bluuebunny/crossref_metadata_2025 huggingface dataset:
O novo Ensino Médio no contexto brasileiro: Perspectivas e Reflexões do desempenho escolar nas disciplinas de Português e Matemática
Authors: Silva Diane Elias Rocha e , Jacob Merian Souza da Penha , Gomes Rodrigo da Vitória , Silva Josélia Cristina Siqueira da
Published: May 2021

A procura pela melhoria na qualidade do ensino é percorrida por vários caminhos, e são através destes que realizamos levantamentos, estudos, questionamentos de circunstâncias e análises dos fatores que afetam o desempenho escolar. O presente estudo tem como objetivo fazer um levantamento acerca da importância do ensino médio nas escolas, bem como problematizar a crise enfrentada nos dias atuais em relação ao desempenho escolar, e o grande desafio de aprendizado em relação às disciplinas de português e matemática no ensino médio, levando em consideração dados e estatísticas sobre a importância de tais conteúdos na formação escolar. A metodologia abordada nessa pesquisa apresenta natureza qualitativa dentro de uma perspectiva bibliográfica exploratória. Os resultados identificam que as dificuldades apresentadas pelos alunos de ensino médio, prejudicam e atrapalham o desenvolvimento dos mesmos no decorrer da formação escolar e também gera um resultado negativo no desenvolvimento social e econômico do Brasil. A partir destes resultados, discute-se a importância dos agentes que podem modificar essa atual realidade vivenciada no cenário brasileiro.
The development of Spiritual Nursing Care Theory using deductive axiomatic approach
Authors: Bangcola Ashley A.
Published: May 2021

The concepts of spirituality and spiritual well-being are not novel ideas as they have been subjects of scrutiny in several studies. However, there has yet to be a formalized framework of spiritual nursing in the Philippines despite its importance. Developing such a framework is significant, especially since holistic nursing believes in the relationships among body, mind, and spirit. Thus, the Spiritual Nursing Care theory was conceptualized, which states that every person has holistic needs, including spiritual needs that must be satisfied to attain spiritual well-being. It forwards that for the patient’s spiritual needs to be met, what is required is the triumvirate interconnection among the nurse, the external environment, and the spiritual nursing care which may be provided by the nurse as a healthcare provider and the significant others or family as part of the external environment. The theory has two propositions that were subjected to validation studies that either strengthened or repudiated the propositions presented: (1) the meaning of spirituality differs from person to person, and (2) the patient’s spiritual well-being is influenced by the nurse’s spiritual care competence, as well as the patient’s internal and external variables.
Studi Kasus Asuhan Kebidanan pada Ibu Bersalin dengan Preeklampsi Berat di RSUD Ciamis
Authors: Heryani Heni
Published: May 2021

One of the main causes of maternal mortality is severe preeclampsia. Severe absorption is an increase in blood pressure and proteinuria that occurs after 20 weeks of gestation. If severe preeclampsia is not treated quickly and precisely, it can turn into eclampsia. The purpose of this study was to provide an overview of the midwifery care of maternity women with severe preeclampsia at Ciamis Regional Hospital. The research method used was descriptive qualitative with a case study approach. The subjects in this study were Mrs. E, 32 years old with severe preeclampsia. This research was conducted from 5 to 6 March 2020 at Ciamis Hospital. The results of research on Mrs. E age 32 years G2P1A0 37 weeks of active phase 1 labor with severe preeclampsia of live single fetus. Handling carried out on Mrs. E has been carried out in accordance with the care plan that has been made. Midwives carry out midwifery care in accordance with midwifery care standards starting from assessment, formulation of midwifery diagnoses or problems, planning, implementation and evaluation.

Keywords: maternity; severe preeclampsia

ABSTRAK

Salah satu penyebab utama dari angka kematian ibu adalah preeklamsia berat. Preeklampsia berat adalah peningkatan tekanan darah dan proteinuria yang terjadi setelah usia kehamilan 20 minggu. Jika preeklampsi berat tidak segera ditangani dengan cepat dan tepat maka hal ini dapat berubah menjadi eklampsia. Tujuan Penelitian ini adalah untuk memberikan gambaran tentang Asuhan Kebidanan pada Ibu Bersalin dengan Preeklampsia Berat di RSUD Ciamis. Metode penelitian yang digunakan adalah deskriptif kualitatif dengan pendekatan studi kasus. Subjek dalam penelitian ini adalah Ny. E umur 32 tahun dengan Preeklampsia Berat (PEB). Penelitian ini dilakukan mulai tanggal 5 sampai dengan 6 maret 2020 yang bertempat di RSUD Ciamis. Hasil penelitian pada Ny. E umur 32 tahun G2P1A0 37 minggu persalinan kala 1 fase aktif dengan Preeklampsia Berat (PEB) janin tunggal hidup, Penanganan yang dilakukan pada Ny. E telah dilakukan sesuai dengan rencana asuhan yang telah dibuat. Bidan melakukan asuhan kebidanan sesuai dengan standar asuhan kebidanan mulai dari pengkajian, perumusan diagnosa atau masalah kebidanan, perencanaan, implementasi dan evaluasi.

Kata kunci: ibu bersalin; preeklamsia berat
Diabetes Mellitus dengan Status Gizi (Underweight) dalam Meningkatkan Resiko Kasus Tuberkulosis : Studi Kasus Kontrol di Puskesmas Mulyorejo
Authors: Marbun Romaden , Widi Wisoedhanie , Dea Vincensia
Published: May 2021

The incidence and prevalence of tuberculosis (TB) and Diabetes Mellitus (DM) now is increasing rapidly in the world. The International Diabetes Federation reports that people with Diabetes Mellitus have a higher risk of developing tuberculosis. There are several risk factors that are thought to increase the incidence of tuberculosis, one of which is Diabetes Mellitus (DM). This study aims to determine the relations between DM and the incidence of TB at Puskesmas Mulyorejo Malang. The research design was case control. The sample consisted of 114 respondents covering 57 for the control group and 57 for the case group. Data analysis using logistic regression. In the tuberculosis group, the percentage of respondents with DM was 64.9%, while in the group who did not suffer from tuberculosis, the percentage of respondents with DM was 24.6%. In this study, DM interacted with nutritional status (underweight). Means, at the same smoking habit, the relationship between DM and TB incidence is different according to the nutritional status of the respondent. For the underweight respondents, DM has a 20.0 times higher chance of developing TB than respondents who do not have diabetes. For the future, the researchers who will conduct similar research can discusse more and also improve this research with broader research variables in form of correlation. Diabetes mellitus is a disease that can cause a decrease in the cellular immune system.

Keywords: diabetes mellitus; tuberculosis

ABSTRAK

Insidensi dan prevalensi penyakit tuberkulosis (TB) dan Diabetes Mellitus (DM) meningkat cepat di dunia. International Diabetes Federation melaporkan penderita Diabetes Mellitus berisiko lebih tinggi untuk berkembang menjadi tuberkulosis. Terdapat beberapa faktor resiko yang diduga dapat meningkatkan kejadian Tuberkulosis, salah satunya adalah Diabetes Mellitus (DM) Penelitian ini bertujuan untuk mengetahui Hubungan antara DM dengan kejadian TB di Puskesmas Mulyorejo Malang. Desain penelitian adalah case control. Sampel berjumlah 114 responden yang meliputi 57 untuk kelompok kontrol dan 57 untuk kelompok kasus. Analisis Data menggunakan regresi logistik. Pada kelompok tuberkulsosis, presentase responden dengan DM sebesar 64,9%, sedangkan pada kelompok yang tidak menderita tuberkulosis, persentase responden dengan DM sebesar 24,6%. Pada penelitian ini, DM berinteraksi dengan status gizi (underweight). Artinya, pada kebiasaan merokok yang sama, hubungan DM dengan kejadian TB berbeda menurut status gizi responden. Pada responden yang underweight, DM memiliki peluang 20,0 kali lebih tinggi untuk terjadi TB dibandingkan responden yang tidak DM. Diabetes mellitus merupakan suatu penyakit yang dapat menyebabkan penurunan sistem imunitas selular.

Kata kunci: diabetes melitus; tuberkulosis
Studi Kasus : Manajemen Asuhan Kebidanan Pada Ibu Bersalin Dengan Persalinan Prematur di RSUD Ciamis
Authors: Lestari Lusi
Published: May 2021

Premature labor or premature contractions are the main causes of perinatal death and one of the most common causes of disability in children due to poor neurodevelopment. Preterm labor is a dangerous thing because it has the potential to increase perinatal mortality by 65% -75%. The purpose of this study was to provide an overview of the midwifery care of maternity women with premature contractions at Ciamis Regional Hospital. The research method used in this research was a descriptive qualitative method with an individual case study approach. The subjects in this study were Mrs. Y Age 26 Years G2P1A0 with Premature Contractions. The research was conducted in a day on March 5, 2020, at Ciamis Hospital. The results showed an intervention was made in accordance with the midwifery care plan is based on the theory and client needs. Midwives in providing care in accordance with the authority of the midwife. The evaluation results obtained that Mrs. Y had no complaints, TTV was within normal limits.

Keywords: midwifery care; premature contractions

ABSTRAK

Persalinan prematur atau prematur kontraksi adalah penyebab utama kematian perinatal dan merupakan salah satu penyebab terbanyak kecacatan pada anak akibat perkembangan saraf yang tidak baik. Persalinan prematur merupakan hal yang berbahaya karena potensial meningkatkan kematian perinatal sebesar 65%-75%. Tujuan penelitian ini adalah untuk memberikan gambaran tentang Asuhan Kebidanan pada Ibu Bersalin dengan Prematur Kontraksi di RSUD Ciamis. Metode penelitian yang digunakan dalam penelitian ini adalah metode deskriptif kualitatif dengan pendekatan studi kasus pada individu. Subjek dalam penelitian ini adalah Ny. Y umur 26 Tahun G2P1A0 dengan Prematur Kontraksi. Waktu pelaksanaan penelitian selama 1 hari pada tanggal 5 Maret 2020 di RSUD Ciamis. Hasil penelitian menunjukkan penanganan dilakukan sesuai dengan rencana asuhan kebidanan yang dibuat berdasarkan teori dan kebutuhan klien. Bidan dalam memberikan asuhan sesuai dengan kewenangan bidan. Hasil evaluasi diperoleh Ny.Y sudah tidak ada keluhan, TTV dalam batas normal.

Kata kunci: asuhan kebidanan; prematur kontraksi
Literature Review : Evaluasi Peer Group Support dan Family Support Terhadap Kepatuhan Pengobatan Pada Pasien Tuberkulosis Paru
Authors: Suarnianti Suarnianti , Selan Chairul Hasan , Sumi Susi Sastika
Published: May 2021

Tuberculosis (TB) is an infectious disease which is the leading cause of ill health, one of the top 10 causes of death worldwide and the leading cause of death from a single infectious agent (ranking above HIV / AIDS). WHO estimates that there are 23,000 cases of MDR / RR in Indonesia. In 2017 there were 442,000 TB cases recorded in the program, of which an estimated 8,600-15,000 MDR / RR TB, (estimated 2.4% of new cases and 13% of previously treated TB patients), but only 27.36% treated. The aim of this literature is to evaluate peer group support and family support on treatment adherence to pulmonary tuberculosis patients. This study used a systematic literature review design. Articles were collected through the PubMed and Google Scholar databases published from 2016-2020 using the keywords peer group support, family support, medication adherence, pulmonary tuberculosis. The results of the literature review showed that providing peer group support or family support can have an impact positive for pulmonary tuberculosis patients. The conclusion in this study is that patients who get support from either peer group support or family support can significantly improve compliance with pulmonary tuberculosis treatment so that it can increase the success rate of pulmonary tuberculosis treatment.

Keywords: peer group support; family support; treatment compliance; pulmonary tuberculosis

ABSTRAK

Tuberkulosis (TB) adalah penyakit menular yang merupakan penyebab utama masalah kesehatan yang buruk, salah satu dari 10 penyebab utama kematian di seluruh dunia dan penyebab utama kematian dari satu agen infeksi tunggal (peringkat di atas HIV / AIDS). WHO memperkirakan ada 23.000 kasus MDR/RR di Indonesia. Pada tahun 2017 kasus TB yang tercatat di program ada sejumlah 442.000 kasus yang mana dari kasus tersebut diperkirakan ada 8.600-15.000 MDR/RR TB, (perkiraan 2,4% dari kasus baru dan 13% dari pasien TB yang diobati sebelumnya), tetapi cakupan yang diobati baru sekitar 27,36%. Tujuan Literatur ini untuk mengevaluasi peer group support dan family support terhadap kepatuhan pengobatan pasien tuberkulosis paru. Penelitian ini menggunakan desain systematic literature review. Artikel dikumpulkan melalui database PubMed dan Google Scholar yang dipublikasikan dari tahun 2016-2020 dengan menggunakan kata kunci peer group support, family support, kepatuhan pengobatan, tuberkulosis paru. Hasil literature review menunjukkan bahwa pemberian peer group support atau family support dapat memberikan dampak yang positif kepada pasien tuberkulosis paru. Kesimpulan dalam penelitian ini bahwa pasien yang mendapatkan dukungan baik peer group support atau family support secara signifikan dapat meningkatkan kepatuhan pengobatan tuberkulosis paru sehingga dapat meningkatkan tingkat keberhasilan pengobatan tuberkulosis paru

Kata kunci: peer group support; family support; kepatuhan pengobatan; tuberkulosis paru
Perbedaan Sonopattern Ultrasonografi Kandung Empedu pada Kasus Cholelithiasis & Galbladder Polyp
Authors: Fiddinillah Fiddinillah , Sriyatun Sriyatun , Nurbaiti Nurbaiti , Apriantoro Nursama Heru
Published: May 2021

On ultrasound examination of the gallbladder Cholelithiasis and Gallbladder Polyp usually have similar results but have their own characteristics that can differentiate. In the image results Cholelithiasis, which is usually called gallstones, has a characteristic Sonopattern Hyperechoic with an Acousstic Shadow behind it, where when using the technique the patient's position changes the stone according to the direction of Earth's gravity. While the results of the Gallbladder Polyp image, which is a tumor protrusion attached to the gallbladder wall, has the characteristic Sonopattern Hyperecoic without an acoustic shadow behind it, where when using the technique the patient's position changes not according to the direction of Earth's gravity. In both cases, the presence or absence of an acoustic shadow behind it is based on the density of the tissue that the sound waves pass through from the ultrasound device, so that when passing through the stone, the acoustic shadow is more visible than when passing through the tumor tissue..

Keywords: sonopattern ultrasound; cholelithiasis; gallbladder polyp

ABSTRAK

Pada pemeriksaan USG kandung empedu Cholelithiasis dan Gallbladder Polyp biasanya memiliki hasil gambaran yang serupa tetapi memiliki ciri khasnya masing-masing yang dapat membedakan. Pada hasil gambaran Cholelithiasis yang biasa disebut batu empedu memiliki ciri khas Sonopattern Hyperechoic dengan Acousstic Shadow di belakangnya, ketika menggunakan teknik dengan posisi pasien yang berubah batu mengikuti arah gravitasi bumi. Sementara pada hasil gambaran Gallbladder Polyp yang merupakan tonjolan tumor yang menempel pada dinding kandung empedu memiliki ciri khas Sonopattern Hyperecoic tanpa Accoustic Shadow dibelakangnya, dimana ketika menggunakan teknik dengan posisi pasien yang berubah tidak mengikuti arah gravitasi bumi. Pada kedua kasus ini ada tidaknya Accoustic Shadow di belakangnya didasari oleh kepadatan jaringan yang dilalui oleh gelombang suara dari alat USG, sehingga saat melewati batu lebih tampak Accoustic Shadow dibandingkan saat melewati jaringan tumor.

Kata kunci: sonopattern ultrasound; cholelithiasis; gallbladder polyp
Phenotypic Trait Variation in Populations of a Global Invader Mayweed Chamomile (Anthemis cotula): Implications for Weed Management
Authors: Adhikari Subodh , Burke Ian C. , Piaskowski Julia , Eigenbrode Sanford D.
Published: May 2021

Mayweed chamomile (Anthemis cotula L.) is an annual crop weed that has become a substantial impediment to diversify traditional wheat-based cropping systems such as in the Pacific Northwest (PNW), USA. Some of the broadleaf rotational crops are vulnerable to the weed as they are less competitive or lack compatible herbicides for A. cotula management. Although A. cotula has been present in the PNW for more than a century, traits that contribute to invasiveness and how these vary among the weed populations have not been investigated. We assessed trait variation with a common garden greenhouse experiment by comparing 19 A. cotula populations from the PNW and Kashmir Valley, India. Seeds from individual plants from each population were used to grow plants through their senescence. We measured phenological (e.g., flowering duration), morphological (e.g., plant biomass), reproductive fitness (e.g., number of flower heads), and physiological (floral scent VOCs: volatile organic compounds) traits on individual plants and analyzed the data using mixed-effects models. We found high inter-population variation in most of the traits measured, but the variation was not associated with the geographical distance. Seedling emergence within 30 days of planting ranged from 2 to 49% for PNW populations to 55 to 72% for Indian populations. Flowering duration ranged from 2 to 3 months among populations. Other traits such as initial and final flowering dates, the total number of flower heads, and floral scent VOCs also differed among populations. These trait patterns may indicate a localized adaptation of A. cotula populations to environmental or management regimes, variation arising from anthropogenic or natural dispersal, multiple introductions, genetic drift, or combinations of these. Regardless of the processes, the trait variation suggests that weed management plan for A. cotula may need to be tailored to specific locations instead of a uniformly adopted plan across the region.
Performance Analysis of Trust Region Subproblem Solvers for Limited-Memory Distributed BFGS Optimization Method
Authors: Gao Guohua , Florez Horacio , Vink Jeroen C. , Wells Terence J. , Saaf Fredrik , Blom Carl P. A.
Published: May 2021

The limited-memory Broyden–Fletcher–Goldfarb–Shanno (L-BFGS) optimization method performs very efficiently for large-scale problems. A trust region search method generally performs more efficiently and robustly than a line search method, especially when the gradient of the objective function cannot be accurately evaluated. The computational cost of an L-BFGS trust region subproblem (TRS) solver depend mainly on the number of unknown variables (n) and the number of variable shift vectors and gradient change vectors (m) used for Hessian updating, withm << nfor large-scale problems. In this paper, we analyze the performances of different methods to solve the L-BFGS TRS. The first method is the direct method using the Newton-Raphson (DNR) method and Cholesky factorization of a densen×nmatrix, the second one is the direct method based on an inverse quadratic (DIQ) interpolation, and the third one is a new method that combines the matrix inversion lemma (MIL) with an approach to update associated matrices and vectors. The MIL approach is applied to reduce the dimension of the original problem withnvariables to a new problem withmvariables. Instead of directly using expensive matrix-matrix and matrix-vector multiplications to solve the L-BFGS TRS, a more efficient approach is employed to update matrices and vectors iteratively. The L-BFGS TRS solver using the MIL method performs more efficiently than using the DNR method or DIQ method. Testing on a representative suite of problems indicates that the new method can converge to optimal solutions comparable to those obtained using the DNR or DIQ method. Its computational cost represents only a modest overhead over the well-known L-BFGS line-search method but delivers improved stability in the presence of inaccurate gradients. When compared to the solver using the DNR or DIQ method, the new TRS solver can reduce computational cost by a factor proportional ton2/mfor large-scale problems.
Small Intestinal Bacterial Overgrowth in Subclinical Hypothyroidism of Pregnant Women
Authors: Wang Biao , Xu Yajuan , Hou Xiaofeng , Li Jingjing , Cai Yanjun , Hao Yingqi , Ouyang Qian , Wu Bo , Sun Zongzong , Zhang Miao , Ban Yanjie
Published: May 2021

Objective

To evaluate the small intestinal bacterial overgrowth (SIBO) of subclinical hypothyroidism of pregnant women, and explore their possible relevance.

Methods

In total, 224 pregnant women with subclinical hypothyroidism during pregnancy (study group) and 196 pregnant women whose thyroid function was normal (control group) were enrolled in this study. Lactulose-based hydrogen and methane breath test was performed to evaluate the growth of intestinal bacteria. The serum-free thyroid hormone (FT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), body mass index (BMI) and gastrointestinal symptoms were detected and recorded.

Results

The positive rates of SIBO were 56.7% and 31.6% in study group and control group, respectively. The levels of C response protein (CRP), abdominal distension and constipation in study group were higher than those in the control group. The risk of abdominal distension and constipation in SIBO-positive pregnant women were higher than that in SIBO-negative pregnant women, and the BMI of SIBO-positive patients in the two groups was lower than that of SIBO-negative patients in each group. In addition, the TPOAb-positive rate and TSH levels were higher but the FT4 level was lower in SIBO-positive patients compared to SIBO-negative patients in study group.

Conclusion

The occurrence of subclinical hypothyroidism is related to SIBO, and the excessive growth of small intestinal bacteria may affect gastrointestinal symptoms.

Clinical Trial

http://www.chictr.org.cn/index.aspx, identifier ChiCTR1900026326.
Effects of Sorafenib, a Tyrosin Kinase Inhibitor, on Adrenocortical Cancer
Authors: Cerquetti Lidia , Bucci Barbara , Raffa Salvatore , Amendola Donatella , Maggio Roberta , Lardo Pina , Petrangeli Elisa , Torrisi Maria Rosaria , Toscano Vincenzo , Pugliese Giuseppe , Stigliano Antonio
Published: May 2021

The lack of an effective medical treatment for adrenocortical carcinoma (ACC) has prompted the search for better treatment protocols for ACC neoplasms. Sorafenib, a tyrosine kinase inhibitor has exhibited effectiveness in the treatment of different human tumors. Therefore, the aim of this study was to understand the mechanism through which sorafenib acts on ACC, especially since treatment with sorafenib alone is sometimes unable to induce a long-lasting antiproliferative effect in this tumor type. The effects of sorafenib were tested on the ACC cell line H295R by evaluating cell viability, apoptosis and VEGF receptor signaling which was assessed by analyzing VE-cadherin and β-catenin complex formation. We also tested sorafenib on an in vitro 3D cell culture model using the same cell line. Apoptosis was observed after sorafenib treatment, and coimmunoprecipitation data suggested that the drug prevents formation VEGFR-VE-cadherin and β-catenin proteins complex. These results were confirmed both by ultrastructural analysis and by a 3D model where we observed a disaggregation of spheres into single cells, which is a crucial event that represents the first step of metastasis. Our findings suggest that although sorafenib induces apoptotic cell death a small portion of cells survive the treatment and have characteristics of a malignancy. Based on our data we recommend against the use of sorafenib in patients with ACC.
Adults’ Adherence to Growth Hormone Replacement in Relation to Medication-Related Beliefs, Coping and Quality of Life - An Exploratory Analysis
Authors: Siegel Sonja , Unger Nicole , Streetz-van der Werf Christine , Karges Wolfram , Schilbach Katharina , Schröder Bernadette , Szybowicz Janine , Sauerwald Janina , Zopf Kathrin , Grzywotz Agnieszka , Bidlingmaier Martin , Kirstein Cedric , Sommer Heide , Strasburger Christian J. , Kreitschmann-Andermahr Ilonka
Published: May 2021

Introduction

Little is known about psychological reasons associated with adherence to growth hormone (GH) replacement therapy (GHRx) in adults. As in other chronic diseases, medication-related beliefs, coping strategies and disease impact on quality of life (QoL) might play an important role. We thus explored these psychological factors in relation to adherence in patients with GH deficiency (GHD) in order to find leverage points for the improvement of adherence.

Patients and Methods

Cross-sectional analysis including 107 adult GHD patients on GHRx who completed self-assessment inventories on health-related QoL (Short-Form SF-36), coping style (Freiburg questionnaire on coping with illness, FKV-LIS) and medication beliefs (Beliefs about Medicine questionnaire, BMQ). Results were correlated to general and GH-specific adherence to medication.

Results

In the BMQ, 92.5% of the patients (n=99) reported a strong belief in the need for their medication, which correlated significantly with general adherence (rs = 0.325). Active coping was significantly related to general (rs = 0.307) and GH-specific adherence (rs = 0.226). Better mental QoL (rs = 0.210) but worse physical QoL (rs = -0.198; all p < 0.05) were related to higher GH-specific adherence. Older age was associated with a higher degree of active coping, a higher belief in the necessity of medication and worse physical QoL.

Conclusion

We provide preliminary data that most GHD patients on GHRx are strongly convinced of their need for medication and that adherence to GHRx is influenced by coping strategies and QoL. Patients with impaired psychological QoL are less able to translate their convictions into good adherence, a phenomenon to be addressed in future research.
Natural and Cultural Processes Influencing Gene Flow Among Wild (atoq papa), Weedy (araq papa and k’ipa papa), and Crop Potatoes in the Andean Region of Southern Peru
Authors: Parra-Rondinel Fabiola , Casas Alejandro , Begazo Domingo , Paco Amalia , Márquez Eusebia , Cruz Aldo , Segovia Jorge , Torres-García Ignacio , Zarazúa Mariana , Lizárraga Luis , Torres-Guevara Juan
Published: May 2021

The Andean region is one of the areas with the earliest signs of food production systems and highest agrobiodiversity of the world, which resulted from millennia of domestication in a context of high ecosystem heterogeneity and human cultures valuing diversity for risk management. FAO has reported nearly 4000 varieties of cultivated potatoes still grown in the Andes, 3000 of them currently occurring in Peru. Such diversity has enormous sources of variation in wild (atoq papa) and weedy (araq papaandk’ipa papa) potatoes that coexist with crops, but their variation, interactions and mechanisms influencing diversification processes still require studies. In order to have a panorama of the variation and mechanisms influencing it in a regional setting, we studied biocultural factors favoring potatoes diversity in communities of Cusco and Apurimac, Peru. Our study documented the regional variation of wild, weedy, and cultivated potatoes recognized by local Quechua people and conducted semi-structured interviews to document their use, cultural value, and strategies of gene flow management implemented. We also studied their phenology, floral biology, flower visitors, and conducted experimental crosses between the wildS. candolleanumand 30 varieties of cultivated potatoes. We identified the wild potatoesS. acaule,S. brevicauleandS. candolleanumand 53 varieties ofaraq papaused and managed by local people. The latter provide nearly one third of the annual consumption of tubers by people interviewed and are, therefore, highly valued, maintained and managed in crop fields (chacras). People recognized that crosses between wild, weedy, and cultivated potatoes occur, and identified flower visitors and frugivores consuming their berries. Overlap of blooming periods and flower visitors of wild, weedy, and cultivated potatoes was recorded. Almost all flower visitors are shared among the different potato species and varieties, the bumble bees being particularly relevant in pollination of all taxa studied. We recorded seed production in nearly 35% of the experimental crosses.K’ipa papasare sets of mixtures of plants resulting from remaining tubers of cultivated potatoes, but also those from seeds that may result from hybridization of wild, weedy, and cultivated potatoes. Since local people commonly usek’ipa papavarieties and some of them are kept for planting inchacras, sexual reproduction ink’ipa papasis possibly one main mechanism of variation and source of new varieties of crops. Maintaining wild and weedy potatoes, and the natural and cultural mechanisms of gene flow is crucial forin situconservation and generation of potato variation.
The Effects of Anthropogenic Sound and Artificial Light Exposure on Microbiomes: Ecological and Public Health Implications
Authors: Robinson Jake M. , Cameron Ross , Parker Brenda
Published: May 2021

Globally, anthropogenic sound and artificial light pollution have increased to alarming levels. Evidence suggests that these can disrupt critical processes that impact ecosystems and human health. However, limited focus has been given to the potential effects of sound and artificial light pollution on microbiomes. Microbial communities are the foundations of our ecosystems. They are essential for human health and provide myriad ecosystem services. Therefore, disruption to microbiomes by anthropogenic sound and artificial light could have important ecological and human health implications. In this mini-review, we provide a critical appraisal of available scientific literature on the effects of anthropogenic sound and light exposure on microorganisms and discuss the potential ecological and human health implications. Our mini-review shows that a limited number of studies have been carried out to investigate the effects of anthropogenic sound and light pollution on microbiomes. However, based on these studies, it is evident that anthropogenic sound and light pollution have the potential to significantly influence ecosystems and human health via microbial interactions. Many of the studies suffered from modest sample sizes, suboptimal experiments designs, and some of the bioinformatics approaches used are now outdated. These factors should be improved in future studies. This is an emerging and severely underexplored area of research that could have important implications for global ecosystems and public health. Finally, we also propose the photo-sonic restoration hypothesis: does restoring natural levels of light and sound help to restore microbiomes and ecosystem stability?
Discovery and Verification of an Immune-Related Gene Pairs Signature for Predicting Prognosis in Head and Neck Squamous Cell Carcinoma
Authors: He Jiqiang , Fang Xinqi , Han Mingming
Published: May 2021

The study of IRGPs to construct the prognostic signature in head and neck squamous cell carcinoma (HNSCC) has not yet elucidated. The objective of this study was to explore a novel model to predict the prognosis of HNSCC patients. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were set as training and validation cohorts, respectively. The least absolute shrinkage and selection operator (LASSO) and time-dependent ROC were employed to screen the highest frequency immune-related gene pairs (IRGPs) and their best cut-off value. Survival analysis, Cox regression analysis were applied to discover the effects of selected IRGPs signature on survival outcomes. The immune cell proportions were deconvoluted by the CIBERSORT method. After a couple of filtering, we obtained 22 highest frequency IRGPs. The overall survival time of HNSCC patients with a high score of IRGPs was shorter as compared to the ones with a low score in two independent datasets (P < 0.001). Six kinds of immune cells were found to be differentially distributed in the two different risk groups of HNSCC patients (P < 0.001). GO and GSEA analysis showed these differentially expressed genes enriched in multiple molecular functions. The new IRGPs signature probably confers a new insight into the prognosis prediction of HNSCC patients.
N6-Methyladenine in Eukaryotic DNA: Tissue Distribution, Early Embryo Development, and Neuronal Toxicity
Authors: Fernandes Sara B. , Grova Nathalie , Roth Sarah , Duca Radu Corneliu , Godderis Lode , Guebels Pauline , Mériaux Sophie B. , Lumley Andrew I. , Bouillaud-Kremarik Pascaline , Ernens Isabelle , Devaux Yvan , Schroeder Henri , Turner Jonathan D.
Published: May 2021

DNA methylation is one of the most important epigenetic modifications and is closely related with several biological processes such as regulation of gene transcription and the development of non-malignant diseases. The prevailing dogma states that DNA methylation in eukaryotes occurs essentially through 5-methylcytosine (5mC) but recently adenine methylation was also found to be present in eukaryotes. In mouse embryonic stem cells, 6-methyladenine (6mA) was associated with the repression and silencing of genes, particularly in the X-chromosome, known to play an important role in cell fate determination. Here, we have demonstrated that 6mA is a ubiquitous eukaryotic epigenetic modification that is put in place during epigenetically sensitive periods such as embryogenesis and fetal development. In somatic cells there are clear tissue specificity in 6mA levels, with the highest 6mA levels being observed in the brain. In zebrafish, during the first 120 h of embryo development, from a single pluripotent cell to an almost fully formed individual, 6mA levels steadily increase. An identical pattern was observed over embryonic days 7–21 in the mouse. Furthermore, exposure to a neurotoxic environmental pollutant during the same early life period may led to a decrease in the levels of this modification in female rats. The identification of the periods during which 6mA epigenetic marks are put in place increases our understanding of this mammalian epigenetic modification, and raises the possibility that it may be associated with developmental processes.
Multi-Omics Data Analyses Construct a Six Immune-Related Genes Prognostic Model for Cervical Cancer in Tumor Microenvironment
Authors: Xu Fangfang , Shen Jiacheng , Xu Shaohua
Published: May 2021

The cross-talk between tumor cells and the tumor microenvironment (TME) is an important factor in determining the tumorigenesis and progression of cervical cancer (CC). However, clarifying the potential mechanisms which trigger the above biological processes remains a challenge. The present study focused on immune-relevant differences at the transcriptome and somatic mutation levels through an integrative multi-omics analysis based on The Cancer Genome Atlas database. The objective of the study was to recognize the specific immune-related prognostic factors predicting the survival and response to immunotherapy of patients with CC. Firstly, eight hub immune-related prognostic genes were ultimately identified through construction of a protein–protein interaction network and Cox regression analysis. Secondly, 32 differentially mutated genes were simultaneously identified based on the different levels of immune infiltration. As a result, an immune gene-related prognostic model (IGRPM), including six factors (chemokine receptor 7 [CCR7], CD3d molecule [CD3D], CD3e molecule [CD3E], and integrin subunit beta 2 [ITGB2], family with sequence similarity 133 member A [FAM133A], and tumor protein p53 [TP53]), was finally constructed to forecast clinical outcomes of CC. Its predictive capability was further assessed and validated using the Gene Expression Omnibus validation set. In conclusion, IGRPM may be a promising prognostic signature to predict the prognoses and responses to immunotherapy of patients with CC. Moreover, the multi-omics study showed that IGRPM could be a novel therapeutic target for CC, which is a promising biomarker for indicating the immune-dominant status of the TME and revealing the potential mechanisms responsible for the tumorigenesis and progression of CC.
Functional Polymorphism in the NFE2L2 Gene Associated With Tuberculosis Susceptibility
Authors: Ji Guiyi , Zhang Miaomiao , Liu Qianqian , Wu Shouquan , Wang Yu , Chen Guo , Sandford Andrew J. , He Jian-Qing
Published: May 2021

Background

Nuclear transcription factor erythroid 2 p45-related factor 2 (Nrf2), encoded by NFE2L2, functions as a key transcription factor and regulates expression of antioxidant genes. Our study aimed to investigate the association of single nucleotide polymorphisms of NFE2L2 with tuberculosis (TB) and latent tuberculosis infection (LTBI) and the underlying causal mechanisms.

Methods

1950 unrelated Chinese Han participants were included in our two independent study groups. Five tag polymorphisms were selected and genotyped. The functional effects of the rs13005431 polymorphism were confirmed by dual-luciferase reporter assays and mRNA level comparisons.

Results

Rs13005431_C and rs2364723_G were associated with increased TB susceptibility (P = 0.010 and P = 0.041) after adjustment for confounding factors. rs6726395_A was associated with increased risk of active TB (P=0.035) in a comparison with the LTBI group. The frequency of haplotype rs1049751- rs13005431 AC was higher in the TB group (P =0.013), while frequency of haplotype AT was higher in the healthy control group (P =0.025). The luciferase activity of a plasmid with the rs13005431C-promoter was significantly lower than that of the rs13005431T-promoter. In addition, neutrophils with the CC/TC genotypes which were activated by GM-CSF showed a decreased level of NFE2L2 mRNA when compared with the rs13005431 TT genotype.

Conclusions

Our study suggests that allele C of rs13005431 might increase the susceptibility to TB by down-regulating the transcriptional activity of NFE2L2.
Transcriptional Changes in CD16+ Monocytes May Contribute to the Pathogenesis of COVID-19
Authors: Chilunda Vanessa , Martinez-Aguado Pablo , Xia Li C. , Cheney Laura , Murphy Aniella , Veksler Veronica , Ruiz Vanessa , Calderon Tina M. , Berman Joan W.
Published: May 2021

The COVID-19 pandemic has caused more than three million deaths globally. The severity of the disease is characterized, in part, by a dysregulated immune response. CD16+ monocytes are innate immune cells involved in inflammatory responses to viral infections, and tissue repair, among other functions. We characterized the transcriptional changes in CD16+ monocytes from PBMC of people with COVID-19, and from healthy individuals using publicly available single cell RNA sequencing data. CD16+ monocytes from people with COVID-19 compared to those from healthy individuals expressed transcriptional changes indicative of increased cell activation, and induction of a migratory phenotype. We also analyzed COVID-19 cases based on severity of the disease and found that mild cases were characterized by upregulation of interferon response and MHC class II related genes, whereas the severe cases had dysregulated expression of mitochondrial and antigen presentation genes, and upregulated inflammatory, cell movement, and apoptotic gene signatures. These results suggest that CD16+ monocytes in people with COVID-19 contribute to a dysregulated host response characterized by decreased antigen presentation, and an elevated inflammatory response with increased monocytic infiltration into tissues. Our results show that there are transcriptomic changes in CD16+ monocytes that may impact the functions of these cells, contributing to the pathogenesis and severity of COVID-19.
Oral Salmonella msbB Mutant as a Carrier for a Salmonella-Based Vaccine for Prevention and Reversal of Type 1 Diabetes
Authors: Cobb Jacob , Rawson Jeffrey , Gonzalez Nelson , Hensel Michael , Kandeel Fouad , Husseiny Mohamed I.
Published: May 2021

A therapy that includes an oral vaccine for type 1 diabetes (T1D) using live attenuated Salmonella MvP728 (ΔhtrA/ΔpurD), cytokines (IL10 and TGFβ) and preproinsulin (PPI) antigen in combination with a sub-therapeutic dose of anti-CD3 mAb was developed by our team. The vaccine combination therapy reduced insulitis and prevented and reversed diabetes in non-obese diabetic (NOD) mice. Here, we show the effectiveness of an alternative Salmonella mutant (ΔmsbB) as a carrier strain, which is anticipated to have lower risks of an inflammatory response and septicemia as a result of modification in the lipopolysaccharide (LPS) via detoxification of lipid A. This mutant strain proved to have highly reduced pathogenic side effects. Salmonella strain ΔmsbB expressed autoantigens and in combination with cytokines and anti-CD3 mAb, successfully prevented and reversed T1D to levels comparable to the previously used carrier strain ΔhtrA/ΔpurD. Additionally, the Salmonella msbB mutant resulted in higher rates of host cell infection. These results further demonstrate the potential of an oral Salmonella-based combined therapy in the treatment of early T1D.
Integration of Immunome With Disease-Gene Network Reveals Common Cellular Mechanisms Between IMIDs and Drug Repurposing Strategies
Authors: Devaprasad Abhinandan , Radstake Timothy R. D. J. , Pandit Aridaman
Published: May 2021

Objective

Development and progression of immune-mediated inflammatory diseases (IMIDs) involve intricate dysregulation of the disease-associated genes (DAGs) and their expressing immune cells. Identifying the crucial disease-associated cells (DACs) in IMIDs has been challenging due to the underlying complex molecular mechanism.

Methods

Using transcriptome profiles of 40 different immune cells, unsupervised machine learning, and disease-gene networks, we constructed the Disease-gene IMmune cell Expression (DIME) network and identified top DACs and DAGs of 12 phenotypically different IMIDs. We compared the DIME networks of IMIDs to identify common pathways between them. We used the common pathways and publicly available drug-gene network to identify promising drug repurposing targets.

Results

We found CD4+Treg, CD4+Th1, and NK cells as top DACs in inflammatory arthritis such as ankylosing spondylitis (AS), psoriatic arthritis, and rheumatoid arthritis (RA); neutrophils, granulocytes, and BDCA1+CD14+ cells in systemic lupus erythematosus and systemic scleroderma; ILC2, CD4+Th1, CD4+Treg, and NK cells in the inflammatory bowel diseases (IBDs). We identified lymphoid cells (CD4+Th1, CD4+Treg, and NK) and their associated pathways to be important in HLA-B27 type diseases (psoriasis, AS, and IBDs) and in primary-joint-inflammation-based inflammatory arthritis (AS and RA). Based on the common cellular mechanisms, we identified lifitegrast as a potential drug repurposing candidate for Crohn’s disease and other IMIDs.

Conclusions

Existing methods are inadequate in capturing the intricate involvement of the crucial genes and cell types essential to IMIDs. Our approach identified the key DACs, DAGs, common mechanisms between IMIDs, and proposed potential drug repurposing targets using the DIME network. To extend our method to other diseases, we built the DIME tool (https://bitbucket.org/systemsimmunology/dime/) to help scientists uncover the etiology of complex and rare diseases to further drug development by better-determining drug targets, thereby mitigating the risk of failure in late clinical development.
Autoantibody Discovery, Assay Development and Adoption: Death Valley, the Sea of Survival and Beyond
Authors: Fritzler Marvin J. , Choi May Y. , Satoh Minoru , Mahler Michael
Published: May 2021

Dating to the discovery of the Lupus Erythematosus (LE) cell in 1948, there has been a dramatic growth in the discovery of unique autoantibodies and their cognate targets, all of which has led to the availability and use of autoantibody testing for a broad spectrum of autoimmune diseases. Most studies of the sensitivity, specificity, commutability, and harmonization of autoantibody testing have focused on widely available, commercially developed and agency-certified autoantibody kits. However, this is only a small part of the spectrum of autoantibody tests that are provided through laboratories world-wide. This manuscript will review the wider spectrum of testing by exploring the innovation pathway that begins with autoantibody discovery followed by assessment of clinical relevance, accuracy, validation, and then consideration of regulatory requirements as an approved diagnostic test. Some tests are offered as “Research Use Only (RUO)”, some as “Laboratory Developed Tests (LDT)”, some enter Health Technology Assessment (HTA) pathways, while others are relegated to a “death valley” of autoantibody discovery and become “orphan” autoantibodies. Those that achieve regulatory approval are further threatened by the business world’s “Darwinian Sea of Survival”. As one example of the trappings of autoantibody progression or failure, it is reported that more than 200 different autoantibodies have been described in systemic lupus erythematosus (SLE), a small handful (~10%) of these have achieved regulatory approval and are widely available as commercial diagnostic kits, while a few others may be available as RUO or LDT assays. However, the vast majority (90%) are orphaned and languish in an autoantibody ‘death valley’. This review proposes that it is important to keep an inventory of these “orphan autoantibodies” in ‘death valley’ because, with the increasing availability of multi-analyte arrays and artificial intelligence (MAAI), some can be rescued to achieve a useful role in clinical diagnostic especially in light of patient stratification and precision medicine.
Knowledge From London and Berlin: Finding Threads to a Functional HIV Cure
Authors: Ding Jingyi , Liu Yanxi , Lai Yu
Published: May 2021

Despite the ability of combination antiretroviral therapy (cART) to increase the life expectancy of patients infected with human immunodeficiency virus (HIV), viral reservoirs persist during life-long treatment. Notably, two cases of functional cure for HIV have been reported and are known as the “Berlin Patient” and the “London Patient”. Both patients received allogeneic hematopoietic stem cell transplantation from donors with homozygous CCR5 delta32 mutation for an associated hematological malignancy. Therefore, there is growing interest in creating an HIV-resistant immune system through the use of gene-modified autologous hematopoietic stem cells with non-functional CCR5. Moreover, studies in CXCR4-targeted gene therapy for HIV have also shown great promise. Developing a cure for HIV infection remains a high priority. In this review, we discuss the increasing progress of coreceptor-based hematopoietic stem cell gene therapy, cART, milder conditioning regimens, and shock and kill strategies that have important implications for designing potential strategies aiming to achieve a functional cure for the majority of people with HIV.