bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome architecture of the three main lineages of agrobacteria
Authors: Waldburger Lucas , Thompson Mitchell G. , Weisberg Alexandra J. , Lee Namil , Chang Jeff H. , Keasling Jay D. , Shih Patrick M. 
Published: July 2023

ABSTRACT

Agrobacteria are a diverse, polyphyletic group of prokaryotes with multipartite genomes capable of transferring DNA into the genomes of host plants, making them an essential tool in plant biotechnology. Despite their utility in plant transformation, genome-wide transcriptional regulation is not well understood across the three main lineages of agrobacteria. Transcription start sites (TSSs) are a necessary component of gene expression and regulation. In this study, we used differential RNA-seq and a TSS identification algorithm optimized on manually annotated TSS, then validated with existing TSS to identify thousands of TSS with nucleotide resolution for representatives of each lineage. We extend upon the 356 TSSs previously reported in
Agrobacterium fabrum
C58 by identifying 1,916 TSSs. In addition, we completed genomes and phenotyping of
Rhizobium rhizogenes
C16/80 and
Allorhizobium vitis
T60/94, identifying 2,650 and 2,432 TSSs, respectively. Parameter optimization was crucial for an accurate, high-resolution view of genome and transcriptional dynamics, highlighting the importance of algorithm optimization in genome-wide TSS identification and genomics at large. The optimized algorithm reduced the number of TSSs identified internal and antisense to the coding sequence on average by 90.5% and 91.9%, respectively. Comparison of TSS conservation between orthologs of the three lineages revealed differences in cell cycle regulation of
ctrA
as well as divergence of transcriptional regulation of chemotaxis-related genes when grown in conditions that simulate the plant environment. These results provide a framework to elucidate the mechanistic basis and evolution of pathology across the three main lineages of agrobacteria.

IMPORTANCE
Transcription start sites (TSSs) are fundamental for understanding gene expression and regulation. Agrobacteria, a group of prokaryotes with the ability to transfer DNA into the genomes of host plants, are widely used in plant biotechnology. However, the genome-wide transcriptional regulation of agrobacteria is not well understood, especially in less-studied lineages. Differential RNA-seq and an optimized algorithm enabled identification of thousands of TSSs with nucleotide resolution for representatives of each lineage. The results of this study provide a framework for elucidating the mechanistic basis and evolution of pathology across the three main lineages of agrobacteria. The optimized algorithm also highlights the importance of parameter optimization in genome-wide TSS identification and genomics at large.
Amber photobiomodulation versus tranexamic acid for the treatment of melasma: protocol for a double-blind, randomised controlled trial
Authors: Galache Thais Rodrigues , Galache Marcelo , Sena Michelle Mota , Pavani Christiane 
Published: July 2023

IntroductionPhotobiomodulation (PBM) has been suggested as an alternative treatment for melasma.In vitrostudies have shown PBM with amber light inhibits the tyrosinase enzyme, induces autophagy and reduces the melanin content, but randomised controlled clinical trials are still needed. This study aims to evaluate the efficacy of amber PBM (590 nm) in the treatment of melasma compared with liposomal tranexamic acid.Methods and analysisThis study is a controlled, randomised, double-blind, non-inferiority trial. This study will be performed in two centres (Universidade Nove de Julho Facility, Campus Vergueiro, and Galache Odontology Clinic, São Caetano do Sul, both in São Paulo State, Brazil). The sample (54 participants) will be divided into two groups in a 1:1 ratio; one group will receive active PBM and a placebo cosmetic and the other will receiveshamPBM and liposomal tranexamic acid. Women presenting facial melasma, aged 35–50 years, with skin phototypes II–IV, will be eligible for inclusion. Women who use oral contraceptives, intrauterine devices, hormone replacement or photosensitive drugs, those with autoimmune disease and those who have undergone facial treatments in the last 3 months will be excluded from the study. The participants will receive PBM weekly for 12 weeks and will use the cosmetic two times per day at home during this period. The severity of melasma will be evaluated through the Melasma Area and Severity Index (MASI) as the primary outcome; pigmentation of the epidermis evaluated by corneomelametry, the photographic records, the global diagnosis of the face and the quality-of-life questionnaire (Brazilian Portuguese version of the Melasma Quality of Life Questionnaire) will assessed as secondary outcomes. All assessments will be made before starting the study (week 0), mid-study at 6 weeks and at the completion of treatment (week 12). MASI will also be evaluated during follow-up (weeks 16 and 20). The data will be analysed based on the intention-to-treat analysis using a generalised mixed model, and α <0.05 will be considered statistically significant.Ethics and disseminationThe protocol was approved by the Research Ethics Committee of Universidade Nove de Julho (5 332 384). All participants will fill out the patient informed consent form. The results obtained in this trial will be presented at conferences and submitted for publication.Trial registration numberClinicalTrials.gov Registry (NCT05326997).
Causal discovery approach with reinforcement learning for risk factors of type II diabetes mellitus
Authors: Gao Xiu-E. , Hu Jian-Gang , Chen Bo , Wang Yun-Ming , zhou Sheng-Bin 
Published: July 2023

Abstract
Background
Statistical correlation analysis is currently the most typically used approach for investigating the risk factors of type 2 diabetes mellitus (T2DM). However, this approach does not readily reveal the causal relationships between risk factors and rarely describes the causal relationships visually.

Results
Considering the superiority of reinforcement learning in prediction, a causal discovery approach with reinforcement learning for T2DM risk factors is proposed herein. First, a reinforcement learning model is constructed for T2DM risk factors. Second, the process involved in the causal discovery method for T2DM risk factors is detailed. Finally, several experiments are designed based on diabetes datasets and used to verify the proposed approach.

Conclusions
The experimental results show that the proposed approach improves the accuracy of causality mining between T2DM risk factors and provides new evidence to researchers engaged in T2DM prevention and treatment research.
Analysis of female pre-clinical students’ readiness, academic performance and satisfaction in online learning: an assessment of quality for curriculum revision and future implementation
Authors: Ganesh Kavitha , Rashid Najwa Abdur , Hasnaoui Raja El , Assiri Rasha , Cordero Mary Anne W. 
Published: July 2023

AbstractBackgroundThe acceptance of online courses by medical and dental students, especially during the coronavirus disease 2019 crisis, is substantial, as reported in various studies. However, the unfavourable online learning experiences of the students during the pandemic were also highlighted. As the teaching-learning process is returning to the “new normal,“ it is necessary to identify online learning domains implemented during the pandemic crisis that may be applied in pre-clinical courses in the future.MethodsA validated Student Online Learning Readiness questionnaire assessed pre-clinical students’ online learning competence. Students’ academic performance in face-to-face post-pandemic was compared with their performance in online settings during the pandemic crisis. Students’ satisfaction with online learning was evaluated using a self-made survey questionnaire. Descriptive statistics, the t-test, and multiple regression analysis were used to analyze the data gathered with a p-value ≤ 0.05 considered statistically significant.ResultsExcept for social skills with classmates and groupmates, in which 47.5% of respondents indicated unreadiness, most students were prepared for online learning. Theory-wise, online learners outperformed traditional learners, but the difference was insignificant. In contrast, students’ practical skills in face-to-face modality are significantly higher (p = 0.029). Students rated their satisfaction with online learning higher for interactions with instructors and staff and lower for interactions with classmates and group mates and skill acquisition.ConclusionProviding high-quality pre-clinical online teaching was achieved for theoretical components but not practical skills acquisition. Students’ social engagement with peers is one of the key elements crucial to online learning success. Academic leaders and curriculum developers must recognize potential gaps as they transition to online learning.
New paradigms in research on Dirofilaria immitis
Authors: Geary Timothy G. 
Published: July 2023

Abstract
Background
Since the advent of ivermectin (along with melarsomine and doxycycline), heartworm has come to be viewed as a solved problem in veterinary medicine, diminishing investment into non-clinical research on Dirofilaria immitis. However, heartworm infections continue to pose problems for practitioners and their patients and seem to be increasing in frequency and geographic distribution. Resistance to preventative therapies (macrocyclic lactones) complicates the picture. The use of chemotherapy for other kinds of pathogens has benefitted enormously from research into the basic biology of the pathogen and on the host-pathogen interface. A lack of basic information on heartworms as parasites and how they interact with permissive and non-permissive hosts greatly limits the ability to discover new ways to prevent and treat heartworm disease. Recent advances in technical platforms will help overcome the intrinsic barriers that hamper research on D. immitis, most notably, the need for experimentally infected dogs to maintain the life cycle and provide material for experiments. Impressive achievements in the development of laboratory animal models for D. immitis will enhance efforts to discover new drugs for prevention or treatment, to characterize new diagnostic biomarkers and to identify key parasite-derived molecules that are essential for survival in permissive hosts, providing a rational basis for vaccine discovery. A ‘genomics toolbox’ for D. immitis could enable unprecedented insight into the negotiations between host and parasite that enable survival in a permissive host. The more we know about the pathogen and how it manipulates its host, the better able we will be to protect companion animals far into the future.

Graphical Abstract
Anti-carbamylated protein antibodies in systemic sclerosis
Authors: Liem Sophie I. E. , Hoekstra E. M. , Levarht E. W. Nivine , Dorjee Annemarie L. , Scherer Hans U. , Toes René E. M. , Huizinga Tom W. J. , de Vries-Bouwstra Jeska K. , Fehres Cynthia M. 
Published: July 2023

Abstract
Background
To investigate the presence of different isotypes of anti-carbamylated protein (CarP) antibodies in systemic sclerosis (SSc) patients and its association with skin involvement.

Methods
Sera of 194 SSc patients from the Leiden CCISS cohort, fulfilling ACR/EULAR 2013 criteria and a clinical diagnosis of SSc, 83 patients with other connective tissue diseases/Raynaud’s Phenomenon, 24 rheumatoid arthritis patients and 98 age and sex-matched healthy controls were tested for the presence of anti-CarP IgG, IgA and IgM, determined by ELISA. Clinical characteristics, that were evaluated in SSc patients, included age, anti-topoisomerase antibodies (ATA), anti-centromere antibodies (ACA) and modified Rodnan Skin Score (mRSS).

Results
The SSc patients were 55 (SD:13) years and 155 (80%) were female. Forty-four (23%) patients tested positive for ATA, and 80 (42%) ACA. The median mRSS was 2 (range: 0; 47).
Prevalence of anti-CarP IgG was higher in SSc patients than in healthy controls (8% vs 3%, p = 0.007. Prevalence of anti-CarP IgA and IgM and levels of anti-CarP isotypes were comparable between SSc patients and healthy controls.
Fifteen (8%) SSc patients tested positive for anti-CarP IgG, 16 (8%) for anti-CarP IgA, and 36 (19%) for anti-CarP IgM. There were no significant correlations between age and levels of anti-CarP isotypes. No correlation between anti-CarP IgG levels and mRSS was found (r = 0.141, p = 0.049), nor for anti-CarP IgM and IgA levels. Anti-CarP IgA levels were higher in ATA compared to ACA positive SSc patients (ATA: 616 aU/ml [359; 1103]; ACA: 424 aU/ml [300; 673], p = 0.015).

Conclusion
SSc patients can test positive for Anti-CarP IgG, IgA and IgM. We do not observe a relevant clinical association between anti-CarP antibody response and skin involvement in SSc.
Correlation between anti-hypertensive drugs and disease progression among moderate, severe, and critically ill COVID-19 patients in the second referral hospital in Surabaya: A retrospective cohort study
Authors: Suryantoro Satriyo Dwi , Thaha Mochammad , Hayati Mutiara Rizky , Yusuf Mochammad , Pikir Budi Susetyo , Susilo Hendri 
Published: July 2023

Background: Hypertension, as the comorbidity accompanying COVID-19, is related to angiotensin-converting enzyme 2 receptor (ACE-2R) and endothelial dysregulation which have an important role in blood pressure regulation. Other anti-hypertensive agents are believed to trigger the hyperinflammation process. We aimed to figure out the association between the use of anti-hypertensive drugs and the disease progression of COVID-19 patients. Methods: This study is an observational cohort study among COVID-19 adult patients from moderate to critically ill admitted to Universitas Airlangga Hospital (UAH) Surabaya with history of hypertension and receiving anti-hypertensive drugs. Results: Patients receiving beta blockers only had a longer length of stay than angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ACEI/ARB) or calcium channel blockers alone (17, 13.36, and 13.73 respectively), had the higher rate of intensive care unit (ICU) admission than ACEi/ARB (p 0.04), and had the highest mortality rate (54.55%). There were no significant differences in length of stay, ICU admission, mortality rate, and days of death among the single, double, and triple anti-hypertensive groups. The mortality rate in groups taking ACEi/ARB was lower than other combination. Conclusions: Hypertension can increase the severity of COVID-19. The use of ACEI/ARBs in ACE-2 receptor regulation which is thought to aggravate the condition of COVID-19 patients has not yet been proven. This is consistent with findings in other anti-hypertensive groups.
Translation and cross-cultural adaptation of the Persian version of inflammatory bowel disease-fatigue (IBD-F) self-assessment questionnaire
Authors: Hatamnejad Mohammad Reza , Shirvani Marzieh , Pourhoseingholi Mohamad Amin , Balaii Hedieh , Shahrokh Shabnam , Asadzadeh Aghdaei Hamid , Koolaeian Amirhosein , Cheraghpour Makan 
Published: July 2023

Background
This study appraises the psychometrics properties of the Inflammatory bowel disease-fatigue (IBD-F) Persian version questionnaire.

Methods
The original IBD-F questionnaire was translated into the Persian version in a standard forward-back manner. The validation was performed through the face, content, and construct validity. Fifteen experts scored each item’s necessity on an ordinal Likert scale of three; then, the content validity ratio was calculated using the Lawshe formula. Eight judges from pre-defined panel rated each item on an ordinal 4-point Likert scale concerning its relevancy, clarity, and simplicity for individual-CVI calculation. The mean individual-CVI was considered as the Scale-CVI for each domain. Twenty lay experts (selected from the target population) were asked to express their opinion on each item’s importance by scoring on a 5-point Likert scale; subsequently, face validity was determined by the impact score formula. The questions that had minimum values of CVR, CVI, and impact score were retained in the final version of the questionnaire for reliability evaluation. Construct validity was evaluated via Confirmatory Factor Analysis. Internal consistency and test-retest reliability were checked using Cronbach’s α and intraclass correlation coefficients (ICC). Fifty-four patients recruited based on inclusion and exclusion criteria to participate in the reliability analysis.

Results
All the questions received the qualified values of CVR (exceeding 0.49 points) and impact score (more than 1.5 points) and were retained in the questionnaire; however, revisions were made for questions with a CVI 0.7–0.9 for clarity and simplicity. The result demonstrated relative goodness CFA and proper internal consistency, as Cronbach’s α coefficient was 0.964 for the test (0.845 and 0.963 for the first and second part of the questionnaire, respectively (and 0.888 for the re-test (0.793 and 0.876 for the first and second section of the questionnaire, respectively). The ICC values between test and re-test for the first and second part and the whole questionnaire were obtained as 0.904, 0.922, and 0.921, respectively.

Conclusion
The Persian version of the IBD-F questionnaire was valid and reliable; thus, an appropriate scale was deemed to measure fatigue (severity, frequency, and impact on daily activities).
Recommendations for the study of monoclonal gammopathies in the clinical laboratory. A consensus of the Spanish Society of Laboratory Medicine and the Spanish Society of Hematology and Hemotherapy. Part I: Update on laboratory tests for the study of monoclonal gammopathies
Authors: Cárdenas María C. , García-Sanz Ramón , Puig Noemí , Pérez-Surribas David , Flores-Montero Juan , Ortiz-Espejo María , de la Rubia Javier , Cruz-Iglesias Elena 
Published: July 2023

Abstract
Monoclonal gammopathies (MG) are characterized by the proliferation of plasma cells that produce identical abnormal immunoglobulins (intact or some of their subunits). This abnormal immunoglobulin component is called monoclonal protein (M-protein), and is considered a biomarker of proliferative activity. The identification, characterization and measurement of M-protein is essential for the management of MG. We conducted a systematic review of the different tests and measurement methods used in the clinical laboratory for the study of M-protein in serum and urine, the biochemistry and hematology tests necessary for clinical evaluation, and studies in bone marrow, peripheral blood and other tissues. This review included literature published between 2009 and 2022. The paper discusses the main methodological characteristics and limitations, as well as the purpose and clinical value of the different tests used in the diagnosis, prognosis, monitoring and assessment of treatment response in MG. Included are methods for the study of M-protein, namely electrophoresis, measurement of immunoglobulin levels, serum free light chains, immunoglobulin heavy chain/light chain pairs, and mass spectrometry, and for the bone marrow examination, morphological analysis, cytogenetics, molecular techniques, and multiparameter flow cytometry.
Projetos terapêuticos singulares em saúde mental no Brasil: revisão de literatura
Authors: Borges Dimitri Xavier , Avelar Kátia Eliane Santos 
Published: July 2023

The objective of this study was to analyze the studies carried out in Brazil that related treatment and follow-up in mental health with singular therapeutic local practices throughout the Psychosocial Care Network (RAPS). Methodology: articles indexed in the databases National Library of Medicine – Pubmed and Scientific Electronic Library Online - Scielo, from 2010 in Portuguese and English. Four articles were selected, two were developed in the Southeast region of Brazil, a region with a high Human Development Index (HDI), one in the South region and the other in the Brazilian Northeast. Results: The results showed the lack of studies and actions in the area of mental health involving therapeutic and singular practices, as advocated by the United Nations Organization and the Psychiatric Reform in Brazil. Conclusion: this theme has been little investigated in the country, suggesting the encouragement of research and local practices in mental health and the promotion of public policies, considering the need for constant and growing actions due to the importance of the uniqueness of the treatment necessary for patients with mental disorders and their different possible techniques of biopsychosocial intervention.
PROMIS Physical Function and Pain Interference Scores Correlate with the Lower Extremity Toronto Extremity Salvage Score
Authors: Jin Julie , Hong Zachery , Rhea Lee , McDonald Douglas J. , O’Keefe Regis J. , Cipriano Cara A. 
Published: July 2023

Background:
The Toronto Extremity Salvage Score (TESS) and the National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) are both utilized to measure patient-reported outcomes in adults with musculoskeletal oncologic conditions. However, the relationship between them has not been studied. We sought to describe a link between Lower Extremity (LE) TESS and PROMIS Physical Function (PF) scores, as well as between LE TESS and Pain Interference (PI) scores, to develop a method for converting scores between TESS and PROMIS and to examine whether TESS and PROMIS captured differences in pain and function between clinically relevant subgroups in our population.

Methods:
Our study population consisted of 125 adult patients who underwent surgical treatment of a lower-extremity musculoskeletal tumor at a single sarcoma center between December 2015 and October 2018. The LE TESS questionnaire was administered to patients via paper and the PROMIS PF and PI were administered via iPad at a preoperative appointment. The relationship between LE TESS and PROMIS measures was analyzed with use of generalized linear modeling. Subgroup analyses were performed with a 2-tailed t test or 1-way analysis of variance.

Results:
PROMIS PF had a very strong positive correlation with LE TESS (r = 0.83) and was related through the following equation: PROMIS PF = 0.00294 × (LE TESS)2 + 22.6. PROMIS PI had a strong negative correlation with LE TESS (r = –0.77) and was related through the following equation: PROMIS PI = −0.00259 × (LE TESS)2 + 73.8. PROMIS PF and PI performed similarly to LE TESS across multiple patient subgroups and captured the expected differences between subgroups.

Conclusions:
LE TESS and PROMIS PF appeared to measure similar information in patients with an orthopaedic oncologic condition. Moreover, PROMIS PI scores were strongly correlated with functional disability as measured with the LE TESS. Understanding the relationship between TESS and PROMIS will allow the comparison and combination of data for both clinical and research purposes.

Level of Evidence:
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.