bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Efficacy and Safety of Paliperidone 6-Month Formulation: An Open-Label 2-Year Extension of a 1-Year Double-Blind Study in Adult Participants With Schizophrenia
Authors: Najarian Dean , Turkoz Ibrahim , Knight R Karl , Galderisi Silvana , Lamaison Hector F , Zalitacz Piotr , Aravind Suresh , Richarz Ute 
Published: July 2023

Abstract

Background
Paliperidone palmitate 6-month (PP6M) demonstrated noninferiority to paliperidone palmitate 3-month in preventing relapse in patients with schizophrenia in a phase 3 double-blind (DB) study (NCT03345342). Here, we report long-term efficacy and safety results from a 2-year single-arm, open-label extension (OLE; NCT04072575) of this DB study.

Methods
Participants who completed the DB study without relapse were enrolled and followed-up every 3 months up to 2 years. Participants received 4 PP6M gluteal injections (700/1000 mg eq.) at baseline, 6-month, 12-month, and 18-month visits. Efficacy endpoints included assessment of relapse, Positive and Negative Syndrome Scale total score, Personal and Social Performance score, and Clinical Global Impression-Severity scale change from baseline. Safety was assessed by treatment-emergent adverse events (TEAEs), physical examinations, and laboratory tests.

Results
Of 178 participants enrolled, 154 (86.5%) completed the OLE (mean age: 40.4 years, men: 70.8%; mean duration of PP6M exposure during OLE: 682.1 days). Overall, 7/178 (3.9%) participants relapsed between 20 and 703 days after enrolment. Mean (SD) changes from baseline to endpoint were as follows: Positive and Negative Syndrome Scale total score, 0.7 (8.22); Clinical Global Impression-Severity, 0.0 (0.51); and Personal and Social Performance Scale, 0.5 (7.47). Overall, 111/178 participants (62.4%) reported ≥1 TEAE; most common (&gt;5%) TEAEs were headache (13.5%) and increased blood prolactin/hyperprolactinemia (18.0%); 8/178 (4.5%) participants experienced serious TEAEs, and 6/178 (3.4%) participants withdrew due to TEAEs. No deaths were reported.

Conclusions
The relapse rate observed with PP6M during the 2-year OLE was low (3.9%). Clinical and functional improvements demonstrated in the DB study were maintained during OLE, and no new safety concerns were identified.

Trial registration
ClinicalTrials.gov Identifier: NCT04072575; EudraCT number: 2018-004532-30.
Superficial non-ampullary duodenal epithelial tumors now: endoscopic diagnosis and therapy
Authors: Hirose Takashi , Kato Motohiko , Hatta Waku , Abe Seiichiro , Takizawa Kohei , Yano Tomonori 
Published: July 2023

Abstract
With the recent increase in the frequency of duodenal tumor detection, significant progress has been made in endoscopic diagnosis and treatment. Although the first guidelines were issued in Japan, patient treatment varies widely among institutions. There is a need for improving the quality of endoscopic diagnosis and more curative and safer treatments. Biopsy is the standard diagnostic method; however, the diagnostic accuracy of endoscopic biopsy is not so high. Therefore, the differentiation of superficial non-ampullary duodenal epithelial tumors from non-neoplastic lesions is being developed. The incidence of lymph node and distant metastases of duodenal epithelial tumors is extremely rare in intramucosal carcinomas, and they are considered good candidates for endoscopic treatment if the technical difficulties can be resolved. Adverse events associated with endoscopic treatment are greatly reduced at advanced facilities through novel resection and closure methods, and further improvements are expected in the future. Clarifying the risk of metastatic recurrence may lead to the development of more appropriate treatments and curative resection criteria.
Safety and efficacy of venetoclax for acute myeloid leukaemia in real-world clinical practice
Authors: Fukumoto Ami , Narita Kentaro , Ikeda Daisuke , Uesugi Yuka , Tabata Rikako , Miura Daisuke , Takeuchi Masami , Matsue Kosei 
Published: July 2023

Abstract
Venetoclax combined with low-intensity chemotherapy has led to longer survival and higher remission rates in patients with untreated acute myeloid leukaemia who are ineligible for intensive chemotherapy. We reviewed 41 newly diagnosed and relapse/refractory acute myeloid leukaemia patients who received venetoclax at our institute. Complete remission or complete remission with incomplete recovery was achieved in 73.1% of patients. A total of 95.1% of patients discontinued venetoclax, mainly because of severe cytopenia, disease progression and haematopoietic stem cell transplantation. The median number of courses of venetoclax was 2. In all, 92.6% of the patients experienced grade ≥ 3 neutropenia. The median overall survival was 287 days. Venetoclax dose reduction resulted in better continuity of treatment with fewer complications. In conclusion, venetoclax and low-intensity chemotherapy led to high remission rates, but survival was restrained because of the large number of venetoclax discontinuations. Dose reduction of venetoclax may mitigate cytopenia while maintaining efficacy.
DNA-PK is activated by SIRT2 deacetylation to promote DNA double-strand break repair by non-homologous end joining
Authors: Head PamelaSara E , Kapoor-Vazirani Priya , Nagaraju Ganji P , Zhang Hui , Rath Sandip K , Luong Nho C , Haji-Seyed-Javadi Ramona , Sesay Fatmata , Wang Shi-Ya , Duong Duc M , Daddacha Waaqo , Minten Elizabeth V , Song Boying , Danelia Diana , Liu Xu , Li Shuyi , Ortlund Eric A , Seyfried Nicholas T , Smalley David M , Wang Ya , Deng Xingming , Dynan William S , El-Rayes Bassel , Davis Anthony J , Yu David S 
Published: July 2023

Abstract
DNA-dependent protein kinase (DNA-PK) plays a critical role in non-homologous end joining (NHEJ), the predominant pathway that repairs DNA double-strand breaks (DSB) in response to ionizing radiation (IR) to govern genome integrity. The interaction of the catalytic subunit of DNA-PK (DNA-PKcs) with the Ku70/Ku80 heterodimer on DSBs leads to DNA-PK activation; however, it is not known if upstream signaling events govern this activation. Here, we reveal a regulatory step governing DNA-PK activation by SIRT2 deacetylation, which facilitates DNA-PKcs localization to DSBs and interaction with Ku, thereby promoting DSB repair by NHEJ. SIRT2 deacetylase activity governs cellular resistance to DSB-inducing agents and promotes NHEJ. SIRT2 furthermore interacts with and deacetylates DNA-PKcs in response to IR. SIRT2 deacetylase activity facilitates DNA-PKcs interaction with Ku and localization to DSBs and promotes DNA-PK activation and phosphorylation of downstream NHEJ substrates. Moreover, targeting SIRT2 with AGK2, a SIRT2-specific inhibitor, augments the efficacy of IR in cancer cells and tumors. Our findings define a regulatory step for DNA-PK activation by SIRT2-mediated deacetylation, elucidating a critical upstream signaling event initiating the repair of DSBs by NHEJ. Furthermore, our data suggest that SIRT2 inhibition may be a promising rationale-driven therapeutic strategy for increasing the effectiveness of radiation therapy.
Dimerization of an umbravirus RNA genome activates subgenomic mRNA transcription
Authors: Chkuaseli Tamari , White K Andrew 
Published: July 2023

Abstract
Many eukaryotic RNA viruses transcribe subgenomic (sg) mRNAs during infections to control expression of a subset of viral genes. Such transcriptional events are commonly regulated by local or long-range intragenomic interactions that form higher-order RNA structures within these viral genomes. In contrast, here we report that an umbravirus activates sg mRNA transcription via base pair-mediated dimerization of its plus-strand RNA genome. Compelling in vivo and in vitro evidence demonstrate that this viral genome dimerizes via a kissing-loop interaction involving an RNA stem-loop structure located just upstream from its transcriptional initiation site. Both specific and non-specific features of the palindromic kissing-loop complex were found to contribute to transcriptional activation. Structural and mechanistic aspects of the process in umbraviruses are discussed and compared with genome dimerization events in other RNA viruses. Notably, probable dimer-promoting RNA stem-loop structures were also identified in a diverse group of umbra-like viruses, suggesting broader utilization of this unconventional transcriptional strategy.
Structural underpinnings of mutation rate variations in the human genome
Authors: Liu Zian , Samee Md Abul Hassan 
Published: July 2023

Abstract
Single nucleotide mutation rates have critical implications for human evolution and genetic diseases. Importantly, the rates vary substantially across the genome and the principles underlying such variations remain poorly understood. A recent model explained much of this variation by considering higher-order nucleotide interactions in the 7-mer sequence context around mutated nucleotides. This model's success implicates a connection between DNA shape and mutation rates. DNA shape, i.e. structural properties like helical twist and tilt, is known to capture interactions between nucleotides within a local context. Thus, we hypothesized that changes in DNA shape features at and around mutated positions can explain mutation rate variations in the human genome. Indeed, DNA shape-based models of mutation rates showed similar or improved performance over current nucleotide sequence-based models. These models accurately characterized mutation hotspots in the human genome and revealed the shape features whose interactions underlie mutation rate variations. DNA shape also impacts mutation rates within putative functional regions like transcription factor binding sites where we find a strong association between DNA shape and position-specific mutation rates. This work demonstrates the structural underpinnings of nucleotide mutations in the human genome and lays the groundwork for future models of genetic variations to incorporate DNA shape.
Human TRMT2A methylates tRNA and contributes to translation fidelity
Authors: Witzenberger Monika , Burczyk Sandra , Settele David , Mayer Wieland , Welp Luisa M , Heiss Matthias , Wagner Mirko , Monecke Thomas , Janowski Robert , Carell Thomas , Urlaub Henning , Hauck Stefanie M , Voigt Aaron , Niessing Dierk 
Published: July 2023

Abstract
5-Methyluridine (m5U) is one of the most abundant RNA modifications found in cytosolic tRNA. tRNA methyltransferase 2 homolog A (hTRMT2A) is the dedicated mammalian enzyme for m5U formation at tRNA position 54. However, its RNA binding specificity and functional role in the cell are not well understood. Here we dissected structural and sequence requirements for binding and methylation of its RNA targets. Specificity of tRNA modification by hTRMT2A is achieved by a combination of modest binding preference and presence of a uridine in position 54 of tRNAs. Mutational analysis together with cross-linking experiments identified a large hTRMT2A–tRNA binding surface. Furthermore, complementing hTRMT2A interactome studies revealed that hTRMT2A interacts with proteins involved in RNA biogenesis. Finally, we addressed the question of the importance of hTRMT2A function by showing that its knockdown reduces translation fidelity. These findings extend the role of hTRMT2A beyond tRNA modification towards a role in translation.
Cucumber abscisic acid 8′-hydroxylase Csyf2 regulates yellow flesh by modulating carotenoid biosynthesis
Authors: Wang Xueting , Jin Boyan , Yan Wenjing , Wang Jiaxi , Xu Jun , Cai Congxi , Qi Xiaohua , Xu Qiang , Yang Xiaodong , Xu Xuewen , Chen Xuehao 
Published: July 2023

Abstract
Cucumber (Cucumis sativus L.) flesh is typically colorless or pale green. Flesh with yellow or orange pigment, determined mainly by carotenoid content and composition, is mostly found in semi-wild Xishuangbanna cucumber, which has a very narrow genetic background. Here, we identified a spontaneous cucumber mutant with yellow flesh (yf-343), which accumulated more β-cryptoxanthin and less lutein than regular cultivated European glasshouse-type cucumbers. Genetic analysis revealed that the yellow flesh phenotype was controlled by a single recessive gene. Through fine mapping and gene sequencing, we identified the candidate gene C. sativus yellow flesh 2 (Csyf2), encoding an abscisic acid (ABA) 8′-hydroxylase. Overexpression and RNAi-silencing of Csyf2 in cucumber hairy roots produced lower and higher ABA contents than in non-transgenic controls, respectively. Further, RNA-seq analysis suggested that genes related to ABA signal transduction were differentially expressed in fruit flesh between yf-343 and its wild type, BY, with white flesh. The carotenoid biosynthesis pathway was specifically enriched in fruit flesh at 30 days after pollination when yf-343 fruit flesh turns yellow. Our findings highlight a promising target for gene editing to increase carotenoid content, expanding our genetic resources for pigmented cucumber flesh breeding for improving the nutritional quality of cucumber.
The extracellular matrix of green algae
Authors: Domozych David S , LoRicco Josephine G 
Published: July 2023

AbstractGreen algae display a wide range of extracellular matrix (ECM) components that include various types of cell walls (CW), scales, crystalline glycoprotein coverings, hydrophobic compounds, and complex gels or mucilage. Recently, new information derived from genomic/transcriptomic screening, advanced biochemical analyses, immunocytochemical studies, and ecophysiology has significantly enhanced and refined our understanding of the green algal ECM. In the later diverging charophyte group of green algae, the CW and other ECM components provide insight into the evolution of plants and the ways the ECM modulates during environmental stress. Chlorophytes produce diverse ECM components, many of which have been exploited for various uses in medicine, food, and biofuel production. This review highlights major advances in ECM studies of green algae.
Transcription factors TgbHLH95 and TgbZIP44 cotarget terpene biosynthesis geneTgGPPSinTorreya grandisnuts
Authors: Zhang Zuying , Tao Liu , Gao Lingling , Gao Yadi , Suo Jinwei , Yu Weiyu , Hu Yuanyuan , Wei Chunyan , Farag Mohamed A , Wu Jiasheng , Song Lili 
Published: July 2023

AbstractTerpenes are volatile compounds responsible for aroma and the postharvest quality of commercially important xiangfei (Torreya grandis) nuts, and there is interest in understanding the regulation of their biosynthesis. Here, a transcriptomics analysis of xiangfei nuts after harvest identified 156 genes associated with the terpenoid metabolic pathway. A geranyl diphosphate (GPP) synthase (TgGPPS) involved in production of the monoterpene precursor GPP was targeted for functional characterization, and its transcript levels positively correlated with terpene levels. Furthermore, transient overexpression of TgGPPS in tobacco (Nicotiana tabacum) leaves or tomato (Solanum lycopersicum) fruit led to monoterpene accumulation. Analysis of differentially expressed transcription factors identified one basic helix-loop-helix protein (TgbHLH95) and one basic leucine zipper protein (TgbZIP44) as potential TgGPPS regulators. TgbHLH95 showed significant transactivation of the TgGPPS promoter, and its transient overexpression in tobacco leaves led to monoterpene accumulation, whereas TgbZIP44 directly bound to an ACGT-containing element in the TgGPPS promoter, as determined by yeast 1-hybrid test and electrophoretic mobility shift assay. Bimolecular fluorescence complementation, firefly luciferase complementation imaging, co-immunoprecipitation, and GST pull-down assays confirmed a direct protein–protein interaction between TgbHLH95 and TgbZIP44 in vivo and in vitro, and in combination these proteins induced the TgGPPS promoter up to 4.7-fold in transactivation assays. These results indicate that a TgbHLH95/TgbZIP44 complex activates the TgGPPS promoter and upregulates terpene biosynthesis in xiangfei nuts after harvest, thereby contributing to its aroma.
Inferring human neutral genetic variation from craniodental phenotypes
Authors: Rathmann Hannes , Perretti Silvia , Porcu Valentina , Hanihara Tsunehiko , Scott G Richard , Irish Joel D , Reyes-Centeno Hugo , Ghirotto Silvia , Harvati Katerina 
Published: July 2023

Abstract
There is a growing consensus that global patterns of modern human cranial and dental variation are shaped largely by neutral evolutionary processes, suggesting that craniodental features can be used as reliable proxies for inferring population structure and history in bioarchaeological, forensic, and paleoanthropological contexts. However, there is disagreement on whether certain types of data preserve a neutral signature to a greater degree than others. Here, we address this unresolved question and systematically test the relative neutrality of four standard metric and nonmetric craniodental data types employing an extensive computational genotype–phenotype comparison across modern populations from around the world. Our computation draws on the largest existing data sets currently available, while accounting for geographically structured environmental variation, population sampling uncertainty, disparate numbers of phenotypic variables, and stochastic variation inherent to a neutral model of evolution. Our results reveal that the four data types differentially capture neutral genomic variation, with highest signals preserved in dental nonmetric and cranial metric data, followed by cranial nonmetric and dental metric data. Importantly, we demonstrate that combining all four data types together maximizes the neutral genetic signal compared with using them separately, even with a limited number of phenotypic variables. We hypothesize that this reflects a lower level of genetic integration through pleiotropy between, compared to within, the four data types, effectively forming four different modules associated with relatively independent sets of loci. Therefore, we recommend that future craniodental investigations adopt holistic combined data approaches, allowing for more robust inferences about underlying neutral genetic variation.
ببناء الجاهزية: دراسة حالة للعوامل المهنية التي تؤثر على مستويات ‘السعادة’ لضباط شرطة أبو ظبي
Authors: الكعبي فيصل 
Published: July 2023

الملخصيخوض المجتمع الشرطي والأمني على الصعيد العالمي سباقًا مع الزمن لتطوير استراتيجيات لتحسين رفاهية الصحة العقلية في أوساط المهنة للمهنيين، من خلال المجالات المساهمة المتعددة التي تدعم رفاهية ضباط الشرطة، على سبيل المثال: الأطباء وعلماء النفس والمهنيون الإداريون والموجهون والمدربون والمستشارون، فإنّ فهم العوامل المساهمة من التجربة بالإضافة إلى تصور وإدراك ضباط الشرطة يُعدُّ مجالًا مهمًا في الأبحاث. (بيكر وآخرون، 2020. ديشين وآخرون، 2018. بوربا وديمو، 2019) كان الهدف من الدراسة الواردة في هذه المقالة هو تقييم تأثير عوامل العمل المتصلة بالمكافآت التنظيمية، وخصائص الوظائف، والعوامل المتصلة بالعمل في مؤسسات الخدمات العامة بشأن تصور الضباط للسعادة. تم توزيع استبيان على ضباط الشرطة في أبو ظبي ، مع إجراء تحليل استنتاجي لفحص العلاقات بين عوامل العمل ومستويات سعادة الضباط. حيث حددت النتائج تصور الموظفين للمكافآت التنظيمية، والتحكم في الوظيفة، وأهمية المهمة، وتكرار التعليقات أو الملاحظات، والرغبة في مساعدة الآخرين كأسباب أولية للعمل في الشرطة، والفرص المتاحة لمساعدة الآخرين في المجتمع كلها تنبئ بسعادة الشرطة. تناقش هذه المقالة – تحديدًا - تصور الموظفين للمكافآت في العمل وخصائص الوظيفة كمحددات للسعادة،حيث تساهم النتائج في تطوير استجابة تنظيمية مستقبلية لتعزيز رفاهية الضباط، والأهم من ذلك أنها تُعلِم بناء الجاهزية أمام اضطرابات الصحة العقلية لضباط الشرطة.
تحديد عوامل التمكين والمعوقات لإدارة المعرفة في المؤسسة الشرطية. دراسة حالة لشرطة أبو ظبي
Authors: الظنحاني محمد , النقبي شماء 
Published: July 2023

الملخص
قد تكون إدارة المعرفة المستخلصة وفعاليتها حافزاً محتملاً لتحقيق أهداف المشروع لتحقيق النجاح والسرعة الأمثل، أو قد تكون : سببًا رئيسيًا لفشل المشروع عندما تتم إدارة المعرفة بشكل غير كافٍ. تطرقت الأبحاث العلمية الحديثة إلى عدم تسهيل تطبيق آليات إدارة المعرفة في جميع مراحل المشروع بسبب الوضع المؤقت للمشروعات وكذلك أوجه القصور في تطبيق مفهوم المساءلة بين المتخصصين. تتناول هذه الورقة عنصرًاواحدًا من مشروع بحثي أوسع يتم تنفيذه مع شرطة أبوظبي لتحديد العوامل التمكينية والعوائق التي تحول دون إدارة المعرفة في مشاريع الشرطة. كان البحث نوعيًا بطبيعته وركز بشكل مباشر على معالجة آليات وطرق دمج المعرفة الإدارية لتحسين نجاح المشروع وتطوير قدرة رأس المال البشري في العمل الشرطي. حددت نتائج البحث تسعة عوامل تمكينية تدعم إدارة المعرفة الناجحة في المشاريع الشرطية: سياسة لإدارة المعرفة، والقيادة المؤسسية لدعم التواصل المفتوح والتحفيز، تسليط الضوء على قيمة إدارة المعرفة، ربط محتوى إدارة المعرفة بتوصيف الوظائف، إنشاء قنوات محددة للتواصل مع المعنيين في المشروع، الموارد التكنولوجية الكافية، أنظمة الاتصال لإدارة المعرفة بين الفرق في مواقع منفصلة، تمكين التفاعل الاجتماعي لتسهيل عملية إدارة المعرفة في العمليات اليومية، تطبيق عمليات التقييم والقياس في استخدام الشبكات الاجتماعية لإدارة المعرفة.
A fast emergency department triage score based on mobility, mental status and oxygen saturation compared with the emergency severity index: a prospective cohort study
Authors: Riedel H B , Espejo T , Bingisser R , Kellett J , Nickel C H 
Published: July 2023

Summary

Background
Waiting for triage in overburdened emergency departments (ED) has become an increasing problem, which endangers patients. A fast triage system to rapidly identify low-acuity patients should divert care and resources to more urgent cases.

Aim
The objective of this study was to compare the performance of the Kitovu Hospital fast triage (KFT) score with the Emergency Severity Index (ESI), using mortality and hospital admission as proxies for the patients’ acuity.

Design
This is a prospective observational study of consecutive patients presenting to a Swiss academic ED.

Methods
Patients were prospectively triaged into one of five ESI strata and retrospectively assessed by the KFT score, which awards one point each for altered mental status, impaired mobility and oxygen saturation &lt;94%.

Results
The KFT score had a lower discrimination than the ESI for hospital admission, but a higher discrimination for mortality from 24 h to 1 year after ED presentation. A total of 5544 (67%) patients were assigned to the lowest acuity by the KFT score compared with 2374 (28.7%) by the ESI; there was no significant difference in the 24-h mortality of patients who were deemed low acuity by either score.

Conclusion
Compared to the ESI, the KFT score identifies more than twice as many patients at low risk of early death. Therefore, this score might help to identify patients who could be managed through alternative pathways. This may be particularly helpful in situations of ED crowding and access block.
Technology and the Task Content of Jobs across the Development Spectrum
Authors: Caunedo Julieta , Keller Elisa , Shin Yongseok 
Published: July 2023

Abstract
The tasks workers perform on the job are informative about the direction and the impact of technological change. We harmonize occupational task-content measures between two worker-level surveys, which separately cover developing and developed countries. Developing countries use routine-cognitive tasks and routine-manual tasks more intensively than developed countries, but less intensively use non-routine analytical tasks and non-routine interpersonal tasks. This is partly because developing countries have more workers in occupations with high routine content and fewer workers in occupations with high non-routine content. More importantly, a given occupation has more routine content and less non-routine content in developing countries than in developed countries. Since 2006, occupations with high non-routine content gained employment relative to those with high routine content in most countries, regardless of their income level or initial task intensity, indicating the global reaches of the technological change that reduces the demand for occupations with high routine content.