bluuebunny/crossref_metadata_2025_split huggingface dataset:
Marine-derived microbes and molecules for drug discovery
Authors: Tanaka Yoshimasa , Nishikawa Megumi , Kamisaki Kaho , Hachiya Saki , Nakamura Moeka , Kuwazuru Takahiro , Tanimura Susumu , Soyano Kiyoshi , Takeda Kohsuke 
Published: June 2022

AbstractIncreasing attention has been paid to marine-derived biomolecules as sources of therapeutics for autoimmune diseases. Nagasaki Prefecture has many islands and is surrounded by seas, straits, gulfs, bays, and coves, giving it the second longest coastline in Japan after Hokkaido. We have collected more than 20,000 marine microbes and have been preparing an original marine microbial extract library, which contains small and mid-size biomolecules that may penetrate cell membranes and interfere with the intracellular protein–protein interaction involved in the development of autoinflammatory diseases such as familial Mediterranean fever. In addition, we have been developing an indoor shark farming system to prepare shark nanobodies that could be developed as potential therapeutic agents for autoimmune diseases. Sharks produce heavy-chain antibodies, called immunoglobulin new antigen receptors (IgNARs), consisting of one variable domain (VNAR) and five constant domains (CNAR); of these, VNAR can recognize a variety of foreign antigens. A VNAR single domain fragment, called a nanobody, can be expressed in Escherichia coli and has the properties of an ideal therapeutic candidate for autoimmune diseases. Shark nanobodies contain complementarity-determining regions that are formed through the somatic rearrangement of variable, diversity, and joining segments, with the segment end trimming and the N- and P-additions, as found in the variable domains of mammalian antibodies. The affinity and diversity of shark nanobodies are thus expected to be comparable to those of mammalian antibodies. In addition, shark nanobodies are physically robust and can be prepared inexpensively; as such, they may lead to the development of highly specific, stable, effective, and inexpensive biotherapeutics in the future. In this review, we first summarize the history of the development of conventional small molecule drugs and monoclonal antibody therapeutics for autoimmune diseases, and then introduce our drug discovery system at Nagasaki University, including the preparation of an original marine microbial extract library and the development of shark nanobodies.
Quality of life and its predictors among patients with migraine in Qassim region, Saudi Arabia: a cross-sectional study
Authors: Almosaiteer Sarah Abdulrahman , Rabbani Unaib , Alharbi Basil Abdulrahman , Aldukhayel Abdulrhman 
Published: June 2022

AbstractBackgroundMigraine attacks can last for hours to days with severe pain which can affect the daily activities. Literature on quality of life of migraineurs is Saudi Arabia is scarce. This study aimed to assess the quality of life and its predictors among patients with migraine in Qassim region, Saudi Arabia.MethodsA cross-sectional study was conducted among patients with migraines in Qassim, Saudi Arabia. A self-administered questionnaire was distributed online among migraine patients that included; socio-demographic characteristics and an Arabic version of validated migraine-specific quality of life questionnaire (MSQ), version 2.1. Data analyses were performed in SPSS version 26.ResultsA total of 320 patients with migraines participated in the study. The most common age group was 18–25 years (36.6%) with females were dominant (60.9%). According to the results of MSQ version 2.1, the mean ± SD scores of Role Restrictive (RR), Role Preventive (RP), and Emotion Function (EF) were 67.7 ± 19.7, 68.5 ± 20.6, and 70.6 ± 22.1, respectively. Statistical tests revealed that patients who reported less frequent migraine attacks, had better scores in RR, RP, and EF, while the use of paracetamol and painkillers for the treatment of headache were associated with lower scores in RR, RP, and EF.ConclusionsThe quality of life among patients with migraines was generally moderate. Males demonstrated better QOL than females. Furthermore, patients who had less frequent migraine attacks exhibited better QOL than the others but working patients were likely to demonstrate poor QOL.
Clinical outcomes and survivorship of cementless triathlon total knee arthroplasties: a systematic review
Authors: Carlson Brian J. , Gerry Adam S. , Hassebrock Jeffrey D. , Christopher Zachary K. , Spangehl Mark J. , Bingham Joshua S. 
Published: June 2022

Abstract
Background
Over the last decade, cementless total knee arthroplasty has demonstrated improved outcomes and survivorship due to advances in technologies of implant design, manufacturing capabilities, and biomaterials. Due to increasing interest in cementless implant design for TKA, our aim was to perform a systematic review of the literature to evaluate the clinical outcomes and revision rates of the Triathlon Total Knee system over the past decade.

Methods
A systematic review of the literature was conducted following PRISMA guidelines for patients who underwent total knee arthroplasty with cementless Triathalon Total Knee System implants. Patients had a minimum of two-year follow-up and data included clinical outcome scores and survivorship data.

Results
Twenty studies were included in the final analysis. The survivability of the Stryker Triathlon TKA due to all causes was 98.7%, with an aseptic survivability of 99.2%. The overall revision incidence per 1,000 person-years was 3.4. Re-revision incidence per 1,000 person-years was 2.2 for infection, and 1.3 for aseptic loosening. The average KSS for pain was 92.2 and the average KSS for function was 82.7.

Conclusions
This systematic review demonstrated excellent clinical outcomes and survivorship at a mean time of 3.8 years. Additional research is necessary to examine the long-term success of the Stryker Triathlon TKA and the use of cementless TKAs in obese and younger populations.

Level of evidence
III.
The role of radiogenomics in the diagnosis of breast cancer: a systematic review
Authors: Darvish Leili , Bahreyni-Toossi Mohammad-Taghi , Roozbeh Nasibeh , Azimian Hosein 
Published: June 2022

Abstract
Background
One of the most common cancers diagnosed worldwide is breast cancer (BC), which is the leading cause of cancer death among women. The radiogenomics method is more accurate for managing and inhibiting this disease, which takes individual diagnosis on genes, environments, and lifestyles of each person. The present study aims to highlight the current state-of-the-art, the current role and limitations, and future directions of radiogenomics in breast cancer.

Method
This systematic review article was searched from databases such as Embase, PubMed, Web of Science, Google Scholar, Scopus, and Cochrane Library without any date or language limitations of databases. Searches were performed using Boolean OR and AND operators between the main terms and keywords of particular topic of the subject under investigation. All retrospective, prospective, cohort, and pilot studies were included, which were provided with more details about the topic. Articles such as letter to the editor, review, and short communications were excluded because of lack of information, discussions, or use of radiogenomics method on other cancers. For quality assessment of articles, STROBE checklist was used.

Result
For the systematic review, 18 articles were approved after assessing the full text of selected articles. In this review, 3614 patients with BC of selected articles were evaluated, and all radiogenomics were associated with more power in classification, differential diagnosis, and prognosis of BC. Among the various modalities to predict genomic indicators and molecular subtypes, DCE-MRI has the higher performance and finally the highest amount of AUC value (0.956) belonged to PI3K gene.

Conclusion
This review shows that radiogenomics can help with the diagnosis and treatment of breast cancer in patients. It has shown that recognizing and specifying radiogenomic phenotypes in the genomic signatures can be helpful in treatment and diagnosis of disease. The molecular methods used in these articles are limited to miRNAs expression, gene expression, Ki67 proliferation index, next-generation RNA sequencing, whole RNA sequencing, and molecular histopathology that can be completed in future studies by other methods such as exosomal miRNAs, specific proteins expression, DNA repair capacity, and other biomarkers that have prognostic and predictive value for cancer treatment response. Studies with control group and large sample size for evaluation of radiogenomics in diagnosis and treatment recommended.
Potential roles of claudin-3 and claudin-4 in ovarian cancer management
Authors: Uthayanan Leshanth , El-Bahrawy Mona 
Published: June 2022

Abstract
Background
Ovarian cancer has the highest mortality amongst all gynaecological malignancies, with around two-thirds of patients diagnosed with advanced disease due to late presentation. Furthermore, around 90% of patients develop recurrence and eventually become chemoresistant. Therefore, there is a high demand to identify biomarkers specific to this disease for screening for early detection, as well as new therapeutic targets. Tight junctions (TJs) regulate paracellular permeability and are vital in establishing epithelial cell polarity. One hallmark of tumorigenesis is the loss of TJs, with loss of cell-to-cell adhesion. Claudins are integral TJ membrane proteins, which have been found to play a critical role in maintaining the TJ’s barrier function. Furthermore, claudin-3 (CLDN3) and claudin-4 (CLDN4) are overexpressed in ovarian cancer. This article aims to explore the biological role of CLDN3 and CLDN4 and their potential in different aspects of the management of ovarian cancer.

Main body
CLDN3 and CLDN4 have been shown to be effective markers for the early detection of ovarian cancer. Whilst there is difficulty in screening for both claudins in serum, their assessment by gene expression analysis and immunohistochemical methods shows promising potential as diagnostic and prognostic biomarkers for ovarian cancer. The localisation and overexpression of claudins, such as CLDN3, have been shown to correlate with poorer survival outcomes. The added value of combining claudins with other markers such as CA125 for diagnosis has also been highlighted. Therapeutically, CLDN3 and more so CLDN4 have been shown to be effective targets of Clostridium perfringens enterotoxin (CPE). Interestingly, CPE has also been shown to resensitise chemoresistant tumours to therapy.

Conclusions
This review presents the diagnostic and prognostic potential of CLDN3 and CLDN4 and their emerging role as therapeutic targets in ovarian cancer. Clinical trials are required to validate the promising results of the in vitro and in vivo studies for CLDN3 and CLDN4, possibly adding onto current ovarian cancer management.
Malignancy risk stratification of thyroid nodules smaller than 10 mm with ACR-TIRADS, K-TIRADS, and ATA-2015 guidelines: a prospective study
Authors: Nabahati Mehrdad , Moazezi Zoleika 
Published: June 2022

Abstract
Background
Small thyroid nodules (≤ 10 mm) are common findings in thyroid ultrasonography. The first purpose of this study was to compare the performance of three guidelines in the diagnosis of malignancy for small thyroid nodules. The second aim was to find the ultrasonographic characteristics potentially associated with the risk of malignancy. This prospective cross-sectional study was performed on the patients with a diagnosis of small thyroid nodules (≤ 10 mm), who were rereferred to the radiologists for sonography and FNA. Sonographic features were recorded and scored according to the American College of Radiology-Thyroid Imaging Reporting and Data System (ACR-TIRADS), American Thyroid Association (ATA-2015), and Korean-TIRADS (K-TIRADS). Finally, FNA was conducted and cytological findings were reported.

Results
In total, 287 thyroid nodules from 256 subjects (64 men and 192 women) were finally included in the study. The accuracy of ACR-TIRADS categories TR5 and TR4/5 was 88.9% and 72.1%, respectively. This rate for ATA-2015 classes high suspicion and intermediate suspicion/high suspicion was 88.9% and 82.6%, respectively. For K-TIRADS classes 5 and 4/5, the diagnostic accuracy was 89.6% and 82.9%, respectively. Significant direct associations were found between malignancy and punctate echogenic foci (odds ratio [OR] = 6.46), hypoechogenicity (OR = 6.39), ill-defined margin (OR = 4.38), and irregular margin (OR = 7.33).

Conclusion
The differences in the strength of the three guidelines in the prediction of the malignancy should be considered by clinicians and radiologists in the management of thyroid nodules smaller than 10 mm.
Impact of breeder seed multiplication and certified quality seed distribution on rice production in India
Authors: Prasad Gogineni S. V. , Rao Chilukuri S. , Suneetha Kota , Muralidharan Kalambur , Siddiq E. A. 
Published: June 2022

Abstract
Background
The All India Coordinated Rice Improvement Project (AICRIP) organizes multi-location tests (METs) with new genotypes from breeding programs. The best performing genotypes in METs for 3–4 years are identified and notified as commercial cultivars by the Government of India (GOI) to authorize breeder seed (BS) production.

Methods
We created a database and analyzed data on BS production for 24 years (1995–96 to 2018–19) in 475 inbred and 22 F1 hybrid cultivars. Estimates were made to rank cultivars on the proportional contribution of a cultivar, quantity produced and a new BS index. Correlation and regression analyses were used to find the relationships between BS, certified quality seed distributed (CQSD), and milled rice production. We compared cultivars in BS production chain with those grown in farmers’ fields across the country as identified in the production-oriented surveys.

Results
The top ten inbred cultivars identified are Jaya (notified by GOI in 1969), Swarna, Kranthi, IR 36, Sarjoo 52, Samba Mahsuri and Pusa Basmati 1 (notified in 1980–1989), and IR 64, Vijetha and Cottondora Sannalu (notified in 1991–2000). BS production in hybrid F1 was insignificant. We detected a Pearson correlation (r = 0.806, P < 0.01) between the BS production and CQSD, and a linear relationship between the annual rice production in India and the CQSD (R2 = 0.850, P < 0.01). The rice area coverage in 2018–19 with CQSD estimated was 41%. A total of 1877 cultivars (528 notified and 1349 not notified) were found at farms in rice growing districts in India.

Conclusions
From 1995–2019, BS and CQSD together increased the annual milled rice production in step with increases in population. Diverse rice genotypes have enabled rice to endure crop constraints in fragmented landholdings spread over 43 m ha. AICRIP’s efforts have sustained availability of > 73 kg rice per capita per year (~ 40% of food grains). The process of notification, receipt of indent for BS from states, allotment and BS production, and de-notification of a cultivar by GOI need a review to ensure profits to farmers. As the 1000-seed weight varies in cultivars, it must be notified by GOI to adjust seed rate and maintain the recommended plant population at the farms. There is scope to increase the priceless BS production in cultivars to raise the country’s production further, facilitate export and ensure profits to all stakeholders.
The temporal relationships between defeat, entrapment and suicidal ideation: ecological momentary assessment study
Authors: van Ballegooijen Wouter , Littlewood Donna L. , Nielsen Emma , Kapur Nav , Gooding Patricia 
Published: June 2022

Background
Psychological models of suicidal experiences are largely based on cross-sectional or long-term prospective data with follow-up intervals typically greater than 1 year. Recent time-series analyses suggest that these models may not account for fluctuations in suicidal thinking that occur within a period of hours and/or days.

Aims
We explored whether previously posited causal relationships between defeat, entrapment and suicidal ideation accounted for temporal associations between these experiences at small time intervals from 3 to 12 h.

Method
Participants (N = 51) completed an ecological momentary assessment (EMA) study, comprising repeated assessments at semi-random time points up to six times per day for 1 week, resulting in 1852 completed questionnaires. Multilevel vector autoregression was used to calculate temporal associations between variables at different time intervals (i.e. 3 to 12 h between measurements).

Results
The results showed that entrapment severity was temporally associated with current and later suicidal ideation, consistently over these time intervals. Furthermore, entrapment had two-way temporal associations with defeat and suicidal ideation at time intervals of approximately 3 h. The residual and contemporaneous network revealed significant associations between all variables, of which the association between entrapment and defeat was the strongest.

Conclusions
Although entrapment is key in the pathways leading to suicidal ideation over time periods of months, our results suggest that entrapment may also account for the emergence of suicidal thoughts across time periods spanning a few hours.
Randomised controlled trial of the short-term effects of osmotic-release oral system methylphenidate on symptoms and behavioural outcomes in young male prisoners with attention deficit hyperactivity disorder: CIAO-II study
Authors: Asherson Philip J. , Johansson Lena , Holland Rachel , Bedding Megan , Forrester Andrew , Giannulli Laura , Ginsberg Ylva , Howitt Sheila , Kretzschmar Imogen , Lawrie Stephen M. , Marsh Craig , Kelly Caroline , Mansfield Megan , McCafferty Clare , Khan Khuram , Müller-Sedgwick Ulrich , Strang John , Williamson Grace , Wilson Lauren , Young Susan , Landau Sabine , Thomson Lindsay D. G. 
Published: June 2022

BackgroundResearch has shown that 20–30% of prisoners meet the diagnostic criteria for attention-deficit hyperactivity disorder (ADHD). Methylphenidate reduces ADHD symptoms, but effects in prisoners are uncertain because of comorbid mental health and substance use disorders.AimsTo estimate the efficacy of an osmotic-release oral system methylphenidate (OROS-methylphenidate) in reducing ADHD symptoms in young adult prisoners with ADHD.MethodWe conducted an 8-week parallel-arm, double-blind, randomised placebo-controlled trial of OROS-methylphenidate versus placebo in male prisoners (aged 16–25 years) meeting the DSM-5 criteria for ADHD. Primary outcome was ADHD symptoms at 8 weeks, using the investigator-rated Connors Adult ADHD Rating Scale (CAARS-O). Thirteen secondary outcomes were measured, including emotional dysregulation, mind wandering, violent attitudes, mental health symptoms, and prison officer and educational staff ratings of behaviour and aggression.ResultsIn the OROS-methylphenidate arm, mean CAARS-O score at 8 weeks was estimated to be reduced by 0.57 points relative to the placebo arm (95% CI −2.41 to 3.56), and non-significant. The responder rate, defined as a 20% reduction in CAARS-O score, was 48.3% for the OROS-methylphenidate arm and 47.9% for the placebo arm. No statistically significant trial arm differences were detected for any of the secondary outcomes. Mean final titrated dose was 53.8 mg in the OROS-methylphenidate arm.ConclusionsADHD symptoms did not respond to OROS-methylphenidate in young adult prisoners. The findings do not support routine treatment with OROS-methylphenidate in this population. Further research is needed to evaluate effects of higher average dosing and adherence to treatment, multi-modal treatments and preventative interventions in the community.
Multiomics analysis of pediatric solid tumors within the INFORM precision oncology study: From functional drug profiling to biomarker identification.
Authors: ElHarouni Dina , Peterziel Heike , Schramm Kathrin , Milde Till , Oppermann Sina , Oehme Ina , Witt Olaf , Schlesner Matthias , Jäger Natalie 
Published: June 2022

10036 Background: Within the INFORM (INdividualized Therapy FOr Relapsed Malignancies in Childhood) registry over 1200 childhood malignancies were molecularly profiled using next generation sequencing to identify therapeutic targets. Nevertheless, high evidence targets were only detected in 5% of cases and only 50% of the patients were identified with druggable pathways, while the remaining cases lacked druggable alterations. Thus, an ex-vivo functional drug response profiling platform for pediatric solid tumors has been established within the INFORM program to identify novel biomarkers and unravel molecular mechanisms associated with drug response profiles for clinical translation. Methods: Solid tumors from 97 paediatric patients were screened against a library of 76 drugs. A quality control classification decision tree was designed to select the samples for further analysis. Whole exome sequencing, low-coverage whole genome sequencing, and RNA-seq were used to analyze the molecular profiles of the samples. Molecular features were filtered to retain oncogenic and druggable events. Five data feature views (mutations, mRNA, gene fusions, CNVs, and drug responses) were used to train a Multi-Omics Factor Analysis (MOFA) model to identify prominent latent factors. Results: 81 samples passed the quality control inclusion criteria of which 76 samples had available omics data profiles. Quantitative drug profiling measurements were reported using the selective asymmetric drug sensitivity score.The multi-omics analysis captured five entity-specific omics signatures of Ewing sarcoma, Wilms tumor, BCOR sarcoma, neuroblastoma and ependymoma. Moreover, the analysis revealed sensitivity to navitoclax in neuroblastoma samples with PHOX2B-GATA3 overexpression, and an association between MEK inhibitor sensitivity and an expression signature in Wilms tumors. Conclusions: The combination of functional drug and multi-omics profiling enabled the identification of novel biomarkers for drug sensitivities in pediatric solid tumors. As we continue to expand the number of patient samples evaluated with our drug sensitivity platform, this dataset will provide insights for novel drug targets, and could unravel key molecular events and mechanisms acting towards personalized therapies.