, ectopically, on leukocytes (CLN-5+) in the blood and central nervous system (CNS) of mice with experimental autoimmune encephalomyelitis (EAE), a neuroinflammatory, demyelinating disease that is a model for multiple sclerosis. CLN-5 was further shown to be transferred from endothelial cells to circulating leukocytes during disease, prompting consideration this action is coupled to leukocyte transendothelial migration (TEM) into the CNS by fostering transient interactions between corresponding leukocyte and endothelial junctional proteins at the BBB.

Methods

To begin clarifying the significance of CLN-5+leukocytes, flow cytometry was used to determine their appearance in the blood and CNS during EAE.

Results

Flow cytometric analysis revealed CLN-5+populations among CD4 and CD8 T cells, B cells, monocytes and neutrophils, and these appeared with varying kinetics and to different extents in both blood and CNS. CLN-5 levels on circulating T cells further correlated highly with activation state. And, the percentage of CLN-5+cells among each of the subtypes analyzed was considerably higher in CNS tissue than in blood, consistent with the interpretation that CLN-5+leukocytes gain preferred access to the CNS.

Conclusion

Several leukocyte subtypes variably acquire CLN-5 in blood before they enter the CNS, an event that may represent a novel mechanism to guide leukocytes to sites for paracellular diapedesis across the BBB.
Hypoxic in vitro culture reduces histone lactylation and impairs pre-implantation embryonic development in mice
Authors: Yang Wanting , Wang Peijun , Cao Pengbo , Wang Shuang , Yang Yuxiao , Su Huimin , Nashun Buhe
Published: December 2021

Background

Dynamic changes of histone posttranslational modifications are important contexts of epigenetic reprograming after fertilization in pre-implantation embryos. Recently, lactylation has been reported as a novel epigenetic modification that regulates various cellular processes, but its role during early embryogenesis has not been elucidated.

Results

We examined nuclear accumulation of H3K23la, H3K18la and pan histone lactylation in mouse oocytes and pre-implantation embryos by immunofluorescence with specific antibodies. All of the three modifications were abundant in GV stage oocytes, and both H3K23la and pan histone lactylation could be detected on the condensed chromosomes of the MII oocytes, while H3K18la were not detected. After fertilization, the nuclear staining of H3K23la, H3K18la and pan histone lactylation was faint in zygotes but homogeneously stained both of the parental pronuclei. The signal remained weak in the early cleavage stage embryos and increased remarkably in the blastocyst stage embryos. Comparison of the embryos cultured in four different conditions with varying concentrations of oxygen found that H3K23la, H3K18la and pan histone lactylation showed similar and comparable staining pattern in embryos cultured in atmospheric oxygen concentration (20% O2), gradient oxygen concentration (5% O2to 2% O2) and embryos obtained from in vivo, but the modifications were greatly reduced in embryos cultured in hypoxic condition (2% O2). In contrast, nuclear accumulation of H3K18ac or H3K23ac was not significantly affected under hypoxic condition. Moreover, the developmental rate of in vitro cultured embryo was significantly reduced by low oxygen concentration and small molecule inhibition of LDHA activity led to decreased lactate production, as well as reduced histone lactylation and compromised developmental rate.

Conclusions

We provided for the first time the dynamic landscape of H3K23la, H3K18la and pan histone lactylation in oocytes and pre-implantation embryos in mice. Our data suggested that histone lactylation is subjected to oxygen concentration in the culture environment and hypoxic in vitro culture reduces histone lactylation, which in turn compromises developmental potential of pre-implantation embryos in mice.
Melatonin-primed ADMSCs elicit an efficacious therapeutic response in improving high-fat diet induced non-alcoholic fatty liver disease in C57BL/6J mice
Authors: Vohra Aliasgar Hatimbhai , Upadhyay Kapil Kumar , Joshi Apeksha Suhas , Vyas Hitarthi Swetang , Thadani Jaymesh , Devkar Ranjitsinh Vijaysinh
Published: December 2021

Background

Stem cells are widely used for therapy including treatment of liver damage. Adipose-derived mesenchymal stem cells (ADMSCs) administered to treat fatty liver are known to improve liver function but their use is restricted due to a poor success rate. This study investigates efficacy of melatonin-primed ADMSCs (Mel. MSCs) in experimentally induced non-alcoholic fatty liver disease (NAFLD).

Results

MSCs treated with LPS showed prominent DCFDA fluorescence as compared to the untreated cells. Also, the JC-1 staining had accounted for higher intensity of green monomer and a weak fluorescence of red dimer indicating weaker mitochondrial membrane potential. But melatonin co-treatment could make necessary corrective changes as evidenced by reverse set of results. The overall cell survival was also found to be improved following melatonin treatment as evidenced by the MTT assay. Also, the antioxidant (Nrf2 and Ho-1) and anti-inflammatory genes (Il-4 and Il-10) showed a decrement in their mRNA levels following LPS treatment whereas the pro-inflammatory genes (Tnf-α, Il-6, Tlr-4, and Lbp) showed a reciprocal increment in the said group. Melatonin co-treatment accounted for an improved status of antioxidant and anti-inflammatory genes as evidenced by their mRNA levels. High-fat high-fructose diet (HFFD) fed C57BL/6J mice recorded higher serum AST and ALT levels and fatty manifestation in histology of liver along with lowered mRNA levels of antioxidant (Nrf2, Catalase, and Gss) genes and Hgf. These set of parameters showed a significant improvement in HFFD + Mel.MSC group.

Conclusion

A significant improvement in viability of MSCs was recorded due to lowered intracellular oxidative stress and improves mitochondrial membrane potential. Further, melatonin-primed MSCs accounted for a significant decrement in fatty manifestations in liver and an improved physiological status of NAFLD in HFFD fed C57BL/6J mice. Taken together, it is hypothesized that melatonin priming to MSCs prior to its use can significantly augment the success of stem cell therapy.
Cyp11a2 Is Essential for Oocyte Development and Spermatogonial Stem Cell Differentiation in Zebrafish
Authors: Wang Yaqing , Ye Ding , Zhang Fenghua , Zhang Ru , Zhu Junwen , Wang Houpeng , He Mudan , Sun Yonghua
Published: December 2021

Cytochrome P45011A1, encoded by Cyp11a1, converts cholesterol to pregnenolone (P5), the first and rate-limiting step in steroidogenesis. In zebrafish, cyp11a1 is maternally expressed and cyp11a2 is considered the ortholog of Cyp11a1 in mammals. A recent study has shown that depletion of cyp11a2 resulted in steroidogenic deficiencies and the mutants developed into males with feminized secondary sexual characteristics. Here, we independently generated cyp11a2 mutants in zebrafish and showed that the mutants can develop into males and females in the juvenile stage, but finally into infertile males with defective mating behavior in the adult stage. In the developing ovaries, the cyp11a2 mutation led to stage I oocyte apoptosis and final sex reversal, which could be partially rescued by treatment with P5 but not estradiol. In the developing testes, depletion of cyp11a2 resulted in dysfunction of Sertoli cells and lack of functional Leydig cells. Spermatogonial stem cells (SSCs) in the mutant testes underwent active self-renewal but no differentiation, resulting in a high abundance of SSCs in the testis, as revealed by immunofluorescence staining with Nanos2 antibody. The high abundance and differentiation competence of SSCs in the mutant testes were verified by a novel testicular cell transplantation method developed in this study, by transplanting mutant testicular cells into germline-depleted wild-type (WT) fish. The transplanted mutant SSCs efficiently differentiated into functional spermatids in WT hosts. Overall, our study demonstrates the functional importance of cyp11a2 in early oogenesis and differentiation of SSCs.
Transcription factor-like 5 is a potential DNA- and RNA-binding protein essential for maintaining male fertility in mice
Authors: Xu Weiya , Zhang Yiyun , Qin Dongdong , Gui Yiqian , Wang Shu , Du Guihua , Yang Fan , Li Lufan , Yuan Shuiqiao , Wang Mei , Wu Xin
Published: December 2021

Transcription factor-like 5 (TCFL5) is a testis-specific protein that contains the basic helix-loop-helix domain, but the in vivo functions of TCFL5 remain unknown. Herein, we generated CRISPR/Cas9-mediated knockout mice to dissect the function of TCFL5 in mouse testes. Surprisingly, we found that it was difficult to generate homozygous mice with the Tcfl5 deletion as the heterozygous males (Tcfl5+/−) were infertile. However, we did observe markedly abnormal phenotypes of spermatids and spermatozoa in the testes and epididymides of Tcfl5+/− mice. Mechanistically, we demonstrated that TCFL5 transcriptionally and post-transcriptionally regulated a set of genes participating in male germ cell development via TCFL5 ChIP-DNA and eCLIP-RNA high-throughput sequencing. We also identified a known RNA-binding protein, FXR1, as an interacting partner of TCFL5 that may coordinate the transition and localization of TCFL5 in the nucleus. Collectively, we herein report for the first time that Tcfl5 is haploinsufficient in vivo and acts as a dual-function protein that mediates DNA and RNA to regulate spermatogenesis.

This article has an associated First Person interview with the first author of the paper.
Energetic costs of ectoparasite infection in Atlantic salmon
Authors: Hvas Malthe , Bui Samantha
Published: December 2021

Parasites are widespread in nature, where they affect the energy budget of hosts, and depending on the imposed pathogenic severity, this may reduce host fitness. However, the energetic costs of parasite infections are rarely quantified. In this study, we measured metabolic rates in recently seawater adapted Atlantic salmon (Salmo salar) infected with the ectoparasitic copepod Lepeophtheirus salmonis and used an aerobic scope framework to assess the potential ecological impact of this parasite–host interaction. The early chalimus stages of L. salmonis did not affect either standard or maximum metabolic rates. However, the later mobile pre-adult stages caused an increase in both standard and maximum metabolic rate yielding a preserved aerobic scope. Notably, standard metabolic rates were elevated by 26%, presumably caused by increased osmoregulatory burdens and costs of mobilizing immune responses. The positive impact on maximum metabolic rates was unexpected and suggests that fish are able to transiently overcompensate energy production to endure the burden of parasites and thus allow for continuation of normal activities. However, infected fish are known to suffer reduced growth, and this suggests that a trade-off exists in acquisition and assimilation of resources despite an uncompromised aerobic scope. As such, when assessing impacts of environmental or biotic factors, we suggest that elevated routine costs may be a stronger predictor of reduced fitness than the available aerobic scope. Furthermore, studying the effects on parasitized fish in an ecophysiological context deserves more attention, especially considering interacting effects of other stressors in the Anthropocene.