bluuebunny/crossref_metadata_2025 huggingface dataset:
DENTAL ASSISTANCE TO MILITARY PERSONNEL OF THE ARMED FORCES OF UKRAINE
Authors: Lavrin O. Ya. , Avdeev O. V. , Romanjuk N. Ye. , Bedenyuk O. A.
Published: June 2022

Background. At present, the formation of military units of the Armed Forces of Ukraine during mobilization takes place with underlying high dental morbidity of the population of the country.
Objective. The aim of this research was to study dental health of the personnel of military units and the problem of providing dental care to military personnel according to the analysis of modern scientific literature.
Methods. The following research methods were used to analyse dental care for military personnel, namely: bibliographic, analytical, systems approach.
Results. Hygiene of the oral cavity is mandatory in military units and should be routinely carried out. It was found that the main reason for seeking dental care among military personnel was treatment of major dental diseases. A low number of military personnel seeking for dental preventive examination was noted that proved a low level of primary prevention among this category of people.
Conclusions. Therefore, the obtained data on the state of dental health of military personnel require a purposeful approach to organization of prophylaxis and prevention of complications through professional hygiene and early prosthetics.
THE EFFECT OF MICROCRYSTALLINE CELLULOSE ON THE MICROFLORA OF THE COLON
Authors: Koval D. B. , Malyarchuk H. R. , Levenets O. O.
Published: June 2022

Background. Nowadays, much attention is paid to enterosorption methods that allow cleansing the internal organs and removing extraneous substances out of the body of a sick person.
Objective. The aim of the research was to study the effect of microcrystalline cellulose on the microflora of the large intestine.
Methods. The study was performed on 50 white laboratory Wistar rats weighing 180-270 g, which were divided into control and experimental groups. The experimental group was daily administered with microcrystalline cellulose at a dose of 500 mg/kg. The study followed ethical standards and recommendations for the humanization of work with laboratory animals according to the “European Convention for the protection of vertebrate animals used for experimental and other purposes” (Strasbourg, 1986, 2010), as well as the requirements of the Commission on Bioethics of I. Horbachevsky Ternopil National Medical University (Minutes No. 66, dated November 01, 2021). The first group involved the intact rats on standard diet, the second – the rats, which received normal feeding of microcrystalline cellulose.
Results. In the feces of the experimental white rats treated with microcrystalline cellulose, the level of Escherichia coli in the large intestine decreased by 22 and 25%. The number of these microorganisms increased by 20% in 7 days and by 14% in 14 days. The content of epidermal staphylococci in the stool decreased by 10% on the 7th day of administration. Microcrystalline cellulose increased the number of Staphylococcus aureus by 12%, but decreased the number of enterococci in the feces by 28%. In 7-14 days of the experiment, the content of these bacteria did not change significantly in the colon. In relation to anaerobic microorganisms – bacteroides and clostridia, this supplement caused a slight increase in the number of bacteroides – by 8.64% and the number of clostridia – by 11.54% on the 14th day. The content of fungi of the Candida genus on the 7th and 14th day increased by 8.3%.
Conclusions. In the 2nd period of the study, the microbiome of intestinal contents worsened: the process of dysbacteriosis increased, which was manifested by a significant increase in the number of Proteus spp., Staphylococcus aureus, anaerobes (bacteroides, clostridia) and Candida spp., as well as decreased Escherichia coli and Enterococci.
HISTOPATHOLOGICAL PROFILE OF GASTROINTESTINAL NEUROENDOCRINE TUMORS IN A TERTIARY CARE HOSPITAL
Authors: Abbas F. , Beigh A. , Khuroo M. , Farooq S. , Khuroo N. , Tazeen S.
Published: June 2022

Background. Recently there has been a lot of discussion about the terminology and classification of neuroendocrine tumours of the gastrointestinal tract. The WHO has recommended a change of terminology and classification of these tumours. In 2019 a significant update was done in the WHO classification of neuroendocrine tumours of GIT in which neuroendocrine carcinomas (NECs) are all considered high-grade tumours. Previously, grade 1 and 2 tumours were regarded as neuroendocrine tumours (NETs) and grade 3 neoplasms as NECs. The new classification avoids confusion between these two clinically and molecularly distinct notions.
Objective. The aim of the research was to study GI neuroendocrine neoplasms and classify them as per location and Histopathological classification of GI neuroendocrine neoplasms according to the recent WHO classification. To use IHC whenever and wherever required for categorization of GI NET’s.
Methods. Over a period of 15 years, a total of 85 cases of neuroendocrine neoplasms of GIT were studied. The histopathological material of patients was reviewed and histopathological diagnosis confirmed. Paraffin embedded tissue blocks were used to study and review the material. Sections from tissue blocks were stained. Five-micron sections were cut and stained. The sections were stained using DAKO LSAB-2® system HRP glass slides coated with 0.5% poly-lysine.
Results. Out of 85 cases 40 involved male and 45 female patients. The mean age was 46.4 years; age range 9-85 years. In our study, appendix 24 (28.23%) and stomach 11 (12.95%) were the commonest sites of primary involvement followed by colon (10), ileum (10), duodenum (5), GE junction (5), jejunum (3), oesophagus (2), rectum (2) and gall bladder (1). Metastasis to the liver were observed in 12 patients with known and unknown primary diagnosis. Based on the latest WHO classification 5 patients were classified under NECs and the rest under NETs.
Conclusions. Neuroendocrine tumours (NETs) are uncommon malignancies of GIT. Appendix followed by stomach was the most common anatomical site. NET Grade 1 was the most common histological type. IHC markers NSE, Synaptophysin and Chromogranin can be used in diagnosis of NETs.
EVALUATION OF IMMUNOBLOT RESULTS FOR DETERMINATION OF ANTIBODIES TO LYME DISEASE PATHOGENS IN CHILDREN OF TERNOPIL REGION
Authors: Nykytyuk S. O. , Klymnyuk S. I. , Klishch I. M. , Levenets S. S.
Published: June 2022

Background. Lyme disease (LD) is a multisystem disorder caused by Borrelia burgdorferi and other similar tick-borne Borrelia.
Objective. The aim of the research was to compare the results of the serological examination of children with different forms of Lyme disease.
Methods. We observed the group of children (n=178) aged 1 to 14 years who were bitten by ticks. The control group consisted of 30 healthy children. Ticks were identified using a stereomicroscopic SEO system which included a stereomicroscope, a colour digital camera and a photoadapter. B. burgdorferi sensu lato (sl) (B. burgdorferi sensu stricto, B. afzeliі and B. garinii), B. miyamotoi, A. phagocytophilum DNA in blood were determined by real-time PCR. Baseline investigations related to clinical and immunological studies, including ELISA and Immunoblot, were performed.
Results. The survey covered 178 child parents bitten by ticks. Borrelia burgdorferi sensu lato (B. afzelii, B. burgdorferi sensu stricto and B. garinii), B. miyamotoi and A. phagocytophilum were identified. Serological results in children with different forms of Lyme disease were compared.
Conclusions. It is established that B. burgdorferi sensu lato; B. miyamotoi; and A. phagocytophilum are pathogens that cause erythema migrans in children. The presence of specific IgG (only positive results) to B. burgdorferi s.l. by immunoblot was confirmed in 83.8% of individuals who had positive and intermediate results in the ELISA test.
Large and Small Animal Models of Heart Failure With Reduced Ejection Fraction
Authors: Pilz Patrick M. , Ward Jennifer E. , Chang Wei-Ting , Kiss Attila , Bateh Edward , Jha Alokkumar , Fisch Sudeshna , Podesser Bruno K. , Liao Ronglih
Published: June 2022

Heart failure (HF) describes a heterogenous complex spectrum of pathological conditions that results in structural and functional remodeling leading to subsequent impairment of cardiac function, including either systolic dysfunction, diastolic dysfunction, or both. Several factors chronically lead to HF, including cardiac volume and pressure overload that may result from hypertension, valvular lesions, acute, or chronic ischemic injuries. Major forms of HF include hypertrophic, dilated, and restrictive cardiomyopathy. The severity of cardiomyopathy can be impacted by other comorbidities such as diabetes or obesity and external stress factors. Age is another major contributor, and the number of patients with HF is rising worldwide in part due to an increase in the aged population. HF can occur with reduced ejection fraction (HF with reduced ejection fraction), that is, the overall cardiac function is compromised, and typically the left ventricular ejection fraction is lower than 40%. In some cases of HF, the ejection fraction is preserved (HF with preserved ejection fraction). Animal models play a critical role in facilitating the understanding of molecular mechanisms of how hearts fail. This review aims to summarize and describe the strengths, limitations, and outcomes of both small and large animal models of HF with reduced ejection fraction that are currently used in basic and translational research. The driving defect is a failure of the heart to adequately supply the tissues with blood due to impaired filling or pumping. An accurate model of HF with reduced ejection fraction would encompass the symptoms (fatigue, dyspnea, exercise intolerance, and edema) along with the pathology (collagen fibrosis, ventricular hypertrophy) and ultimately exhibit a decrease in cardiac output. Although countless experimental studies have been published, no model completely recapitulates the full human disease. Therefore, it is critical to evaluate the strength and weakness of each animal model to allow better selection of what animal models to use to address the scientific question proposed.
Animal Models to Study Cardiac Arrhythmias
Authors: Blackwell Daniel J. , Schmeckpeper Jeffrey , Knollmann Bjorn C.
Published: June 2022

Cardiac arrhythmias are a significant cause of morbidity and mortality worldwide, accounting for 10% to 15% of all deaths. Although most arrhythmias are due to acquired heart disease, inherited channelopathies and cardiomyopathies disproportionately affect children and young adults. Arrhythmogenesis is complex, involving anatomic structure, ion channels and regulatory proteins, and the interplay between cells in the conduction system, cardiomyocytes, fibroblasts, and the immune system. Animal models of arrhythmia are powerful tools for studying not only molecular and cellular mechanism of arrhythmogenesis but also more complex mechanisms at the whole heart level, and for testing therapeutic interventions. This review summarizes basic and clinical arrhythmia mechanisms followed by an in-depth review of published animal models of genetic and acquired arrhythmia disorders.
CRISPR Modeling and Correction of Cardiovascular Disease
Authors: Liu Ning , Olson Eric N.
Published: June 2022

Cardiovascular disease remains the leading cause of morbidity and mortality in the developed world. In recent decades, extraordinary effort has been devoted to defining the molecular and pathophysiological characteristics of the diseased heart and vasculature. Mouse models have been especially powerful in illuminating the complex signaling pathways, genetic and epigenetic regulatory circuits, and multicellular interactions that underlie cardiovascular disease. The advent of CRISPR genome editing has ushered in a new era of cardiovascular research and possibilities for genetic correction of disease. Next-generation sequencing technologies have greatly accelerated the identification of disease-causing mutations, and advances in gene editing have enabled the rapid modeling of these mutations in mice and patient-derived induced pluripotent stem cells. The ability to correct the genetic drivers of cardiovascular disease through delivery of gene editing components in vivo, while still facing challenges, represents an exciting therapeutic frontier. In this review, we provide an overview of cardiovascular disease mechanisms and the potential applications of CRISPR genome editing for disease modeling and correction. We also discuss the extent to which mice can faithfully model cardiovascular disease and the opportunities and challenges that lie ahead.
Fifteenth-Century Melaka’s Networked Ports-of-Trade and Maritime Diasporas in the Bay of Bengal and Western Indian Ocean
Authors: Hall Kenneth R.
Published: June 2022

Internationally Western scholars have emphasized the importance of pre-fifteenth-century Western and Eastern Indian Ocean, South Asian, Bay of Bengal, South China; regional Java and wider Southeast Asia commercial, landed, maritime, and societal networking; and Islamic, Hindu, Theravada and Mahayana Buddhism. Notably where there were upstream agrarian hinterlands of early historical Southeast Asia polities, royal courts, temples, cultural centers, and traditional farming were relocated in the vulnerable regional downstream coastal ports-of-trade. This essay recenters the discussion of the changing role of Melaka’s trade ports and their engagement with maritime based trade as conducted by various regional populations.
The colonate in the Later Roman Empire
Authors: Sirks Boudewijn
Published: June 2022

In the fourth and fifth century there are people in the Roman empire who are bound to a particular estate in the sense that the estate owner can recall them and impose services. Their status, called the colonate, is low. Often it is assumed to have been widespread or even a general feature of a general change in agricultural exploitation. Various theories about its cause have been formulated: chronic indebtedness of farmers, fiscal reorganisations, emergence of large estates. However, already in the middle of the third century in Egypt a similar but private law contract existed, the paramonè. The insertion into the census of an estate under Diocletian gave it a public law aspect, making the estate owner now the contract partner. It implied a change in status for the colonus. It was consequently never a general phenomenon.
Pectinariidae (Annelida, Polychaeta) from the coastal waters of China, with description of new species and new records
Authors: ZHANG JINGHUAI , HUTCHINGS PAT , QIU JIAN-WEN
Published: June 2022

Pectinariidae Quatrefages, 1865 is widely distributed, and easily distinguished from other polychaetes by their characteristic semi-circular operculum with two rows of stout golden paleae and “ice-cream cone”-shaped tubes made of sand or shell fragments. A total of 387 specimens of pectinariids from the coastal waters of China were examined. Eleven species belonging to three genera of pectinariids were identified and described, including four new species (Amphictene jianqingi n. sp., Pectinaria lizhei n. sp., Pectinaria dayaensis n. sp., Pectinaria xiukaii n. sp.) and one new record (Pectinaria plurihamus Choi, Jung & Yoon, 2017). A key to genera of Pectinariidae and recorded species from Chinese waters is given. Based on partial sequences of five genes (COI, 16S rDNA, 18S rDNA, 28S rDNA and H3), the phylogenetic relationship of pectinariids is analyzed. The three new species Amphictene jianqingi n. sp., Pectinaria lizhei n. sp. and Pectinaria dayaensis n. sp. with molecular data are well supported. Three species of Lagis (L. koreni, L. bocki and L. plurihamus), five species of Pectinaria (P. dayaensis, P. dodeka, P. gouldii, P. lizhei and P. torquata), and three species of Amphictene (A. auricoma, A. alata and A. jianqingi) do not form a well supported clade, which requires more detailed analyses.
Developing Implementation Capacity of a State Education Agency to Improve Outcomes for Students With Disabilities
Authors: Kloos Eric , Nacik Ellen , Ward Caryn
Published: June 2022

The U.S. Department of Education’s Office of Special Education Programs has adopted a Results Driven Accountability (RDA) framework to support state education agencies (SEAs) in improving results for students with disabilities. RDA directed SEAs to focus on measurable outcomes. A leadership team in a large Midwestern state in the United States partnered with an institute of higher education implementation science purveyor team to systematically apply a particular approach, the Active Implementation Frameworks (AIFs), to build capacity, effectively implement, and scale an evidence-based program, Check & Connect, to improve statewide graduation rates for Black and American Indian students with disabilities. The presented case example illustrates how the SEA partners with local education agencies’ district teams to continuously measure and manage changes in (a) system capacity and (b) practice fidelity to improve graduation rate outcomes. Application of the AIFs in education, measured implementation progress and preliminary outcome data, and implications for policy for individuals with disabilities are discussed.
Risk of diabetes and the impact on preexisting diabetes in patients with lymphoma treated with steroid-containing immunochemotherapy
Authors: Baech Joachim , Severinsen Marianne Tang , Øvlisen Andreas K. , Frederiksen Henrik , Vestergaard Peter , Torp-Pedersen Christian , Jørgensen Judit , Clausen Michael Roost , Poulsen Christian B. , Brown Peter , Gang Anne Ortved , Pedersen Robert Schou , Ekström Smedby Karin , Eloranta Sandra , Jakobsen Lasse Hjort , El-Galaly Tarec Christoffer
Published: June 2022

First-line treatments for lymphomas often include high doses of prednisolone, but the risks of new-onset diabetes mellitus (DM) or worsening of preexisting DM following treatment with cyclic high dose corticosteroids is unknown. This cohort study matched non-Hodgkin lymphoma (NHL) patients treated with steroid-containing immunochemotherapy (ie, R-CHOP[-like] and R-CVP) between 2002 and 2015 to individuals from the Danish population to investigate the risks of new-onset DM. For patients with preexisting DM, the risks of insulin dependency and anthracycline-associated cardiovascular diseases (CVDs) were assessed. In total, 5672 NHL patients and 28 360 matched comparators were included. Time-varying incidence rate ratios (IRRs) showed increased risk of DM in the first year after treatment compared with matched comparators, with the highest IRR being 2.7. The absolute risks were higher among patients in the first 2 years, but the difference was clinically insignificant. NHL patients with preexisting DM had increased risks of insulin prescriptions with 0.5-, 5-, and 10-year cumulative risk differences of insulin treatment of 15.3, 11.8, and 6.0 percentage units as compared with the DM comparators. In a landmark analysis at 1 year, DM patients with lymphoma had decreased risks of insulin dependency compared with comparators. Time-varying IRRs showed a higher CVD risk for NHL patients with DM as compared with comparators in the first year after treatment. NHL patients treated with steroid-containing immunochemotherapy regimens have a clinically insignificant increased risk of DM in the first year following treatment, and patients with preexisting DM have a temporary increased risk of insulin prescriptions and CVD.
Developing and validating a mortality prediction model for ICH in ITP: a nationwide representative multicenter study
Authors: Chong Shan , Zhao Peng , Huang Rui-Bin , Zhou Hu , Zhang Jia-Ning , Hou Ming , Liu Yi , Yao Hong-Xia , Niu Ting , Peng Jun , Jiang Ming , Han Yan-Qiu , Hu Jian-Da , Zhou Ze-Ping , Qiu Lin , Zhang Lian-Sheng , Wang Xin , Wang Hua-Quan , Feng Ru , Yang Lin-Hua , Ma Liang-Ming , Wang Shun-Qing , Kong Pei-Yan , Wang Wen-Sheng , Sun Hui-Ping , Sun Jing , Zhou He-Bing , Zhu Tie-Nan , Wang Li-Ru , Zhang Jing-Yu , Huang Qiu-Sha , Fu Hai-Xia , Wu Ye-Jun , Li Yue-Ying , Wang Qian-Fei , Jiang Qian , Jiang Hao , Lu Jin , Huang Xiao-Jun , Zhang Xiao-Hui
Published: June 2022

Intracranial hemorrhage (ICH) is a rare and life-threatening hemorrhagic event in patients with immune thrombocytopenia (ITP). However, its mortality and related risk factors remain unclear. Herein, we conducted a nationwide multicenter real-world study of ICH in adult ITP patients. According to data from 27 centers in China from 2005 to 2020, the mortality rate from ICH was 33.80% (48/142) in ITP adults. We identified risk factors by logistic univariate and multivariate logistic regression for 30-day mortality in a training cohort of 107 patients as follows: intraparenchymal hemorrhage (IPH), platelet count ≤10 × 109/L at ICH, a combination of serious infections, grade of preceding bleeding events, and Glasgow coma scale (GCS) level on admission. Accordingly, a prognostic model of 30-day mortality was developed based on the regression equation. Then, we evaluated the performance of the prognostic model through a bootstrap procedure for internal validation. Furthermore, an external validation with data from a test cohort with 35 patients from 11 other centers was conducted. The areas under the receiver operating characteristic (ROC) curves for the internal and external validation were 0.954 (95% confidence interval [CI], 0.910-0.998) and 0.942 (95% CI, 0.871-1.014), respectively. Both calibration plots illustrated a high degree of consistency in the estimated and observed risk. In addition, the decision curve analysis showed a considerable net benefit for patients. Thus, an application (47.94.162.105:8080/ich/) was established for users to predict 30-day mortality when ICH occurred in adult patients with ITP.
CircVIS: a platform for circRNA visual presentation
Authors: Lin Ya-Chi , Wang Yun-Chin , Lee Yueh-Chun , Lin Hui-Hsuan , Chang Kai-Li , Tai Yu-Chieh , Hsiao Kuei-Yang
Published: June 2022

Background

The collection of circRNAs mostly focused on their sequence composition such as protein/miRNA binding motif, and/or regulatory elements such as internal ribosome entry site. However, less attention was paid to subcellular localization. CircVIS aimed to provide a collection of circRNAs with information of subcellular compartments and also integrated the circRNA entries from previous circRNA databases.

Results

A collection of circRNAs from public circRNA databases and de novo identification were annotated according to subcellular localizations including nucleoplasm, chromatin-associated parts, cytoplasm and polyribosome. All circRNAs were aligned to a selected major transcript, and if presence, the circRNA-derived open reading frame with annotation of functional domain were compared to its parental protein. The results showed that distinct circRNAs may exert their molecular and cellular functions in different subcellular compartments. The web service is made freely available at http://lab-x-omics.nchu.edu.tw/circVIS.

Conclusions

CircVIS allows users to visualize the alignment between a given circRNA and its most relevant reference transcript along with information of subcellular localization.
Changes in health-related lifestyles and food insecurity and its association with quality of life during the COVID-19 lockdown in Malaysia
Authors: Ahmad Aryati , Shahril Mohd Razif , Wan-Arfah Nadiah , Mohd Abu Bakar Wan Azdie , Piernas Carmen , Lua Pei Lin
Published: June 2022

Background

The pandemic of SARS CoV2 virus has severely impacted the entire world population. The lockdown imposed during the pandemic has created enormous challenges particularly on the health, economic and social life of most individuals. This study aimed to investigate the changes in health-related lifestyle and food security during the lockdown and how they influenced the quality of life (QoL) of Malaysian adults.

Methods

An online survey using a structured questionnaire consisting of sociodemographic, body weight, diet quality, physical activity, sleep quality, food insecurity, and QoL was conducted among adult respondents across Malaysia. Multivariate linear regression analyses were conducted to assess the associations between the changes in each component and QoL based on the total score before and during the lockdown.

Results

A total of 759 valid responses were included in the final analysis (75% female and 24.5% male). There was a significant improvement in diet quality during the lockdown while sleep quality and food insecurity worsened significantly. As for physical activity, metabolic equivalents (METs) in moderate activity increased significantly, whilst there was a significant decrease in the METs in walking and total minutes spent on physical activity during the lockdown. Overall, independent of age, gender, ethnicity, and religion, there were significant associations between QoL during lockdown and changes in BMI, METs of moderate activity, sleep quality, and food insecurity.

Conclusions

The unprecedented COVID-19 outbreak and the lockdown measure during the pandemic have caused significant negative changes in health-related lifestyles and affected the QoL of Malaysian adults. Despite the new norms and rules to prevent disease transmission, efforts to maintain a healthy lifestyle and food security among the population must be rolled out to improve the QoL and prevent further adverse mental and physical health outcomes.
The Public and Patient Engagement Evaluation Tool: forward-backwards translation and cultural adaption to Norwegian
Authors: Garratt Andrew , Sagen Joachim , Børøsund Elin , Varsi Cecilie , Kjeken Ingvild , Dagfinrud Hanne , Moe Rikke Helene
Published: June 2022

Background

Patient engagement is recommended for improving health care services, and to evaluate its organisation and impact appropriate, and rigorously evaluated outcome measures are needed.

Methods

Interviews (N = 12) were conducted to assess relevance of the Canadian Public and Patient Engagement Evaluation Tool (PPEET) in a Norwegian setting were performed. The tool was translated, back translated, and assessed following cognitive interviews (N = 13), according to the COSMIN checklist. Data quality was assessed in a cross-sectional survey of patient advisory board members from different rehabilitation institutions (N = 47).

Results

Interviews with patient board representatives confirmed the relevance of the PPEET Organisational questionnaire in a Norwegian setting and contributed five additional items. Translation and back translation of the original PPEET showed no major content differences. Differences in vocabulary and sentence structure were solved by discussion among the translators. Comments from cognitive interviews mainly related to the use of different synonyms, layout, and minor differences in semantic structure. Results of the cross-sectional survey support the data quality and construct validity of PPEET items, including 95 score comparisons where 76 (80%) were as hypothesized.

Conclusions

The PPEET Organisational questionnaire has been thoroughly translated and tested, and the resulting Evalueringsverktøy for Brukermedvirkning (EBNOR) has adequate levels of comprehensibility and content validity. Further testing for measurement properties is recommended, but given these results, the EBNOR should be considered for assessing patient engagement in a Norwegian health care organisational context.
Enhancer-promoter interaction maps provide insights into skeletal muscle-related traits in pig genome
Authors: Li Jingjin , Xiang Yue , Zhang Lu , Qi Xiaolong , Zheng Zhuqing , Zhou Peng , Tang Zhenshuang , Jin Yi , Zhao Qiulin , Fu Yuhua , Zhao Yunxia , Li Xinyun , Fu Liangliang , Zhao Shuhong
Published: June 2022

Background

Gene expression programs are intimately linked to the interplay of activecisregulatory elements mediated by chromatin contacts and associated RNAs. Genome-wide association studies (GWAS) have identified many variants in these regulatory elements that can contribute to phenotypic diversity. However, the functional interpretation of these variants remains nontrivial due to the lack of chromatin contact information or limited contact resolution. Furthermore, the distribution and role of chromatin-associated RNAs in gene expression and chromatin conformation remain poorly understood. To address this, we first present a comprehensive interaction map of nuclear dynamics of 3D chromatin-chromatin interactions (H3K27ac BL-HiChIP) and RNA-chromatin interactions (GRID-seq) to reveal genomic variants that contribute to complex skeletal muscle traits.

Results

In a genome-wide scan, we provide systematic fine mapping and gene prioritization from GWAS leading signals that underlie phenotypic variability of growth rate, meat quality, and carcass performance. A set of candidate functional variants and 54 target genes previously not detected were identified, with 71% of these candidate functional variants choosing to skip over their nearest gene to regulate the target gene in a long-range manner. The effects of three functional variants regulatingKLF6(related to days to 100 kg),MXRA8(related to lean meat percentage), andTAF11(related to loin muscle depth) were observed in two pig populations. Moreover, we find that this multi-omics interaction map consists of functional communities that are enriched in specific biological functions, and GWAS target genes can serve as core genes for exploring peripheral trait-relevant genes.

Conclusions

Our results provide a valuable resource of candidate functional variants for complex skeletal muscle-related traits and establish an integrated approach to complement existing 3D genomics by exploiting RNA-chromatin and chromatin-chromatin interactions for future association studies.
Perivascular macrophages in high-fat diet-induced hypothalamic inflammation
Authors: Mendes Natalia F. , Velloso Licio A.
Published: June 2022

Brain macrophages and microglia are centrally involved in immune surveillance of the central nervous system. Upon inflammatory stimuli, they become reactive and release key molecules to prevent further damage to the neuronal network. In the hypothalamic area, perivascular macrophages (PVMs) are the first line of host defence against pathogenic organisms, particles and/or substances from the blood. They are distributed throughout the circumventricular organ median eminence, wrapping endothelial cells from fenestrated portal capillaries and in the hypothalamic vascular network, where they are localised in the perivascular space of the blood–brain barrier (BBB). Some studies have indicated that PVMs from the hypothalamus increase the expression of inducible nitric oxide synthase and vascular endothelial growth factor upon feeding for a long time on a high-fat diet. This adaptive response contributes to the impairment of glucose uptake, facilitates BBB leakage and leads to increased lipid and inflammatory cell influx towards the hypothalamic parenchyma. Despite these early findings, there is still a lack of studies exploring the mechanisms by which PVMs contribute to the development of obesity-related hypothalamic dysfunction, particularly at the early stages when there is chemotaxis of peripheral myeloid cells into the mediobasal hypothalamus. Here, we reviewed the studies involving the ontogeny, hallmarks and main features of brain PVMs in vascular homeostasis, inflammation and neuroendocrine control. This review provides a framework for understanding the potential involvement of PVMs in diet-induced hypothalamic inflammation.
Advances in brain barriers and brain fluids research in 2021: great progress in a time of adversity
Authors: Keep Richard F. , Jones Hazel C. , Drewes Lester R.
Published: June 2022

This editorial highlights advances in brain barrier and brain fluid research in 2021. It covers research on components of the blood–brain barrier, neurovascular unit and brain fluid systems; how brain barriers and brain fluid systems are impacted by neurological disorders and their role in disease progression; and advances in strategies for treating such disorders.
Paclitaxel and cisplatin combined with concurrent involved-field irradiation in definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma: a phase II clinical trial
Authors: Li Hui , Fang Ying , Gu Dayong , Du Mingyu , Zhang Zhi , Sun Lei , Zhou Guoren , Ye Jinjun
Published: June 2022

Purpose

This trial aims to explore the efficacy and safety of involved-field irradiation (IFI) combined with paclitaxel plus cisplatin as concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma (ESCC), under the premise of intensity-modulated radiotherapy (IMRT).

Methods

Enrolled patients with locally advanced ESCC were treated with definitive concurrent chemoradiotherapy. IFI was administered adopting IMRT and the total dose was 61.2 Gy delivered in 34 fractions. On the first day of radiotherapy, the patients were treated with paclitaxel and cisplatin one cycle per month for 2 cycles followed by the same regimen in consolidation chemotherapy for two cycles. The primary endpoint of the study was the 2-year locoregional recurrence-free survival (LRFS) rate, and secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety.

Results

Between January 2018 and September 2020, 108 patients participated in the trial. 78.7% (85/108) of patients completed all 4 cycles of chemotherapy. The median follow-up of the surviving patients was 33.9 months (interquartile range, 29.2–41.1). The 2-year LRFS rate, as the primary endpoint, was 64.2%. In addition, the median PFS was 39.2 months, and 1-year and 3-year OS rates of 88.0% and 63.3%, respectively. Among the patients, out-of-field regional failure was seen in only 7 (6.5%) patients. Neutropenia grade 3 and 4 occurred in 21.3% and 37.0% of the patients, respectively.

Conclusions

IFI using IMRT combined with paclitaxel and cisplatin concurrent chemotherapy for locally advanced ESCC yields encouraging local control and overall survival, but high hematological toxicity.

Trial registration Clinical Trials ChiCTR1800017039.
Surgical treatment of papillary fibroelastoma of the pulmonary valve: a case report
Authors: Uehara Hiroo , Uchiyama Masateru , Hori Takayuki , Iida Mitsuru , Imazuru Tomohiro , Shimokawa Tomoki
Published: June 2022

Background

Cardiac papillary fibroelastoma (PFE) is a rare tumor, and especially rare when found on the pulmonary valve.

Case presentation

We report the case of a 70-year-old woman patient with a pulmonary valve PFE diagnosed incidentally during a follow-up of aortic regurgitation. Computed tomography and magnetic resonance imaging showed no suggestive signs of malignant tumors, and thrombus or myxoma was initially suspected. However, an initial transthoracic and transesophageal echocardiogram did not exclude the possibility of a malignant tumor attached to the wall of the pulmonary artery. Considering the embolization risk, we opted to perform tumorectomy, in which additional surgical procedures could then be conducted if intraoperative diagnosis showed a malignant tumor. Indeed, intraoperative findings showed the tumoral mass attached on the left semilunar cusp of the pulmonary valve, and intraoperative diagnosis of the tumor showed no malignancy. Planned tumorectomy was performed concomitantly with AVR. The pathologic examination of the removed tumor confirmed the diagnosis of PFE. Her postoperative course was uneventful without any sign of recurrence.

Conclusion

This case highlights the difficulty of accurate diagnostic imaging and provides valuable insight into a successful surgical treatment of pulmonary valve PFE without any complications.
Early versus delayed enteral nutrition in mechanically ventilated patients with circulatory shock: a nested cohort analysis of an international multicenter, pragmatic clinical trial
Authors: Ortiz-Reyes Luis , Patel Jayshil J. , Jiang Xuran , Coz Yataco Angel , Day Andrew G. , Shah Faraaz , Zelten James , Tamae-Kakazu Maximiliano , Rice Todd , Heyland Daren K.
Published: June 2022

Introduction

Real-world evidence on the timing and efficacy of enteral nutrition (EN) practices in intensive care unit (ICU) patients with circulatory shock is limited. We hypothesized early EN (EEN), as compared to delayed EN (DEN), is associated with improved clinical outcomes in mechanically ventilated (MV) patients with circulatory shock.

Methods

We analyzed a dataset from an international, multicenter, pragmatic randomized clinical trial (RCT) evaluating protein dose in ICU patients. Data were collected from ICU admission, and EEN was defined as initiating < 48 h from ICU admission and DEN > 48 h. We identified MV patients in circulatory shock to evaluate the association between the timing of EN initiation and clinical outcomes. The regression analysis model controlled for age, mNUTRIC score, APACHE II score, sepsis, and Site.

Results

We included 626 patients, from 52 ICUs in 14 countries. Median age was 60 years [18–93], 55% had septic shock, 99% received norepinephrine alone, 91% received EN alone, and 50.3% were randomized to a usual protein dose. Forty-two percent of EEN patients had persistent organ dysfunction syndrome plus death at day 28, compared to 53% in the DEN group (p = 0.04). EEN was associated with more ICU-free days (9.3 ± 9.2 vs. 5.7 ± 7.9, p = 0.0002), more days alive and free of vasopressors (7.1 ± 3.1 vs. 6.3 ± 3.2, p = 0.007), and shorter duration of MV among survivors (9.8 ± 10.9 vs. 13.8 ± 14.5, p = 0.0002). This trend was no longer observed in the adjusted analysis. There were no differences in ICU/60-day mortality or feeding intolerance rates between groups.

Conclusion

In MV patients with circulatory shock, EEN, as compared to DEN, was associated with improved clinical outcomes, but no longer when adjusting for illness severity. RCTs comparing the efficacy of EEN to DEN in MV patients with circulatory shock are warranted.
3D printed models in pregnancy and its utility in improving psychological constructs: a case series
Authors: Coté John Joseph , Coté Brayden Patric , Badura-Brack Amy S.
Published: June 2022

Background

3D printing is being utilized in almost every aspect of medicine. 3D printing has especially been used in conjunction with 3D ultrasonography to assist in antenatal assessment and presurgical planning with fetal malformations. As printing capabilities improve and applications are explored there may be more advantages for all parents to visualize and touch 3D printed models of their fetus.

Case presentation

We present three cases involving 3D printed models and four different but interrelated psychological constructs- antenatal depression, antenatal anxiety, maternal-fetal attachment, and paternal-fetal attachment. Each case shows for the first time possible beneficial effects within these prevalent and significant problems.

Conclusions

The degree to which the anxiety, depression, and attachment scores improved after the presentation of the 3D printed models is encouraging. Randomized controlled trials utilizing 3D printed models to improve psychological constructs should be supported considering the findings within these four cases.
Computer-assisted tumor grading, validation of PD-L1 scoring, and quantification of CD8-positive immune cell density in urothelial carcinoma, a visual guide for pathologists using QuPath
Authors: Rodrigues Aline , Nogueira Cleto , Marinho Laura Cardoso , Velozo Guilherme , Sousa Juliana , Silva Paulo Goberlanio , Tavora Fabio
Published: June 2022

Background

Advances in digital imaging in pathology and the new capacity to scan high-quality images have change the way to practice and research in surgical pathology. QuPath is an open-source pathology software that offers a reproducible way to analyze quantified variables. We aimed to present the functionality of biomarker scoring using QuPath and provide a guide for the validation of pathologic grading using a series of cases of urothelial carcinomas.

Methods

Tissue microarrays of urothelial carcinomas were constructed and scanned. The images stained with HE, CD8 and PD-L1 immunohistochemistry were imported into QuPath and dearrayed. Training images were used to build a grade classifier and applied to all cases. Quantification of CD8 and PD-L1 was undertaken for each core using cytoplasmic and membrane color segmentation and output measurement and compared with pathologists semi-quantitative assessments.

Results

There was a good correlation between tumor grade by the pathologist and by QuPath software (Kappa agreement 0.73). For low-grade carcinomas (by the report and pathologist), the concordance was not as high. Of the 32 low-grade tumors, 22 were correctly classified as low-grade, but 11 (34%) were diagnosed as high-grade, with the high-grade to the low-grade ratio in these misclassified cases ranging from 0.41 to 0.58. The median ratio for bona fide high-grade carcinomas was 0.59. Some of the reasons the authors list as potential mimickers for high-grade cases are fulguration artifact, nuclear hyperchromasia, folded tissues, and inconsistency in staining. The correlation analysis between the software and the pathologist showed that the CD8 marker showed a moderate (r = 0.595) and statistically significant (p < 0.001) correlation. The internal consistency of this parameter showed an index of 0.470. The correlation analysis between the software and the pathologist showed that the PDL1 marker showed a robust (r = 0.834) and significant (p < 0.001) correlation. The internal consistency of this parameter showed a CCI of 0.851.

Conclusions

We were able to demonstrate the utility of QuPath in identifying and scoring tumor cells and IHC quantification of two biomarkers. The protocol we present uses a free open-source platform to help researchers deal with imaging and data processing in the surgical pathology field.
Sexual abuse and mental ill health in boys and men: what we do and don't know
Authors: Rice Simon M. , Easton Scott D. , Seidler Zac E. , Oliffe John L.
Published: June 2022

The spectrum of adverse mental health trajectories caused by sexual abuse, broadly defined as exposure to rape and unwanted physical sexual contact, is well-known. Few studies have systematically appraised the epidemiology and impact of sexual abuse among boys and men. New meta-analytic insights (k = 44; n = 45 172) reported by Zarchev and colleagues challenge assumptions that men experiencing mental ill health rarely report sexual abuse exposure. Adult-onset sexual abuse rates of 1–7% are observed in the general population, but for men experiencing mental ill health, adult lifetime prevalence was 14.1% (95% CI 7.3–22.4%), with past-year exposure 5.3% (95% CI 1.6–12.8%). We note that these rates are certainly underestimates, as childhood sexual abuse exposures were excluded. Boys and men with a sexual abuse history experience substantial disclosure and treatment barriers. We draw attention to population health gains that could be achieved via implementation of gender-sensitive assessment and intervention approaches for this at-risk population.
Alzheimer Disease
Authors: McDade Eric M.
Published: June 2022

PURPOSE OF REVIEW

Alzheimer disease (AD) is the most common cause of dementia in adults (mid to late life), highlighting the importance of understanding the risk factors, clinical manifestations, and recent developments in diagnostic testing and therapeutics.

RECENT FINDINGS

Advances in fluid (CSF and blood-based) and imaging biomarkers are allowing for a more precise and earlier diagnosis of AD (relative to non-AD dementias) across the disease spectrum and in patients with atypical clinical features. Specifically, tau- and amyloid-related AD pathologic changes can now be measured by CSF, plasma, and positron emission tomography (PET) with good precision. Additionally, a better understanding of risk factors for AD has highlighted the need for clinicians to address comorbidities to maximize prevention of cognitive decline in those at risk or to slow decline in patients who are symptomatic. Recent clinical trials of amyloid-lowering drugs have provided not only some optimism that amyloid reduction or prevention may be beneficial but also a recognition that addressing additional targets will be necessary for significant disease modification.

Recent developments in fluid and imaging biomarkers have led to the improved understanding of AD as a chronic condition with a protracted presymptomatic phase followed by the clinical stage traditionally recognized by neurologists. As clinical trials of potential disease-modifying therapies continue, important developments in the understanding of the disease will improve clinical care now and lead to more effective therapies in the near future.
An Intimate “Range of Elsewhere”: Sensuous Imaginaries of the Indian Ocean in Precolonial Swahili Poetry
Authors: Vierke Clarissa
Published: June 2022

The Swahili poetry of the master poet Fumo Liyongo, which dates between the fifteenth and eighteenth centuries, draws much of its imagery from the Indian Ocean, and in a particularly sensuous way: the poems paint baroque tableaux of Swahili material culture, evoking multiple elsewheres. They conjure the Indian Ocean through tastes, scents, and views of its rich interiors, which delineate a distinctively coastal world implicated to different degrees in the vaster oceanic region. Borrowing from aesthetic theories, the article explores the poem’s sensuality as a productive way of “thinking” about Indian Ocean relations, namely as a continual reemergence of cycles of sensation, questioning the clear-cut dichotomy of the “exterior” world and “intimate” notions of irreducible personhood as well as notions of local and cosmopolitan. Zeroing in on the betel quid, which has turned into a “mythological” cultural node of Swahili identity as well as a prominent rhetorical topos of Swahili love poetry, this article explores its imaginative productivity.
Asia Rising Is an Imperial Fiction: A View from the Indian Ocean
Authors: Qadir Neelofer
Published: June 2022

Popular rhetoric of the twenty-first century as the “Asian century” frequently coheres around China as a rising global superpower and thus focuses on its financial and material ambitions in sites across Asia and Africa. Such narratives, ensconced within the BRICS (Brazil, Russia, India, China, and South Africa) formation, re-entrench a problematic Orientalism while pushing further to the margins still the complex, long-standing regional histories. This essay juxtaposes Amitav Ghosh’s Ibis trilogy and Kevin Kwan’s Rich trilogy in relation to Indian Ocean histories of trade and exchange. Through world-historical events activated in these novels such as World War II and the first Anglo-Opium War, the essay’s argument follows nineteenth- and twentieth-century transits between the South Asian subcontinent, the Malay Archipelago, and China. Taking circularity as a central analytic, this essay reveals how an elongated temporal frame that accounts from non-European vantages—even in contemporary Anglophone literature—reorients not only what we consider the past and present of Indian Ocean worlds, but also how those pasts bear on the contemporary.