bluuebunny/crossref_metadata_2025 huggingface dataset:
Cloning, expression, and one-step purification/immobilization of two carbohydrate-binding module-tagged alcohol dehydrogenases
Authors: Benito Mario , Román Ramón , Ortiz Garazi , Casablancas Antoni , Álvaro Gregorio , Caminal Gloria , González Gloria , Guillén Marina
Published: June 2022

Background

The feasibility of biochemical transformation processes is usually greatly dependent on biocatalysts cost. Therefore, immobilizing and reusing biocatalysts is an approach to be considered to bring biotransformations closer to industrial feasibility, since it does not only allow to reuse enzymes but can also improve their stability towards several reaction conditions. Carbohydrate-Binding Modules (CBM) are well-described domains involved in substrate binding which have been already used as purification tags.

Results

In this work, two different Carbohydrate-Binding Modules (CBM3 and CBM9) have been successfully fused to an alcohol dehydrogenase fromSaccharomyces cerevisiae, which has been produced in bench-scale reactor using an auxotrophic M15-derivedE. colistrain, following a fed-batch strategy with antibiotic-free medium. Around 40 mg·g− 1DCW of both fusion proteins were produced, with a specific activity of > 65 AU·mg− 1. Overexpressed proteins were bound to a low-cost and highly selective cellulosic support by one-step immobilization/purification process at > 98% yield, retaining about a 90% of initial activity. Finally, the same support was also used for protein purification, aiming to establish an alternative to metal affinity chromatography, by which CBM9 tag proved to be useful, with a recovery yield of > 97% and 5-fold increased purity grade.

Conclusion

CBM domains were proved to be suitable for one-step immobilization/purification process, retaining almost total activity offered. However, purification process was only successful with CBM9.
Prenatal diagnosis of Williams-Beuren syndrome by ultrasound and chromosomal microarray analysis
Authors: Huang Ruibin , Zhou Hang , Fu Fang , Li Ru , Lei Tingying , Li Yingsi , Cheng Ken , Wang You , Yang Xin , Li Lushan , Jing Xiangyi , Zhang Yongling , Li Fucheng , Li Dongzhi , Liao Can
Published: June 2022

Background

There are a few literature reports of prenatal ultrasound manifestations of Williams-Beuren syndrome. We aimed to explore the prenatal diagnosis of Williams-Beuren syndrome by ultrasound and chromosomal microarray analysis and describe the prenatal ultrasound performance of this syndrome.

Methods

In this retrospective study, we reported eight cases of Williams-Beuren syndrome diagnosed at our prenatal diagnostic center from 2016 to 2021. We systematically reviewed clinical data from these cases, including indications for invasive testing, sonographic findings, QF-PCR results, chromosomal microarray analysis results, and pregnancy outcomes.

Results

In this study, the common ultrasound features were ventricular septal defect (37.5%), intrauterine growth retardation (25%), and aortic coarctation (25%). Moreover, all patients were found to have a common deletion in the Williams-Beuren syndrome chromosome region at the 7q11.23 locus, which contained the elastin gene. Deletion sizes ranged from 1.42 to 2.07 Mb. Seven parents asked for termination of pregnancy, and one patient was lost to follow-up.

Conclusions

This study is the most extensive prenatal study using chromosomal microarray analysis technology for detailed molecular analysis of Williams-Beuren syndrome cases. We reported three cases combined with first-reported ultrasound manifestations. Case 1 was concomitant with multicystic dysplastic kidney and duodenal atresia combined with case 3. Notably, case 4 was combined with multiple cardiovascular malformations: Tetralogy of Fallot, right aortic arch, and supravalvar aortic stenosis. These manifestations expand the intrauterine ultrasound phenotype of Williams-Beuren syndrome in previous literature reports.
Emerging role of exosomes in cancer progression and tumor microenvironment remodeling
Authors: Paskeh Mahshid Deldar Abad , Entezari Maliheh , Mirzaei Sepideh , Zabolian Amirhossein , Saleki Hossein , Naghdi Mohamad Javad , Sabet Sina , Khoshbakht Mohammad Amin , Hashemi Mehrdad , Hushmandi Kiavash , Sethi Gautam , Zarrabi Ali , Kumar Alan Prem , Tan Shing Cheng , Papadakis Marios , Alexiou Athanasios , Islam Md Asiful , Mostafavi Ebrahim , Ashrafizadeh Milad
Published: June 2022

Cancer is one of the leading causes of death worldwide, and the factors responsible for its progression need to be elucidated. Exosomes are structures with an average size of 100 nm that can transport proteins, lipids, and nucleic acids. This review focuses on the role of exosomes in cancer progression and therapy. We discuss how exosomes are able to modulate components of the tumor microenvironment and influence proliferation and migration rates of cancer cells. We also highlight that, depending on their cargo, exosomes can suppress or promote tumor cell progression and can enhance or reduce cancer cell response to radio- and chemo-therapies. In addition, we describe how exosomes can trigger chronic inflammation and lead to immune evasion and tumor progression by focusing on their ability to transfer non-coding RNAs between cells and modulate other molecular signaling pathways such as PTEN and PI3K/Akt in cancer. Subsequently, we discuss the use of exosomes as carriers of anti-tumor agents and genetic tools to control cancer progression. We then discuss the role of tumor-derived exosomes in carcinogenesis. Finally, we devote a section to the study of exosomes as diagnostic and prognostic tools in clinical courses that is important for the treatment of cancer patients. This review provides a comprehensive understanding of the role of exosomes in cancer therapy, focusing on their therapeutic value in cancer progression and remodeling of the tumor microenvironment.

Graphical Abstract
Effects of robot-assisted therapy on upper limb and cognitive function in patients with stroke: study protocol of a randomized controlled study
Authors: Wang Yana , Ye Mingzhu , Tong Yujie , Xiong Li , Wu Xuejiao , Geng Chao , Zhang Wen , Dai Ziqi , Tian Wei , Rong Jifeng
Published: June 2022

Background

Impairments in upper limb motor function and cognitive ability are major health problems experienced by stroke patients, necessitating the development of novel and effective treatment options in stroke care. The aim of this study is to examine the effects of robot-assisted therapy on improving upper limb and cognitive functions in stroke patients.

Methods

This will be a single-blinded, 2-arm, parallel design, randomized controlled trial which will include a sample size of 86 acute and subacute stroke patients to be recruited from a single clinical hospital in Shanghai, China. Upon qualifying the study eligibility, participants will be randomly assigned to receive either robot-assisted therapy or conventional therapy with both interventions being conducted over a 6-week period in a clinical rehabilitation setting. In addition to comprehensive rehabilitation, the robot-assisted therapy group will receive a 30-min Armguider robot-assisted therapy intervention 5 days a week. Primary efficacy outcomes will include Fugl-Meyer Assessment for Upper Extremity (FMA-UE) and Mini-Mental Status Examination (MMSE). Other secondary outcomes will include Trail Making Test (TMT), Auditory Verbal Learning Test (AVLT), Digit Symbol Substitution Test (DSST), and Rey–Osterrieth Complex Figure Test (ROCFT). All trial outcomes will be assessed at baseline and at 6-week follow-up. Intention-to-treat analyses will be performed to examine changes from baseline in the outcomes. Adverse events will be monitored throughout the trial period.

Discussion

This will be the first randomized controlled trial aimed at examining the effects of robot-assisted therapy on upper limb and cognitive functions in acute and subacute stroke patients. Findings from the study will contribute to our understanding of using a novel robotic rehabilitation approach to stroke care and rehabilitation.

Trial registration

Chinese Clinical Trial RegistryChiCTR2100050856. Registered on 5 September 2021.
Phylogeographic dynamics of the arthropod vector, the blacklegged tick (Ixodes scapularis)
Authors: O’Keeffe Kayleigh R. , Oppler Zachary J. , Prusinski Melissa , Falco Richard C. , Oliver JoAnne , Haight Jamie , Sporn Lee Ann , Backenson P. Bryon , Brisson Dustin
Published: June 2022

Background

The emergence of vector-borne pathogens in novel geographic areas is regulated by the migration of their arthropod vectors. Blacklegged ticks (Ixodes scapularis) and the pathogens they vector, including the causative agents of Lyme disease, babesiosis and anaplasmosis, continue to grow in their population sizes and to expand in geographic range. Migration of this vector over the previous decades has been implicated as the cause of the re-emergence of the most prevalent infectious diseases in North America.

Methods

We systematically collected ticks from across New York State (hereafter referred to as New York) from 2004 to 2017 as part of routine tick-borne pathogen surveillance in the state. This time frame corresponds with an increase in range and incidence of tick-borne diseases within New York. We randomly sampled ticks from this collection to explore the evolutionary history and population dynamics ofI. scapularis. We sequenced the mitochondrial genomes of each tick to characterize their current and historical spatial genetic structure and population growth using phylogeographic methods.

Results

We sequenced whole mitochondrial genomes from 277 ticks collected across New York between 2004 and 2017. We found evidence of population genetic structure at a broad geographic scale due to differences in the relative abundance, but not the composition, of haplotypes among sampled ticks. Ticks were often most closely related to ticks from the same and nearby collection sites. The data indicate that both short- and long-range migration events shape the population dynamics of blacklegged ticks in New York.

Conclusions

We detailed the population dynamics of the blacklegged tick (Ixodes scapularis) in New York during a time frame in which tick-borne diseases were increasing in range and incidence. Migration of ticks occurred at both coarse and fine scales in the recent past despite evidence of limits to gene flow. Past and current tick population dynamics have implications for further range expansion as habitat suitability for ticks changes due to global climate change. Analyses of mitochondrial genome sequencing data will expound upon previously identified drivers of tick presence and abundance as well as identify additional drivers. These data provide a foundation on which to generate testable hypotheses on the drivers of tick population dynamics occurring at finer scales.

Graphical Abstract
Development and validation of a trans-ancestry polygenic risk score for type 2 diabetes in diverse populations
Authors: Ge Tian , Irvin Marguerite R. , Patki Amit , Srinivasasainagendra Vinodh , Lin Yen-Feng , Tiwari Hemant K. , Armstrong Nicole D. , Benoit Barbara , Chen Chia-Yen , Choi Karmel W. , Cimino James J. , Davis Brittney H. , Dikilitas Ozan , Etheridge Bethany , Feng Yen-Chen Anne , Gainer Vivian , Huang Hailiang , Jarvik Gail P. , Kachulis Christopher , Kenny Eimear E. , Khan Atlas , Kiryluk Krzysztof , Kottyan Leah , Kullo Iftikhar J. , Lange Christoph , Lennon Niall , Leong Aaron , Malolepsza Edyta , Miles Ayme D. , Murphy Shawn , Namjou Bahram , Narayan Renuka , O’Connor Mark J. , Pacheco Jennifer A. , Perez Emma , Rasmussen-Torvik Laura J. , Rosenthal Elisabeth A. , Schaid Daniel , Stamou Maria , Udler Miriam S. , Wei Wei-Qi , Weiss Scott T. , Ng Maggie C. Y. , Smoller Jordan W. , Lebo Matthew S. , Meigs James B. , Limdi Nita A. , Karlson Elizabeth W.
Published: June 2022

Background

Type 2 diabetes (T2D) is a worldwide scourge caused by both genetic and environmental risk factors that disproportionately afflicts communities of color. Leveraging existing large-scale genome-wide association studies (GWAS), polygenic risk scores (PRS) have shown promise to complement established clinical risk factors and intervention paradigms, and improve early diagnosis and prevention of T2D. However, to date, T2D PRS have been most widely developed and validated in individuals of European descent. Comprehensive assessment of T2D PRS in non-European populations is critical for equitable deployment of PRS to clinical practice that benefits global populations.

Methods

We integrated T2D GWAS in European, African, and East Asian populations to construct a trans-ancestry T2D PRS using a newly developed Bayesian polygenic modeling method, and assessed the prediction accuracy of the PRS in the multi-ethnic Electronic Medical Records and Genomics (eMERGE) study (11,945 cases; 57,694 controls), four Black cohorts (5137 cases; 9657 controls), and the Taiwan Biobank (4570 cases; 84,996 controls). We additionally evaluated a post hoc ancestry adjustment method that can express the polygenic risk on the same scale across ancestrally diverse individuals and facilitate the clinical implementation of the PRS in prospective cohorts.

Results

The trans-ancestry PRS was significantly associated with T2D status across the ancestral groups examined. The top 2% of the PRS distribution can identify individuals with an approximately 2.5–4.5-fold of increase in T2D risk, which corresponds to the increased risk of T2D for first-degree relatives. The post hoc ancestry adjustment method eliminated major distributional differences in the PRS across ancestries without compromising its predictive performance.

Conclusions

By integrating T2D GWAS from multiple populations, we developed and validated a trans-ancestry PRS, and demonstrated its potential as a meaningful index of risk among diverse patients in clinical settings. Our efforts represent the first step towards the implementation of the T2D PRS into routine healthcare.
How can community-based (re)engagement initiatives meet the needs of ‘NEET’ young people? Findings from the theory gleaning phase of a realist evaluation in Sweden
Authors: Jonsson Frida , Gotfredsen Anne C. , Goicolea Isabel
Published: June 2022

Objective

There has been a lack of systematic and theoretically underpinned evaluations, internationally and in Sweden, of local multi-component initiatives delivered outside public employment services and formal education systems to young people who are not in employment, education or training (‘NEETs’). To bridge this knowledge gap, the objective of this study was to present findings from the theory gleaning phase of a realist evaluation aimed at assessing how Swedish community-based initiatives may work to (re)engage vulnerable ‘NEET’ young people in education or employment, under what conditions and why.

Results

Based on insights gleaned and synthesised from various sources, three candidate programme theories were elicited drawing attention to the importance of community-based initiatives in Sweden adopting a ‘caring approach’, a ‘capability approach’ and a ‘collaborative approach’ to (re)engage ‘NEET’ young people in education or employment. While limited to the initial phase of theory gleaning, the study provides valuable insights into the potential functioning of (re)engagement initiatives directed towards vulnerable ‘NEETs’ in addition to increasing the transparency of a highly iterative research project.
Experience and results after the implementation of a radiology day unit in a reference hospital
Authors: Roson Nuria , Antolin Andreu , Mast Richard , Sanchéz-Tirado Cristina , Griñón Jesús , Andreu Jordi , Perez Lafuente Mercedes , Tomasello Alejandro , Escobar Manuel
Published: June 2022

Background

Interventional radiological procedures have significantly increased in recent years. Most of them are minimally invasive and require a short hospitalization, mainly done in other non-radiological units nowadays. Limited bed availability and high occupancy rates in these units create longer waiting lists and cancellations. The aim of this retrospective study is to assess the creation and functioning of a Radiology Day Unit (RDU) and evaluating its outcomes. For this purpose, data about interventional procedures and its complications, incidents, patient safety, quality and satisfaction rates were collected from May 2018 to December 2020, and posteriorly analyzed to evaluate its implementation.

Results

During the assessed period, 3841 patients were admitted into the RDU, with a net increase of 13% and 26% in the second and third year, respectively. Procedures performed by the Abdominal Radiology section were the most frequent (76–85%) followed by Interventional Vascular Radiology and Thoracic Radiology. Complication rates were low (1.5%) and most of them were self-limited and managed in the own department. Waiting lists were significantly reduced, from 2 months to 1 week in case of procedures performed by the Abdominal Radiology section. Patient satisfaction was higher than 80% in all the items evaluated with a global satisfaction of 93%.

Conclusion

The RDU in our hospital has become a vital section for the management and post-procedure caring of patients undergoing interventional procedures in the Radiology Service with low complication rates and overall high levels of quality and patient safety, allowing the reduction of waiting lists and occupancy rates.
KCNQ1-deficient and KCNQ1-mutant human embryonic stem cell-derived cardiomyocytes for modeling QT prolongation
Authors: Song Yuanxiu , Guo Tianwei , Jiang Youxu , Zhu Min , Wang Hongyue , Lu Wenjing , Jiang Mengqi , Qi Man , Lan Feng , Cui Ming
Published: June 2022

Background

The slowly activated delayed rectifier potassium current (IKs) mediated by the KCNQ1 gene is one of the main currents involved in repolarization. KCNQ1 mutation can result in long-QT syndrome type 1 (LQT1). IKs does not participate in repolarization in mice; thus, no good model is currently available for research on the mechanism of and drug screening for LQT1. In this study, we established a KCNQ1-deficient human cardiomyocyte (CM) model and performed a series of microelectrode array (MEA) detection experiments on KCNQ1-mutant CMs constructed in other studies to explore the pathogenic mechanism of KCNQ1 deletion and mutation and perform drug screening.

Method

KCNQ1 was knocked out in human embryonic stem cell (hESC) H9 line using the CRISPR/cas9 system. KCNQ1-deficient and KCNQ1-mutant hESCs were differentiated into CMs through a chemically defined differentiation protocol. Subsequently, high-throughput MEA analysis and drug intervention were performed to determine the electrophysiological characteristics of KCNQ1-deficient and KCNQ1-mutant CMs.

Results

During high-throughput MEA analysis, the electric field potential and action potential durations in KCNQ1-deficient CMs were significantly longer than those in wild-type CMs. KCNQ1-deficient CMs also showed an irregular rhythm. Furthermore, KCNQ1-deficient and KCNQ1-mutant CMs showed different responses to different drug treatments, which reflected the differences in their pathogenic mechanisms.

Conclusion

We established a human CM model with KCNQ1 deficiency showing a prolonged QT interval and an irregular heart rhythm. Further, we used various drugs to treat KCNQ1-deficient and KCNQ1-mutant CMs, and the three models showed different responses to these drugs. These models can be used as important tools for studying the different pathogenic mechanisms of KCNQ1 mutation and the relationship between the genotype and phenotype of KCNQ1, thereby facilitating drug development.
Application of stem cells and exosomes in the treatment of intracerebral hemorrhage: an update
Authors: Zhou Jian-feng , Xiong Yu , Kang Xiaodong , Pan Zhigang , Zhu Qiangbin , Goldbrunner Roland , Stavrinou Lampis , Lin Shu , Hu Weipeng , Zheng Feng , Stavrinou Pantelis
Published: June 2022

Non-traumatic intracerebral hemorrhage is a highly destructive intracranial disease with high mortality and morbidity rates. The main risk factors for cerebral hemorrhage include hypertension, amyloidosis, vasculitis, drug abuse, coagulation dysfunction, and genetic factors. Clinically, surviving patients with intracerebral hemorrhage exhibit different degrees of neurological deficits after discharge. In recent years, with the development of regenerative medicine, an increasing number of researchers have begun to pay attention to stem cell and exosome therapy as a new method for the treatment of intracerebral hemorrhage, owing to their intrinsic potential in neuroprotection and neurorestoration. Many animal studies have shown that stem cells can directly or indirectly participate in the treatment of intracerebral hemorrhage through regeneration, differentiation, or secretion. However, considering the uncertainty of its safety and efficacy, clinical studies are still lacking. This article reviews the treatment of intracerebral hemorrhage using stem cells and exosomes from both preclinical and clinical studies and summarizes the possible mechanisms of stem cell therapy. This review aims to provide a reference for future research and new strategies for clinical treatment.
Raising attainment for low-scoring students through quectures: an analysis of achievement and engagement with personalised learning in lectures
Authors: McQueen Heather A. , Colegrave Nick
Published: June 2022

Background

Quectures are flipped lectures with embedded ‘quecture questions’, which employ metacognitive reflection as an active learning intervention. Quecture questions are students’ own questions, identified and constructed by students around learning objectives during lectures. The quecture question intervention aims to support each student to engage better with their learning and to work at an individually appropriate level, and is accessible to all students irrespective of learning background. This research explores engagement and performance of students using the intervention, with a focus on those who traditionally receive low scores, to measure the effectiveness of quecture questions.

Results

Accumulated data demonstrate that student engagement with quecture questions is associated with improved learning on wider topics than those on which the intervention was used, as evidenced by improved overall course scores. Students who participate minimally within other elements of the course but who do submit their own quecture questions gain disproportionate benefit. The improved performance benefits of engagement with quecture questions are most marked for students with low prior scores. Students originating from the same country as our university and those whose parents did not attend university represent typically low-scoring demographic groups with low participation levels who might potentially benefit from the quecture strategy. However, lack of engagement with the intervention is also prevalent in these student groups precluding unengaged students from benefitting.

Conclusions

Quecture questions represent a simple yet effective intervention for improving learning in lectures. Broad learning benefits suggest improved learning habits, and support the notion that the intervention leads to students assuming increased responsibility for their own learning. The use of quecture questions generated most benefit to low-scoring students, validating the intervention as a useful tool with which to address learning inequities. The quecture question intervention readily adapts to suit online learning and represents an ideal first step for busy instructors wishing to adapt their lectures towards a more student-centred approach to learning.
The impact of protected areas on poverty: evidence from Chile
Authors: Vilela Thais , Harb Alfonso Malky , Vergara Carla Mendizábal
Published: June 2022

In this paper, we estimate the causal relationship between protected areas and poverty in Chile from 1982 to 2002. Chile is part of the coalition of countries committed to protecting 30% of the planet by 2030; a decision that implies increasing the number of protected areas in the country. As a result of this decision, grows the national debate about the potential impacts of protected areas on the economy and society. By estimating the causal effect of protected areas on poverty, we aim to contribute to this debate in Chile. We use panel data and a quasi-experimental approach to estimate the causal effect. We find that establishing a protected area covering at least 17% of a unit’s terrestrial area causes a reduction of 0.216 standard deviations in the poverty index. This result is not sensitive to arbitrary implementation choices. Additionally, we show that the effect is driven by the Patagonia region, the part of Chile with the largest amount of new protected areas during the time frame of this study. Besides showing the benefits of protected areas to society, we hope the findings presented here might also be used to attract new investments and financial support to protected areas currently underfunded in Chile.
Cardiac dysfunction in patients with end-stage liver disease, prevalence, and impact on outcome: a comparative prospective cohort study
Authors: Al Atroush Hatem H. , Mohammed Khaled H. , Nasr Fatma M. , Al Desouky Mohammed I. , Rabie Mohammed A.
Published: June 2022

Background

Without firm diagnostic criteria, the exact prevalence of cirrhotic cardiomyopathy still remains unknown. Its estimation is rather a difficult task as the disease is generally latent and shows itself only when the patient is subjected to overt stress such as body position changes, exercise, drugs, hemorrhage, and surgery. In this study, we aim to assess cardiac dysfunction in patients with end-stage liver disease, study the correlation between cardiac dysfunction and Child-Pugh classification of patients with liver cell failure, and study the prevalence and impact of cardiac dysfunction on the clinical outcome of patients with child B and child C liver disease.

Results

Diastolic dysfunction was more prevalent among the patients’ group (p < 0.001). It was absent in 28 (70%) of control group, with grade 1 diastolic dysfunction in 12 (30%). Only one patient (2.5%) had no diastolic dysfunction, 21 patients (52.5%) had grade 1 diastolic dysfunction, 12 (30%) patients had grade 2 diastolic dysfunction, and 6 patients (15%) had grade 3 diastolic dysfunction. QTc interval was significantly prolonged in the patients’ group when compared to controls (p < 0.001). Echocardiographic parameters and QTc interval were comparable in child B and child C patients. All patients were followed up for a period of 3 months. Sixteen of 40 patients died in this period of time. Only child classification was found to significantly predict mortality, and patients with child C liver cirrhosis had worse survival when compared to patients with child B liver cirrhosis.

Conclusion

Most of the patients had cardiac dysfunction, mainly diastolic dysfunction (87.5%). The study detected the prevalence of diastolic dysfunction among end-stage liver disease when measuring E/É using TDI which proved to be more accurate than E/A ratio. Diastolic dysfunction is proved to be the most sensitive parameter in the diagnosis of cirrhotic cardiomyopathy, being the most parameter affected early. No correlation was found between cardiac dysfunction and the severity of hepatic illness, but the severity of hepatic illness affects the outcome rather than cardiac dysfunction.
Nucleolin loss of function leads to aberrant Fibroblast Growth Factor signaling and craniofacial anomalies
Authors: Dash Soma , Trainor Paul A.
Published: June 2022

Ribosomal RNA (rRNA) transcription and ribosome biogenesis are global processes required for growth and proliferation of all cells, yet perturbation of these processes in vertebrates leads to tissue-specific defects termed ribosomopathies. Mutations in rRNA transcription and processing proteins often lead to craniofacial anomalies; however, the cellular and molecular reasons for these defects are poorly understood. Therefore, we examined the function of the most abundant nucleolar phosphoprotein, Nucleolin (Ncl), in vertebrate development. ncl mutant (ncl−/−) zebrafish present with craniofacial anomalies such as mandibulofacial hypoplasia. We observed that ncl−/− mutants exhibited decreased rRNA synthesis and p53-dependent apoptosis, consistent with a role in ribosome biogenesis. However, we found that Nucleolin also performs functions not associated with ribosome biogenesis. We discovered that the half-life of fgf8a mRNA was reduced in ncl−/− mutants, which perturbed Fgf signaling, resulting in misregulated Sox9a-mediated chondrogenesis and Runx2-mediated osteogenesis. Consistent with this model, exogenous FGF8 treatment significantly rescued the cranioskeletal phenotype in ncl−/− zebrafish, suggesting that Nucleolin regulates osteochondroprogenitor differentiation. Our work has therefore uncovered tissue-specific functions for Nucleolin in rRNA transcription and post-transcriptional regulation of growth factor signaling during embryonic craniofacial development.
Decoding the genetics of rare disease: an interview with Monkol Lek
Authors: Lek Monkol
Published: June 2022

Monkol Lek, Assistant Professor at Yale University School of Medicine, and Associate Editor at Disease Models & Mechanisms, dedicates his research to finding a genetic diagnosis and improving treatments for rare disease patients. As he originally studied computer engineering at the University of New South Wales in Sydney, Australia, he now utilises computational methods to optimise large-scale genetic studies, provide globally accessible resources for genetic research communities and, importantly, resolve diagnostic odysseys for rare disease patients. Monkol completed his PhD in Prof. Kathryn North's lab at the University of Sydney, studying the genetics of muscle strength and performance, and then continued his investigation of muscle disease in Prof. Daniel MacArthur's lab at Massachusetts General Hospital and the Broad Institute. During his postdoc, he led several large-scale studies aimed at distinguishing pathogenic from benign variants, including the Exome Aggregation Consortium (ExAC) project ( Lek et al., 2016). Monkol established his own lab at Yale University School of Medicine, which continues to improve the diagnosis and treatment of rare muscle disease, and also focuses on underserved populations, whose genetic mutations are not as well characterised as those of European ancestry. In this interview, Monkol discusses how his own diagnosis with limb girdle muscular dystrophy has shaped his career and what he envisions for the future of genetic research in rare disease.
Bats actively modulate membrane compliance to control camber and reduce drag
Authors: Cheney Jorn A. , Rehm Jeremy C. , Swartz Sharon M. , Breuer Kenneth S.
Published: June 2022

Bat wing skin is exceptionally compliant and cambers significantly during flight. Plagiopatagiales proprii, arrays of small muscles embedded in the armwing membrane, are activated during flight and are hypothesized to modulate membrane tension. We examined the function of these muscles using Jamaican fruit bats, Artibeus jamaicensis. When these muscles were paralyzed using botulinum toxin, the bats preferred flight speed decreased and they were unable to fly at very low speeds. Paralysis of the plagiopatagiales also resulted in increased armwing camber consistent with a hypothesized role of modulating aeroelastic interactions. Other compensatory kinematics included increased downstroke angle and increased wingbeat amplitude. These results are consistent with the bats experiencing increased drag and flight power costs associated with the loss of wing-membrane control. Our results indicate that A. jamaicensis likely always employ their wing membrane muscles during sustained flight to control camber and to enhance flight efficiency over a wide flight envelope.
Lignin Derived Carbon Electrodes for Hydrocarbon Formation by Electrochemical Reduction of Carbon Dioxide
Authors: Kato Takafumi , Yoda Takuya , Yoshihara Naoki
Published: June 2022

Biomass-derived carbon materials have attracted interest as metal-free electrode candidates for electrochemical reactions. Hydrocarbon formation (i.e., methane and ethane) using the electrochemical reduction of carbon dioxide (CO2ER) on as-synthesized sulfur (S) containing lignin derived carbon electrodes was demonstrated. The current efficiencies of hydrocarbon products by CO2ER were found to be dependent on the carbonized temperature and a thermal treatment scheme, resulting in different surface structures and chemical composition of S species.
The Impact of Health on Labor Market Outcomes: Evidence from a Large-Scale Health Experiment
Authors: Stephens Melvin , Toohey Desmond
Published: June 2022

While economists have posited that health investments increase earnings, isolating the causal effect of health is challenging due to reverse causality and unobserved heterogeneity. We examine the labor market effects of a randomized controlled trial, the Multiple Risk Factor Intervention Trial (MRFIT), which monitored nearly 13,000 men for over six years. We find that this intervention, which provided a bundle of treatments to reduce coronary heart disease mortality, increased earnings and family income. We find few differences in estimated gains by baseline health and occupation characteristics. (JEL I12, J24, J31)
The Side Effects of Immunity: Malaria and African Slavery in the United States
Authors: Esposito Elena
Published: June 2022

This paper documents the role of malaria in the diffusion of African slavery in the United States. The novel empirical evidence reveals that the introduction of malaria triggered a demand for malaria-resistant labor, which led to a massive expansion of African enslaved workers in the more malaria-infested areas. Further results document that among African slaves, more malaria-resistant individuals—i.e., those born in the most malaria-ridden regions of Africa—commanded significantly higher prices. (JEL I12, J23, J47, N31, N37, N91)
Do Doctors Improve the Health Care of Their Parents? Evidence from Admission Lotteries
Authors: Artmann Elisabeth , Oosterbeek Hessel , van der Klaauw Bas
Published: June 2022

To assess the importance of unequal access to medical expertise and services, we estimate the causal effects of having a child who is a doctor on parents' mortality and health care use. We use data from parents of almost 22,000 participants in admission lotteries to medical school in the Netherlands. Our findings indicate that informal access to medical expertise and services is not an important cause of differences in health care use and mortality. (JEL H51, I11, I12, I14, I18)
Why Have College Completion Rates Increased?
Authors: Denning Jeffrey T. , Eide Eric R. , Mumford Kevin J. , Patterson Richard W. , Warnick Merrill
Published: June 2022

We document that college completion rates have increased since the 1990s, after declining in the 1970s and 1980s. We find that most of the increase in graduation rates can be explained by grade inflation and that other factors, such as changing student characteristics and institutional resources, play little or no role. This is because GPA strongly predicts graduation, and GPAs have been rising since the 1990s. This finding holds in national survey data and in records from nine large public universities. We also find that at a public liberal arts college grades increased, holding performance on identical exams fixed. (JEL I23)
Acetabular paralabral cysts demonstrating perineural propagation
Authors: Hynes John , Chabra Avneesh , Guirguis Mina , Kavanagh Eoin
Published: June 2022

Objective:

Acetabular paralabral cysts are common and are almost always associated with labral tears. Uncommonly, they extend into the periacetabular soft tissues or may propagate along peripheral nerves causing pain and hip dysfunction. The aim was to evaluate the clinical and MRI presentations of such cases including perineural propagation.

Methods:

Retrospective cross-sectional study with a search of electronic health records for cases of acetabular paralabral cysts demonstrating perineural propagation was performed. Clinical and MR imaging features were tabulated after re-review by experienced musculoskeletal radiologists, and available outcomes were recorded. Descriptive statistics were performed.

Results:

14 cases were recorded. The mean age was 56.9 years (range = 30–79 years) and female:male ratio was 1:2.6. The commonest presenting complaint was hip pain (10/14, 71.4%). Other complaints included groin pain, perineal pain and hip dysfunction. No symptoms were attributed to the acetabular paralabral cyst in 3/14 patients (21.4%). None had foot drop. The cysts were multilocular in all cases and were homogenously T2 hyperintense in 13/14 (92.9%). Labral tears were identified in 11/14 cases (78.6%). The sciatic nerve was most commonly involved in 5/14 cases (35.7%) with the obturator, medial femoral cutaneous nerve, femoral nerve, superior and inferior gluteal nerves also affected.

No intervention was undertaken in 9/14 cases (64.3%). 5/14 (35.7%) underwent image guided aspiration and corticosteroid injection. 4/5 such patients reported reduced pain following the procedure.

Conclusion:

Paralabral cysts demonstrating perineural propagation are uncommon and exhibit varied presentations. Most patients who underwent image-guided or surgical interventions reported an improvement in symptoms.

Advances in knowledge.:

This is the first description of a series of patients with acetabular paralabral cysts demonstrating perineural propagation in the literature. A comprehensive description of their clinical and imaging characteristics and interventions/outcomes where relevant is provided.
Breast cancer risk predictions by birth cohort and ethnicity in a population-based screening mammography program
Authors: Epp Joyce , Rajapakshe Rasika
Published: June 2022

Objectives:

To examine whether birth cohorts affect the risk of breast cancer for East Asian, First Nations, African, South Asian and Caucasian ethnicities in British Columbia (BC).

Methods:

We used Cox PH models adjusted for well-known risk factors, such as age, breast density, mammographic features on false positives, and family history, to examine risk of breast cancer among East Asian, First Nations, African and South Asian ethnicities, relative to Caucasian, across three birth cohorts.

Results:

There were 813,280 participants and 11,166 in situ and invasive breast cancer diagnoses. East Asians screened in BC were found to have a lower risk of breast cancer in the birth cohort born pre-1946 compared to Caucasian, but there was no statistically significant decrease for East Asians born after 1946. First Nations had an increased risk of breast cancer compared with Caucasian for all birth cohorts ranging from 1.1 to 2.0x the risk, which was statistically significant for those born after 1965. South Asians showed a statistically significant decrease in risk ranging from 0.58 to 0.81x lower compared with Caucasians for all birth cohorts.

Conclusion:

Risk of breast cancer for South Asians living in BC was found to be lower than Caucasians for each birth cohort examined, while East Asians had a comparable risk of breast cancer, First Nations had a consistently higher risk than Caucasians.

Advances in knowledge:

When accounting for birth cohort, compared to Caucasians, South Asians have a decreased risk, First Nations have an increased risk, and East Asians have a similar risk of breast cancer.
Prostatic artery occlusion versus prostatic artery embolisation for the management of benign prostatic hyperplasia: early results in a canine model
Authors: Lucas-Cava Vanesa , Sánchez-Margallo Francisco Miguel , Dávila-Gómez Luis , Lima-Rodríguez Juan Rafael , Sun Fei
Published: June 2022

Objective:

To compare the technical efficacy and safety between prostatic artery occlusion (PAO) with ethylene vinyl alcohol copolymer (EVOH) and prostatic artery embolizsation (PAE) with microspheres in a canine model.

Methods:

17 adult male beagles underwent PAO (n = 7) with Onyx-18 or PAE (n = 10) with microspheres (300–500 µm). To evaluate the primary outcomes (technical efficacy and safety), MRI evaluations were performed immediately before and 1 week, 2 weeks, and 1 month after procedures to document prostate volume (PV); and all dogs were inspected for procedure-related complications during 1 month follow-up. The secondary outcomes included the prostate ischaemia size detected by MRI and recanalisation of prostatic artery by follow-up angiography. Differences between groups were statistically analysed.

Results:

Both procedures were bilaterally successful in all animals. Compared with PAE, the mean fluoroscopy time (23.80 vs 36.24 min, p = 0.014) and radiation dose (68.19 vs 125.26 mGy, p = 0.003) were significantly less in PAO procedure. The mean percentage of PV change significantly decreased in both groups at 2 weeks (30.71% vs  37.89%) and 1 month (56.41% %vs 55.56%) after PAO and PAE respectively), without significant differences between groups at either time point. No major complications were observed except one animal after PAO with transient haematuria and acute urinary retention. The mean prostate ischaemia induced by PAO was significant greater compared with PAE at 1 week (43.44% vs 18.91%, p=0.001). PAO with EVOH is technically feasible and with comparable efficacy and safety with PAE. There are possible benefits to PAO over PAE.

Advances in knowledge:

A new technical modification of the PAE consisting of the use of liquid embolic agent to occlude the prostatic artery trunk and its branches has been developed in pre-clinical study, showing to be an effective and safe procedure which can induce a significant prostate shrinkage for the management of symptomatic benign prostatic hyperplasia in patients. In addition, the findings have showed a similar therapeutic effect comparable with the conventional PAE using microspheres.
Comparison of outcome of Ponseti method with traditional clubfoot treatment in children up to five years of age at tertiary care hospital
Authors: Yaqeen Ayesha , Sidra Hafiza , Ijaz Muhammad Abdullah , Ijaz Muhammad Muneeb
Published: June 2022

Objectives: To compare the outcomes of Ponseti treatment with the traditional treatment method for clubfoot.

Methods: A cross-sectional comparative study was conducted at the orthopedic department of Nishtar Medical Hospital & University Multan for one year. The study included 40 children (29 clubfeet) treated with conventional treatment (pre-Ponseti group) who were compared with 55 Ponseti-treated children (72 clubfeet) (Ponseti group). All children were aged under five years. The traditional treatment involved casting and surgery (if required). All the participants were evaluated by a single orthopedic surgeon. The questionnaire was administered to the parents to collect relevant data. X-ray studies were conducted of all feet and patients’ records were checked for surgical history.

Results: Children in the pre-Ponseti group had a significantly higher number of surgeries (54) than those in Ponseti group eight. According to the reports of the parents, children in Ponseti group had significantly better motion in the ankle, lesser pain, and higher satisfaction (p<0.05.whereas, the pre-Ponseti group had a higher incidence of moderate or severe talar flattening rate (p=0.01).

Conclusion: Ponseti treatment is better than earlier treatment in terms of lesser need of surgeries, higher flexibility of ankle or foot, and lower presence of X-ray guided talar flattening.

doi: https://doi.org/10.12669/pjms.38.6.5519

How to cite this:Yaqeen A, Sidra H, Ijaz MA, Ijaz MM. Comparison of outcome of Ponseti method with traditional clubfoot treatment in children up to five years of age at tertiary care hospital. Pak J Med Sci. 2022;38(6):---------. doi: https://doi.org/10.12669/pjms.38.6.5519

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Deflating abdominal pseudocyst causing temporary normalization of ventriculoperitoneal shunt malfunction
Authors: Algahtany Mubarak Ali , Kojadinovic Zeljko , Algahtany Aws
Published: June 2022

Ventriculoperitoneal shunt (VPS)-related abdominal pseudocyst (APC) is a rare cause of shunt malfunction. Variable VPS function due to APC has not been described before. A 21-year-old male with hydrocephalus and bilateral VPS presented with a right-sided shunt malfunction. After a routine abdominal ultrasound (US), that proved to be unremarkable, the patient had a clinical and radiological improvement followed by a relapse. An abdominal computed tomography scan subsequently showed an APC around the peritoneal catheter tip. Laparoscopic intervention on the APC cured the shunt malfunction. We believe that the APC emptied during the compression involved while performing the abdominal US. The pseudocyst collapse led to missing it on the abdominal US and explains the short-lived clinical and radiological improvement. We introduce the concept of APC-related variable VPS function, discuss the possible mechanisms by which the pseudocyst deflated, and make suggestions toward this diagnostic problem.

Key Messages: A collapsible abdominal pseudocyst could result in a variable ventriculoperitoneal shunt function. Starting the abdominal ultrasound examination over the location of the peritoneal catheter tip may overcome the collapse. Contrasted computed tomography is superior to ultrasound in diagnosing the pseudocyst.

Abbreviations:APC: Abdominal pseudocyst, CSF: Cerebrospinal fluid, CT: Computed tomography,MRI: Magnetic resonance imaging, US: Ultrasound, VPS: Ventriculoperitoneal shunt.

doi: https://doi.org/10.12669/pjms.38.6.6278

How to cite this:Algahtany MA, Kojadinovic Z, Algahtany A. Deflating abdominal pseudocyst causing temporary normalization of ventriculoperitoneal shunt malfunction. Pak J Med Sci. 2022;38(6):---------. doi: https://doi.org/10.12669/pjms.38.6.6278

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.