bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatores ambientais e genéticos associados no desenvolvimento de Diabetes mellitus tipo 2: revisão sistemática
Authors: Mendonça Alexandre Menezes , Moura Joane Araújo , Araújo Paula Beatriz de Oliveira , Almeida Shirley Dantas
Published: December 2022

O Diabetes mellitus tipo 2 é a uma na qual a quantidade de insulina é incapaz de suprir a oferta de glicose, é uma das doenças que acomete pessoas no mundo. Os Fatores de desenvolvimentos das mesmas são fatores ambientais, e fatores genéticos, ambos podem ser retardados se as pessoas se submetam à um estilo de vida saudável. O objetivo principal do trabalho é buscar compreender e descrever os fatores ambientais e genéticos no DM2. Se trata de uma revisão sistemática de artigos publicados de 2012 à 2022 escritos em português, espanhol e inglês. Os critérios de exclusão foram: artigos publicados antes de 2015, que não sejam escritos em português, espanhol e inglês e que não tenham informações relativos ao DM2. Foram selecionados 19 artigos para este estudo, apenas 10 foram incluídos e 9 sustentaram os argumentos sugeridos pelos principais. Foram descritos como fatores ambientais: obesidade, hábitos alimentares ruins, sedentarismo, doenças cardiovasculares, tuberculose e hipertensão. Fatores genéticos: Polimorfismo dos genes XRCC3 T241M, XRCC1 399Gln e FTO rs3751812 e danos genéticos às células β-pancreáticas. Pode-se concluir que a base da patogênese do DMT2 são advindos de maus hábitos e sedentarismo e doenças de base, fatores que são facilmente prevenidos com mudanças na qualidade de vida, hábitos alimentares melhores e a prática de exercícios físicos. Já os demais fatores como os genéticos, a descoberta deles podem sugerir um estilo do qual venha retardar o acometimento do DMT2.
Fatores de risco associados ao infarto agudo do miocárdio: Revisão sistemática
Authors: Bussons Ana Julia Correa , Santo Janicleia Nascimento do Espírito , Gonçalves Paulo Victor Vieira
Published: December 2022

O infarto pode ocorrer em diversas partes do coração, depende de qual artéria foi obstruída. Em casos raros o infarto pode acontecer por contração da artéria, interrompendo o fluxo de sangue ou por desprendimento de um coágulo originado dentro do coração e que se aloja no interior dos vasos. O objetivo geral é analisar fatores de risco associados ao infarto agudo do miocárdio. Descrever a relação entre os diversos fatores de risco associados à ocorrência do infarto agudo do miocárdio e verificar as características das populações mais afetadas por condições predisponentes ao infarto e medidas de redução de risco. Se trata de um estudo de revisão sistêmica da literatura utilizando-se como bases de dados principais Scientific Electronic. Library Online (Scielo), A Biblioteca Virtual em Saúde do Ministério da Saúde (BVS), United States National Library of Medicine National Institutes of Health (PUBMED). O período analisado foi entre 2015 e 2022. Foram aplicados critérios do PRISMA. Com base nos 10 artigos analisados os fatores de risco que mais influenciam a ter infarto agudo do miocárdio são hipertensão arterial, diabetes mellitus, tabagismo, etilismo, sedentarismo, obesos e outros. De acordo com o tema abordado podemos ver que o infarto agudo do miocárdio pode acontecer tanto em jovens adultos como em idosos, a depender do hábito de vida que cada pessoa vive, é notório que as probabilidades de ocorrer IAM são maiores em pessoas que fumam, são sedentárias, possuem diabetes. mellitus, hipertensão arterial, dentre outros critérios.
Entraves da inclusão paterna no pré-natal
Authors: Dutra Brenda Sayd Silva , Correia Geovanna Santos , Torres Laura Oliveira , Nunes Júlia Sousa Santos
Published: December 2022

O envolvimento paterno no pré-natal é muito importante para as gestantes, o que torna necessário investigar os obstáculos causados pela ausência do parceiro nessa fase. O objetivo do estudo é analisar as dificuldades da inserção paterna no acompanhamento pré-natal, verificando o posicionamento da equipe de saúde, o que leva a essa omissão por parte dos parceiros e a percepção da gestante quanto a essa ausência. Trata-se de uma pesquisa exploratória de finalidade básica, com abordagem qualitativa e quantitativa realizada em 06 unidades de saúde de Vitória da Conquista-Bahia, com duração de 06 meses, no período de agosto a setembro. Os dados qualitativos coletados foram dispostos conforme a análise de dados de Bardin 2016, já os quantitativos, por meio de tabelas realizadas no Excel divididas em dados obtidos. Os resultados do presente estudo relatam a falta de interesse dos pais em comparecer ao pré-natal e como as gestantes estão conformadas com a situação mesmo se sentindo inseguras nesse momento, bem como a falta de incentivo por parte dos profissionais. O presente estudo demonstrou a total falta de interesse tanto dos pais em participar do pré-natal bem como dos profissionais de saúde em incentivá-los nesse momento visto que não possuem preparo e conhecimento suficiente. Apontando a necessidade de novos programas educativos que possam contribuir com a inserção dos pais, promovendo conhecimento e interesse dos mesmos, bem como, proporcionar a qualificação dos profissionais de enfermagem com investimentos na saúde e no conhecimento, ampliando o acesso aos cuidados com a educação permanente e continuada.
Environmental Hazards of Heavy Metal Pollution and Toxicity: A Review
Authors: Kaushik Pallavi , Khandelwal Renu , Rawat Neha , Sharma Mukesh Kumar
Published: December 2022

Metals and especially heavy metals are one of the major constituents of environmental pollution. The sources of heavy metal pollution can be geogenic or anthropogenic. The man-made sources include fumes, metal laden dust or food components. Although, many metals are essential for animal metabolism but a dose exceeding the required concentration is often deleterious. The hazardous nature of these heavy metals has been extensively studied in human, animal and plants showing various toxicological impacts of toxic metals. The acute or chronic exposure of heavy metals to animals and human can result in severe injury to the structure and function of vital organs as liver, kidney, brain along with systemic disease conditions. The growth of plants is also severely affected by the intake of metallic compounds through the mineral and water absorption route. The deleterious effects on plants range from symptoms of injury to metabolic, enzymatic, and growth inhibition. The study of heavy metal pollution and the subsequent impact to flora and fauna can contribute in spreading public awareness and sensitizing policy makers to develop strategic planning in order to reduce the pollution and implement biological protection strategies.
A Critical Analysis of Drugs Used in Anticancer Therapy Isolated from the Catharanthus
roseus : A Review
Authors: Kumar Anil , Patra Kamal Kant , Keshamma E. , Nirmalkar Shyamlal , Sinha Pragyan Paramita , Lokare Priya
Published: December 2022

Cancer is an abnormal pattern of growth which has ability to spread to the other parts of the body. Many treatment options are available currently such as chemotherapy, radiotherapy and surgery. Presently increasing number of cancer cases globally has made responsible community and researchers to pay attention to establish a sustainable therapy option which is effective both in terms of cost and treatment. Medicinal plants could be the best option for extracting anticancer drugs. Majority of the anticancer drugs currently being used are extracted from natural sources. Catharanthus roseus also known as “Madagascar periwinkle”, belongs to the family Apocynaceae. This splendid and marvelous shrub is a good source of indole monoterpenes and alkaloids which are used as anticancer, antiproliferative and antimitotic drugs. Anticancer drugs extracted from C. roseus, their mechanisms of action, their potential and complications associated with them are discussed.
PERILAKU NON PLAYER CHARACTER (NPC) PADA GAME FPS “ZOMBIE COLONIAL WARS” MENGGUNAKAN FINITE STATE MACHINE (FSM)
Authors: Astuti Yulia Windi , Yunus Amak , Ahsan Moh.
Published: December 2022

Penerapan kecerdasan buatan (AI) dalam sebuah game merupakan salah satu inovasi teknologi. Variasi game salah satunya adalah First Person Shooter (FPS). Kecerdasan buatan yang dikembangkan untuk merancang perilaku Non Player Character (NPC) dimana NPC dapat berperilaku secara bertahap dan berurutan sesuai state. Oleh sebab itu dikembangkan dengan menerapkan metode Finite State Machine (FSM) pada game “Zombie Colonial Wars”. Penerapan metode Finite State Machine (FSM) dalam game Zombie Colonial Wars berfungsi untuk melihat variasi respon perilaku pada NPC sesuai interaksi yang dilakukan oleh player. Hasil dari penelitian ini adalah game zombie colonial wars menghasilkan sebuah kecerdasan buatan pada perilaku NPC dengan mengimplementasikan metode finite state machine sehingga musuh dapat berperilaku berdasarkan interaksi yang telah dilakukan oleh player.
IMPLEMENTASI TEXT MINING DALAM PENGELOMPOKAN DATA TWEET PERTANIAN INDONESIA DENGAN K-MEANS
Authors: Irsyad Hafiz , Pribadi M Rizky
Published: December 2022

Pertanian 4.0 merupakan suatu gebrakan dimana konsumen lebih dekat pada petani atau para perusahaan pertanian. Salah satu bentuk pertanian 4.0 ini adalah pertanian digital agar setiap kegiatan pertanian dapat terekam, menghasilkan data dan informasi terhadap bentuk dukungan untuk aktivitas pertanian di Indonesia. Pada penelitian ini menerapkan text mining pada data tweet agar dapat mengelompokkan data tersebut dengan menggunakan Algoritma K-Means. Dalam implementasi peneletian ini dibantu dengan menggunakan 2 tools, yakni orange tools untuk melakukan text processing dan Rapidminer untuk melakukan pengolahan algoritma KMeans. Hasil dari penerapan algortima K-Means terdapat 5 klaster, yaitu Pangan, Produksi, Lahan, Ekspor dan Teknologi. Dari 5 (lima) klaster tersebut kemudian menggunakan operator % performance pada rapidminer untuk mendapatkan rata-rata akurasi terhadap klaster tersebut adalah 0.344%. maka hasil dari penelitian ini terdapat 2 klaster yang nilainya tinggi yaitu kluster 0 Pangan dengan nilai 0.528% dan kluster 2 Produksi dengan nilai 0.523% dan untuk kluster yang nilai paling rendah adalah klaster 3 tentang ekspor dengan nilai 0.123% dengan hasil tersbut artinya implementasi text mining dapat dilakukan pada tools rapidminer.
IMPLEMENTASI METODE IMPORTANCE PERFORMANCE ANALYSIS UNTUK PENGUKURAN KUALITAS SISTEM INFORMASI AKADEMIK
Authors: Immanuel Gracecilla Aprillia , Setiawan Rudy
Published: December 2022

Universitas Ma Chung dalam membantu kegiatan akademik mahasiswa, menggunakan sistem informasi akademik (SIAKAD) yaitu Ma Chung Integrated System (MAC IS). Banyak fitur MAC IS ini dapat mendukung kebutuhan informasi akademik mahasiswa. Saat ini sistem akademik Universitas Ma Chung yaitu MAC IS masih sedang dalam proses pengembangan dan perbaikan agar dapat memenuhi kebutuhan pengguna yaitu mahasiswa dalam memperoleh informasi akademiknya. Selain itu juga perlu dilakukan pengukuran sejauh mana kepuasan pengguna dalam menggunakan sistem informasi akademik ini. Metode yang digunakan dalam melakukan perhitungan menggunakan metode Importance Performance Analysis (IPA). Dari hasil perhitungan IPA akan dipetakan ke dalam diagram kartesius yang dapat menunjukkan indikator yang perlu dikembangkan lagi atau yang perlu dipertahankan. Hasil penelitian ini menunjukkan penilaian kinerja MAC IS sebesar 77% dan termasuk dalam kategori baik. Untuk indikator yang masuk dalam kuadran 1 adalah dari variabel usability pada pernyataan nomor 1 yaitu pengguna mudah mempelajari situs.
ANALISIS DATA SCIENCE PADA STRUKTUR DATA KEPADATAN PENDUDUK KOTA MALANG
Authors: Witak Damianus Daton , Wiguna Anggri Sartika , Nugraha Danang Aditya
Published: December 2022

Kepadatan penduduk indonesia meningkat cukup melesat dari tahun ketahun, bersumber dari sensus pada tahun 2019 kepadatan penduduk indonesia sebesar 267 juta jiwa (BPS, 2019). Kepadatan penduduk mengakibatkan dampak/efek meningkatnya pemukiman semakin padat, persaingan perusahaan yang tidak sehat, kerawanan sosial, penyediaan air bersih semakin berkurang, kemacetan semakin meningkat. Oleh karena itu Data Science sendiri mengacu pada metode forecsting yang digunakan untuk peramalan jangka panjang, jangka menengah,maupun pendek, dalam suatu perusahaan yang diharapkan dapat membantu memecahkan masalah dalam mengestimasi laju kepadatan penduduk. Untuk mengetahui jumlah kepadatan penduduk kota malang di tahun yang akan datang maka perlu dilakukan sistem untuk memprediksi kepadatan penduduk 10 tahun sebelumnya sehingga hasil dari peramalam ditahun sebelumnya akan menjadi penentu peramalan data kepadatan penduduk ditahun yang akan datang. Teknik penelitian yang digunakan terdiri dari teknik pengumpulan data, teknik peramalan data, teknik analisa hasil dan kesimpulan. Hasil dari peramalan tersebut di ambil dari nilai error MAD, MSE dan MAPE yang terkecil dari hasil peramalan Kepadatan Penduduk Kota Malang.
IMPLEMENTASI ALGORITMA RIVEST CODE 4 (RC4) UNTUK PENYANDIAN SMS PADA TELEPON SELULAR
Authors: Irsyad Hafiz , Taqwiym Akhsani , Wijaya Novan
Published: December 2022

Komunikasi SMS merupakan fitur dari telepon selular yang user friendly, useful, sangat standar dan sangat mudah digunakan dan banyak orang yang menggunakan media tersebut sebagai mengirimkan informasi baik secara rahasia atau terbuka untuk umum. Kondisi seperti inilah yang dimanfaatkan oleh intruder untuk mengambil informasi secara illegal dengan menggunakan informasi tersebut. Ada banyak cara untuk melakukan proses pengamanan informasi yang kita kirimkan tersebut, diantaranya menggunakan teknik kriptografi. Algoritma RC4 merupakan algoritma kriptografi yang cukup sederhana dan tidak telalu rumit. Teknik kriptografi yang cocok diimplementasikan pada telepon selular adalah teknik kriptografi dengan algoritma kriptografi yang sederhana dan tidak terlalu rumit. Telepon selular pada umumnya tidak memiliki processor yang cepat layaknya komputer, sehingga untuk menerapkan teknik kriptografi diperlukan pemilihan yang tepat. SMS adalah suatu layanan yang memungkinkan pengguna telepon selular mengirim atau menerima pesan-pesan singkat dengan cepat dan dengan biaya yang relatif murah. Penelitian yang diharapkan mampu melakukan proses enkripsi dari inforamsi sehingga tidak bisa diakses secara illegal.
Everyday Racial Trauma and Psychosis: Diagnosis and Presentation
Authors: Pennycooke Earl
Published: December 2022

In this article the author reflects on racism from a personal and socio-political angle. He describes how the continuous repetition of racist trauma in personal and societal life not only damages the psyche of individuals but also has a detrimental effect on interpersonal and intergenerational relations. He further describes the work of USEMI, a project which offers psychoanalytic psychotherapy to Black men, and by doing so presents the possibilities and limitations of psychoanalysis to help those suffering under the psychological effects of racism.
A novel approach for tetrahedral-element-based finite element simulations of anisotropic hyperelastic intervertebral disc behavior
Authors: Fasser Marie-Rosa , Kuravi Ramachandra , Bulla Marian , Snedeker Jess G. , Farshad Mazda , Widmer Jonas
Published: December 2022

Intervertebral discs are microstructurally complex spinal tissues that add greatly to the flexibility and mechanical strength of the human spine. Attempting to provide an adjustable basis for capturing a wide range of mechanical characteristics and to better address known challenges of numerical modeling of the disc, we present a robust finite-element-based model formulation for spinal segments in a hyperelastic framework using tetrahedral elements. We evaluate the model stability and accuracy using numerical simulations, with particular attention to the degenerated intervertebral discs and their likely skewed and narrowed geometry. To this end, 1) annulus fibrosus is modeled as a fiber-reinforced Mooney-Rivlin type solid for numerical analysis. 2) An adaptive state-variable dependent explicit time step is proposed and utilized here as a computationally efficient alternative to theoretical estimates. 3) Tetrahedral-element-based FE models for spinal segments under various loading conditions are evaluated for their use in robust numerical simulations. For flexion, extension, lateral bending, and axial rotation load cases, numerical simulations reveal that a suitable framework based on tetrahedral elements can provide greater stability and flexibility concerning geometrical meshing over commonly employed hexahedral-element-based ones for representation and study of spinal segments in various stages of degeneration.
A computational method for estimating trunk muscle activations during gait using lower extremity muscle synergies
Authors: Li Geng , Ao Di , Vega Marleny M. , Shourijeh Mohammad S. , Zandiyeh Payam , Chang Shuo-Hsiu , Lewis Valerae O. , Dunbar Nicholas J. , Babazadeh-Naseri Ata , Baines Andrew J. , Fregly Benjamin J.
Published: December 2022

One of the surgical treatments for pelvic sarcoma is the restoration of hip function with a custom pelvic prosthesis after cancerous tumor removal. The orthopedic oncologist and orthopedic implant company must make numerous often subjective decisions regarding the design of the pelvic surgery and custom pelvic prosthesis. Using personalized musculoskeletal computer models to predict post-surgery walking function and custom pelvic prosthesis loading is an emerging method for making surgical and custom prosthesis design decisions in a more objective manner. Such predictions would necessitate the estimation of forces generated by muscles spanning the lower trunk and all joints of the lower extremities. However, estimating trunk and leg muscle forces simultaneously during walking based on electromyography (EMG) data remains challenging due to the limited number of EMG channels typically used for measurement of leg muscle activity. This study developed a computational method for estimating unmeasured trunk muscle activations during walking using lower extremity muscle synergies. To facilitate the calibration of an EMG-driven model and the estimation of leg muscle activations, EMG data were collected from each leg. Using non-negative matrix factorization, muscle synergies were extracted from activations of leg muscles. On the basis of previous studies, it was hypothesized that the time-varying synergy activations were shared between the trunk and leg muscles. The synergy weights required to reconstruct the trunk muscle activations were determined through optimization. The accuracy of the synergy-based method was dependent on the number of synergies and optimization formulation. With seven synergies and an increased level of activation minimization, the estimated activations of the erector spinae were strongly correlated with their measured activity. This study created a custom full-body model by combining two existing musculoskeletal models. The model was further modified and heavily personalized to represent various aspects of the pelvic sarcoma patient, all of which contributed to the estimation of trunk muscle activations. This proposed method can facilitate the prediction of post-surgery walking function and pelvic prosthesis loading, as well as provide objective evaluations for surgical and prosthesis design decisions.
Conformational switch and multiple supramolecular structures of a newly identified self-assembling protein-mimetic peptide from Pseudomonas aeruginosa YeaZ protein
Authors: Fasola Elettra , Alboreggia Giulia , Pieraccini Stefano , Oliva Francesco , Agharbaoui Fatima Ezzahra , Bollati Michela , Bertoni Giovanni , Recchia Sandro , Marelli Marcello , Piarulli Umberto , Pellegrino Sara , Gazzola Silvia
Published: December 2022

Protein-mimetic peptides (PMPs) are shorter sequences of self-assembling proteins, that represent remarkable building blocks for the generation of bioinspired functional supramolecular structures with multiple applications. The identification of novel aminoacidic sequences that permit the access to valuable biocompatible materials is an attractive area of research. In this work, in silico analysis of the Pseudomonas aeruginosa YeaZ protein (PaYeaZ) led to the identification of a tetradecapeptide that represents the shortest sequence responsible for the YeaZ-YeaZ dimer formation. Based on its sequence, an innovative 20-meric peptide, called PMP-2, was designed, synthesized, and characterized in terms of secondary structure and self-assembly properties. PMP-2 conserves a helical character and self-assembles into helical nanofibers in non-polar solvents (DMSO and trifluoroethanol), as well as in dilute (0.5 mM) aqueous solutions. In contrast, at higher concentrations (>2 mM) in water, a conformational transition from α-helix to β-sheet occurs, which is accompanied by the Protein-mimetic peptide aggregation into 2D-sheets and formation supramolecular gel in aqueous environment. Our findings reveal a newly identified Protein-mimetic peptide that could turn as a promising candidate for future material applications.
Ligand-assisted structure tailoring of highly luminescent Cu-In-Zn-S/ZnS//ZnS quantum dots for bright and stable light-emitting diodes
Authors: Zang Shuaipu , Zhang Xuhui , Sun Yingying , Li Ning , Wang Lei , Li Lin Song
Published: December 2022

Harnessing environment-friendly and low-cost multinary Cu-In-Zn-S quantum dots (QDs) as emitters for light-emitting diodes (LEDs) has attracted great attention for display and lighting application. However, suboptimal QD structure is a huge obstacle, which results in serious non-radiative recombination and efficiency roll-off. Herein, we synthesized structure-tailored Cu-In-Zn-S/ZnS//ZnS QDs by improving the reactivity of shell growth by 2-ethylhexanoic acid (EHA) ligands. The EHA-assisted shell growth can boost an extended alloyed layer at the core-shell interface and a smoothed confinement barrier, which effectively passivate the interface defects and suppress Förster resonance energy transfer (FRET) process. These synthesized QDs display a bright photoluminescence emission (quantum yield of 83%) and a larger size of 8.4 nm. Moreover, the resulting LEDs based on the EHA-assisted QDs exhibit a maximum luminance of 8074 cd/m2, and a current efficiency of 7.3 cd/A with a low efficiency roll-off. Our results highlight a remarkable ligand strategy to tailor the QD structure for high performance QD-based LEDs.
Identifying distinctive tissue and fecal microbial signatures and the tumor-promoting effects of deoxycholic acid on breast cancer
Authors: Wang Na , Yang Jun , Han Wenjie , Han Mengzhen , Liu Xiaolin , Jiang Lei , Cao Hui , Jing Mingxi , Sun Tao , Xu Junnan
Published: December 2022

Introduction

A growing body of evidence indicates that the dysbiosis of both mammary and intestinal microbiota is associated with the initiation and progression of breast tumors. However, the microbial characteristics of patients with breast tumors vary widely across studies, and replicable biomarkers for early-stage breast tumor diagnosis remain elusive.

Methods

We demonstrate a machine learning-based method for the analysis of breast tissue and gut microbial differences among patients with benign breast disease, patients with breast cancer (BC), and healthy individuals using 16S rRNA sequence data retrieved from eight studies. QIIME 2.0 and R software (version 3.6.1) were used for consistent processing. A naive Bayes classifier was trained on the RDP v16 reference database to assign taxonomy using the Vsearch software.

Results

After re-analyzing with a total of 768 breast tissue samples and 1,311 fecal samples, we confirmed that Halomonas and Shewanella were the most representative genera of BC tissue. Bacteroides are frequently and significantly enriched in the intestines of patients with breast tumor. The areas under the curve (AUCs) of random forest models were 74.27% and 68.08% for breast carcinoma tissues and stool samples, respectively. The model was validated for effectiveness via cohort-to-cohort transfer (average AUC =0.65) and leave-one-cohort-out (average AUC = 0.66). The same BC-associated biomarker Clostridium_XlVa exists in the tissues and the gut. The results of the in-vitro experiments showed that the Clostridium-specific-related metabolite deoxycholic acid (DCA) promotes the proliferation of HER2-positive BC cells and stimulates G0/G1 phase cells to enter the S phase, which may be related to the activation of peptide-O-fucosyltransferase activity functions and the neuroactive ligand–receptor interaction pathway.

Discussion

The results of this study will improve our understanding of the microbial profile of breast tumors. Changes in the microbial population may be present in both the tissues and the gut of patients with BC, and specific markers could aid in the early diagnosis of BC. The findings from in-vitro experiments confirmed that Clostridium-specific metabolite DCA promotes the proliferation of BC cells. We propose the use of stool-based biomarkers in clinical application as a non-invasive and convenient diagnostic method.
Composition and changes of blood microbiota in adult patients with community-acquired sepsis: A pilot study from bench to bedside
Authors: Szabó Bálint Gergely , Kiss Rebeka , Makra Nóra , Pénzes Kinga , Vad Eszter , Kamotsay Katalin , Szabó Dóra , Ostorházi Eszter
Published: December 2022

Background

Characteristics of the blood microbiota among adult patients with community-acquired sepsis are poorly understood. Our aim was to analyze the composition of blood microbiota in adult patients with community-acquired sepsis, and correlate changes with non-septic control patients.

Methods

A prospective observational study was carried out by including adult patients hospitalized for community-acquired sepsis at our center between January and November 2019, by random selection from a pool of eligible patients. Study inclusion was done on the day of sepsis diagnosis. Community acquisition was ascertained by a priori exclusion criteria; sepsis was defined according to the SEPSIS-3 definitions. Each included patient was matched with non-septic control patients by age and gender in a 1:1 fashion enrolled from the general population. Conventional culturing with BacT/ALERT system and 16S rRNA microbiota analysis were performed from blood samples taken in a same time from a patient. Abundance data was analyzed by the CosmosID HUB Microbiome software.

Results

Altogether, 13 hospitalized patients were included, 6/13 (46.2%) with sepsis and 7/13 (53.8%) with septic shock at diagnosis. The most prevalent etiopathogen isolated from blood cultures was Escherichia coli, patients mostly had intraabdominal septic source. At day 28, all-cause mortality was 15.4% (2/13). Compared to non-septic control patients, a relative scarcity of Faecalibacterium, Blautia, Coprococcus and Roseburia genera, with an abundance of Enhydrobacter, Pseudomonas and Micrococcus genera was observed among septic patients. Relative differences between septic vs. non-septic patients were more obvious at the phylum level, mainly driven by Firmicutes (25.7% vs. 63.1%; p<0.01) and Proteobacteria (36.9% vs. 16.6%; p<0.01). The alpha diversity, quantified by the Chao1 index showed statistically significant difference between septic vs. non-septic patients (126 ± 51 vs. 66 ± 26; p<0.01). The Bray-Curtis beta diversity, reported by principal coordinate analysis of total hit frequencies, revealed 2 potentially separate clusters among septic vs. non-septic patients.

Conclusion

In adult patients with community-acquired sepsis, specific changes in the composition and abundance of blood microbiota could be detected by 16S rRNA metagenome sequencing, compared to non-septic control patients. Traditional blood culture results only partially correlate with microbiota test results.
Genomic characterization of Plasmodium falciparum genes associated with anti-folate drug resistance and treatment outcomes in eastern India: A molecular surveillance study from 2008 to 2017
Authors: Das Sabyasachi , Tripathy Satyajit , Das Ankita , Sharma Meenakshi Kumari , Nag Ayan , Hati Amiya Kumar , Roy Somenath
Published: December 2022

Introduction

After being used vigorously for the previous two decades to treat P. falciparum, chloroquine and sulfadoxine-pyrimethamine were replaced in 2009 with an artemisinin-based combination therapy (artesunate-sulfadoxine-pyrimethamine) in an effort to combat multidrug-resistant parasites.

Methods

We set out to assess the genetic variants of sulfadoxine-pyrimethamine resistance and the effectiveness of its treatment in eastern India prior to, during, and 6 to 8 years following the introduction of the new pharmacological regime. In 2008-2009, 318 P. falciparum–positive patients got the recommended doses of sulfadoxine-pyrimethamine. We used 379 additional isolates from 2015 to 2017 in addition to the 106 isolates from 2010. All 803 isolates from two study sites underwent in vitro sulfadoxine-pyrimethamine sensitivity testing and genomic characterisation of sulfadoxine-pyrimethamine resistance (pfdhfr and pfdhps).

Results

In Kolkata and Purulia, we observed early treatment failure in 30.7 and 14.4% of patients, respectively, whereas recrudescence was found in 8.1 and 13.4% of patients, respectively, in 2008–2009. In 2017, the proportion of in vitro pyrimethamine and sulfadoxine resistance steadily grew in Kolkata and Purulia despite a single use of sulfadoxine-pyrimethamine. Treatment failures with sulfadoxine-pyrimethamine were linked to quintuple or quadruple pfdhfr- pfdhps mutations (AICII-AGKAT, AICII-AGKAA, AICII-SGKGT, AICII-AGKAA, AICNI-AGKAA) in 2008–2009 (p < 0.001). The subsequent spread of mutant-haplotypes with higher in vitro sulfadoxine-pyrimethamine resistance (p < 0.001), such as the sextuple (dhfr-AIRNI+dhps-AGEAA, dhfr-ANRNL+dhps-AGEAA) and septuple (dhfr-AIRNI+dhps-AGEAT), mutations were observed in 2015-2017.

Discussion

This successive spread of mutations with high in vitro sulfadoxine-pyrimethamine resistance confirmed the progressive increase in antifolate resistance even after an 8-year withdrawal of sulfadoxine-pyrimethamine.
Liberatory school counseling practices to promote freedom dreaming for Black youth
Authors: Mayes Renae D. , Edirmanasinghe Natalie , Ieva Kara , Washington Ahmad R.
Published: December 2022

The American School Counseling Association calls for professional school counselors to support the holistic development and success of all students. However, the field of school counseling is riddled with practices that have harmed and dehumanized Black students. For example, school counselors engage in practices (e.g., social–emotional learning and vocational guidance), which work to reinforce white supremacy and dehumanize Black students. Further, school counselors may also contribute to the ways that the basic and unique needs of Black students are overlooked, leading to the continued systemic adultification of Black students. What is needed is a radical imagination of school counseling, which centers on homeplace as the foundation in order to engage in freedom dreaming. In this article, the authors engage this radical imagination to detail an antiracist view of school counseling practice that embraces freedom dreaming and homeplace through healing and Indigenous educational practices, youth-led school counseling, and critical hip-hop practices to promote joy, creativity, power, love, resistance, and liberation.
Case report: TP53 and RB1 loss may facilitate the transformation from lung adenocarcinoma to small cell lung cancer by expressing neuroendocrine markers
Authors: Li Jun , Wei Bing , Feng Junnan , Wu Xinxin , Chang Yuxi , Wang Yi , Yang Xiuli , Zhang Haiyan , Han Sile , Zhang Cuiyun , Zheng Jiawen , Groen Harry J. M. , van den Berg Anke , Ma Jie , Li Hongle , Guo Yongjun
Published: December 2022

Introduction

Transformation from lung adenocarcinoma (LUAD) to small cell lung cancer (SCLC) is one of the mechanisms responsible for acquired EGFR-TKIs resistance. Although it rarely happens this event determines a rapid disease deterioration and needs specific treatment.

Patient and method

We report a case of 75-year-old LUAD female with a p.L858R mutation in Epidermal Growth Factor Receptor (EGFR) who presented with SCLC transformation after responding to first line osimertinib treatment for only 6 months. To understand the underlying molecular mechanism, we retrospectively sequenced the first (LUAD) and the second (SCLC) biopsy using a 56 multi-gene panel. Immunohistochemistry (IHC) staining and Fluorescence In Situ Hybridization (FISH) was applied to confirm the genetic aberrations identified.

Results

EGFR p.E709A and p.L858R, Tumor Protein p53 (TP53) p.A159D and Retinoblastoma 1 (RB1) c.365-1G>A were detected in both the diagnostic LUAD and transformed SCLC samples. A high copy number gain for Proto-Oncogene C-Myc (MYC) and a Phosphoinositide 3-Kinase Alpha (PIK3CA) p.E545K mutation were found in the transformed sample specifically. Strong TP53 staining and negative RB1 staining were observed in both LUAD and SCLC samples, but FISH only identified MYC amplification in SCLC tissue.

Conclusion

We consider the combined presence of MYC amplification with mutations in TP53 and RB1 as drivers of SCLC transformation. Our results highlight the need to systematically evaluate TP53 and RB1 status in LUAD patients to offer a different therapeutic strategy.
A suitable method for alpine wetland delineation: An example for the headwater area of the yellow river, Tibetan Plateau
Authors: Yin Tao , Feng Yuqing , Liang Sihai , Wang Guangjun , Yuan Ning , Yan Dezhao , Wu Pan , Kuang Xingxing , Wan Li
Published: December 2022

Alpine wetlands are one of the most important ecosystems in the Three Rivers Source Area, China, which plays an important role in regulating the regional hydrological cycle and carbon cycle. Accordingly, Wetland area and its distribution are of great significance for wetland management and scientific research. In our study, a new wetland classification model which based on geomorphological types and combine object-oriented and decision tree classification model (ODTC), and used a new wetland classification system to accurately extract the wetland distributed in the Headwater Area of the Yellow River (HAYR) of the Qinghai-Tibet Plateau (QTP), China. The object-oriented method was first used to segment the image into several areas according to similarity in Pixels and Textures, and then the wetland was extracted through a decision tree constructed based on geomorphological types. The wetland extracted by the model was compared with that by other seven commonly methods, such as support vector machine (SVM) and random forest (RF), and it proved the accuracy was improved by 10%–20%. The overall classification accuracy rate was 98.9%. According to our results, the HAYR’s wetland area is 3142.3 km2, accounting for 16.1% of the study area. Marsh wetlands and flood wetlands accounted for 37.7% and 16.7% respectively. A three-dimensional map of the area showed that alpine wetlands in the research region are distributed around lakes, piedmont groundwater overflow belts, and inter-mountain catchment basin. This phenomenon demonstrates that hydrogeological circumstances influence alpine wetlands’ genesis and evolution. This work provides a new approach to investigating alpine wetlands.
Governance strategies for end-of-life electric vehicle battery recycling in China: A tripartite evolutionary game analysis
Authors: Wei Lang , Wang Cuixia , Li Yaqin
Published: December 2022

End-of-life (EOL) electric vehicle (EV) batteries have both economic and environmental benefits if recycled in an environmentally friendly manner while they may cause environmental pollution if treated improperly. China is currently working hard to promote the development of a circular economy by EOL EV battery recycling. However, conflicts of interest among electric vehicle manufacturers (EVMs), consumers, and the government often hinder efficient recycling. This study constructs a tripartite evolutionary game model under the condition of bounded rationality, analyzes the evolutionary stability strategy of three participants, and combines with numerical simulation to explore the feasible governance strategies of EOL EV battery recycling. The results show that four evolutionary stable strategies (ESSs) correspond to the three stages of the EOL EV battery recycling industry: early stage, development stage, and maturity stage. In the early stage, the punishment strategy is more critical to motivate EVMs and consumers to actively participate in battery recycling. The subsidy mechanisms can influence the strategic choices of the three participants, but the excessive subsidy is not conducive to the sustainable development of the EOL EV battery industry. In addition, when the industry matures, the government will gradually decrease intervention, thereby realizing the development path of EOL EV battery recycling from exogenous government supervision to endogenous profit drive.
Benchmarking automated cell type annotation tools for single-cell ATAC-seq data
Authors: Wang Yuge , Sun Xingzhi , Zhao Hongyu
Published: December 2022

As single-cell chromatin accessibility profiling methods advance, scATAC-seq has become ever more important in the study of candidate regulatory genomic regions and their roles underlying developmental, evolutionary, and disease processes. At the same time, cell type annotation is critical in understanding the cellular composition of complex tissues and identifying potential novel cell types. However, most existing methods that can perform automated cell type annotation are designed to transfer labels from an annotated scRNA-seq data set to another scRNA-seq data set, and it is not clear whether these methods are adaptable to annotate scATAC-seq data. Several methods have been recently proposed for label transfer from scRNA-seq data to scATAC-seq data, but there is a lack of benchmarking study on the performance of these methods. Here, we evaluated the performance of five scATAC-seq annotation methods on both their classification accuracy and scalability using publicly available single-cell datasets from mouse and human tissues including brain, lung, kidney, PBMC, and BMMC. Using the BMMC data as basis, we further investigated the performance of these methods across different data sizes, mislabeling rates, sequencing depths and the number of cell types unique to scATAC-seq. Bridge integration, which is the only method that requires additional multimodal data and does not need gene activity calculation, was overall the best method and robust to changes in data size, mislabeling rate and sequencing depth. Conos was the most time and memory efficient method but performed the worst in terms of prediction accuracy. scJoint tended to assign cells to similar cell types and performed relatively poorly for complex datasets with deep annotations but performed better for datasets only with major label annotations. The performance of scGCN and Seurat v3 was moderate, but scGCN was the most time-consuming method and had the most similar performance to random classifiers for cell types unique to scATAC-seq.
PSME2 identifies immune-hot tumors in breast cancer and associates with well therapeutic response to immunotherapy
Authors: Wu Cen , Zhong Ren , Sun Xiaofei , Shi Jiajie
Published: December 2022

Breast cancer (BrCa) is a heterogeneous disease, which leads to unsatisfactory prognosis in females worldwide. Previous studies have proved that tumor immune microenvironment (TIME) plays crucial roles in oncogenesis, progression, and therapeutic resistance in Breast cancer. However, biomarkers related to TIME features have not been fully discovered. Proteasome activator complex subunit 2 (PSME2) is a member of proteasome activator subunit gene family, which is critical to protein degradation mediated by the proteasome. In the current research, we comprehensively analyzed the expression and immuno-correlations of Proteasome activator complex subunit 2 in Breast cancer. Proteasome activator complex subunit 2 was significantly upregulated in tumor tissues but associated with well prognosis. In addition, Proteasome activator complex subunit 2 was overexpressed in HER2-positive Breast cancer but not related to other clinicopathological features. Interestingly, Proteasome activator complex subunit 2 was positively related to immune-related processes and identified immuno-hot TIME in Breast cancer. Specifically, Proteasome activator complex subunit 2 was positively correlated with immunomodulators, tumor-infiltrating immune cells (TIICs), immune checkpoints, and tumor mutation burden (TMB) levels. Moreover, the positive correlation between Proteasome activator complex subunit 2 and PD-L1 expression was confirmed in a tissue microarray (TMA) cohort. Furthermore, in an immunotherapy cohort of Breast cancer, patients with pathological complete response (pCR) expressed higher Proteasome activator complex subunit 2 compared with those with non-pathological complete response. In conclusion, Proteasome activator complex subunit 2 is upregulated in tumor tissues and correlated with the immuno-hot tumor immune microenvironment, which can be a novel biomarker for the recognition of tumor immune microenvironment features and immunotherapeutic response in Breast cancer.
Development of an anti-CAR antibody response in SIV-infected rhesus macaques treated with CD4-MBL CAR/CXCR5 T cells
Authors: Davey Brianna C. , Pampusch Mary S. , Cartwright Emily K. , Abdelaal Hadia M. , Rakasz Eva G. , Rendahl Aaron , Berger Edward A. , Skinner Pamela J.
Published: December 2022

T cells expressing a simian immunodeficiency (SIV)-specific chimeric antigen receptor (CAR) and the follicular homing molecule, CXCR5, were infused into antiretroviral therapy (ART) suppressed, SIV-infected rhesus macaques to assess their ability to localize to the lymphoid follicle and control the virus upon ART interruption. While the cells showed evidence of functionality, they failed to persist in the animals beyond 28 days. Development of anti-CAR antibodies could be responsible for the lack of persistence. Potential antigenic sites on the anti-SIV CAR used in these studies included domains 1 and 2 of CD4, the carbohydrate recognition domain (CRD) of mannose-binding lectin (MBL), and an extracellular domain of the costimulatory molecule, CD28, along with short linker sequences. Using a flow cytometry based assay and target cells expressing the CAR/CXCR5 construct, we examined the serum of the CD4-MBL CAR/CXCR5-T cell treated animals to determine that the animals had developed an anti-CAR antibody response after infusion. Binding sites for the anti-CAR antibodies were identified by using alternative CARs transduced into target cells and by preincubation of the target cells with a CD4 blocking antibody. All of the treated animals developed antibodies in their serum that bound to CD4-MBL CAR/CXCR5 T cells and the majority were capable of inducing an ADCC response. The CD4 antibody-blocking assay suggests that the dominant immunogenic components of this CAR are the CD4 domains with a possible additional site of the CD28 domain with its linker. This study shows that an anti-drug antibody (ADA) response can occur even when using self-proteins, likely due to novel epitopes created by abridged self-proteins and/or the self-domain of the CAR connection to a small non-self linker. While in our study, there was no statistically significant correlation between the ADA response and the persistence of the CD4-MBL CAR/CXCR5-T cells in rhesus macaques, these findings suggest that the development of an ADA response could impact the long-term persistence of self-based CAR immunotherapies.
Proteogenomic identification of Hepatitis B virus (HBV) genotype-specific HLA-I restricted peptides from HBV-positive patient liver tissues
Authors: Srivastava Mayank , Copin Richard , Choy Augustine , Zhou Anbo , Olsen Olav , Wolf Sarah , Shah Darshit , Rye-Weller Anna , Chen Lisa , Chan Newton , Coppola Angel , Lanza Kathryn , Negron Nicole , Ni Min , Atwal Gurinder S. , Kyratsous Christos A. , Olson William , Salzler Robert
Published: December 2022

The presentation of virus-derived peptides by HLA class I molecules on the surface of an infected cell and the recognition of these HLA-peptide complexes by, and subsequent activation of, CD8+ cytotoxic T cells provides an important mechanism for immune protection against viruses. Recent advances in proteogenomics have allowed researchers to discover a growing number of unique HLA-restricted viral peptides, resulting in a rapidly expanding repertoire of targets for immunotherapeutics (i.e. bispecific antibodies, engineered T-cell receptors (TCRs), chimeric antigen receptor T-cells (CAR-Ts)) to infected tissues. However, genomic variability between viral strains, such as Hepatitis-B virus (HBV), in combination with differences in patient HLA alleles, make it difficult to develop therapeutics against these targets. To address this challenge, we developed a novel proteogenomics approach for generating patient-specific databases that enable the identification of viral peptides based on the viral transcriptomes sequenced from individual patient liver samples. We also utilized DNA sequencing of patient samples to identify HLA genotypes and assist in target selection. Liver samples from 48 HBV infected patients, primarily from Asia, were examined to reconstruct patient-specific HBV genomes, identify regions within the human chromosomes targeted by HBV integrations and obtain a comprehensive view of HBV peptide epitopes using our HLA class-I (HLA-I) immunopeptidomics discovery platform. Two previously reported HLA associated HBV-derived peptides, HLA-A02 binder FLLTRILTI (S194-202) from the large surface antigen and HLA-A11 binder STLPETTVVRR (C141-151) from the capsid protein were validated by our discovery platform, but both were detected at very low frequencies. In addition, we identified and validated, using heavy peptide analogues, novel strain-specific HBV-HLA associated peptides, such as GSLPQEHIVQK (P606-616) and variants. Overall, our novel approach can guide the development of bispecific antibody, TCR-T, or CAR-T based therapeutics for the treatment of HBV-related HCC and inform vaccine development.