bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver-specific lncRNA FAM99A may be a tumor suppressor and promising prognostic biomarker in hepatocellular carcinoma
Authors: Mo Meile , Ma Xiaoyun , Luo Yihuan , Tan Chao , Liu Bihu , Tang Peng , Liao Qian , Liu Shun , Yu Hongping , Huang Dongping , Zeng Xiaoyun , Qiu Xiaoqiang 
Published: October 2022

Abstract
Background
Increasing evidence shows that liver-specific long non-coding RNAs (lncRNAs) play important roles in the development of hepatocellular carcinoma (HCC). We identified a novel liver-specific lncRNA, FAM99A, and examined its clinical significance and biological functions in HCC.

Methods
The expression level and clinical value of FAM99A in HCC were examined using The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) databases, and were further verified using quantitative real-time polymerase chain reaction (qRT–PCR) in our HCC cohort. Univariate and multivariate Cox proportional hazards regression models were also applied to identify independent prognostic indicators for HCC patients. Cell counting kit-8, colony formation, and Transwell assays were performed to evaluate the effects of FAM99A on the proliferation, migration, and invasion abilities of HCC cells in vitro. A subcutaneous xenograft tumor model was implemented to determine the effect of FAM99A on the tumor growth of HCC cells in vivo. RNA pull-down and mass spectrometry assays were performed to reveal the potential molecular mechanisms of FAM99A in HCC.

Results
The three public online databases and qRT–PCR data showed that FAM99A was frequently downregulated in HCC tissues and inversely correlated with microvascular invasion and advanced histological grade of HCC patients. Kaplan–Meier survival analysis indicated that decreased FAM99A was significantly associated with poor overall survival of HCC patients based on TCGA database (P = 0.040), ICGC data portal (P < 0.001), and our HCC cohort (P = 0.010). A multivariate Cox proportional hazards regression model based on our HCC cohort suggested that FAM99A was an independent prognostic factor of overall survival for HCC patients (hazard ratio: 0.425, P = 0.039). Upregulation of FAM99A suppressed the proliferation, colony formation, migration, and invasion capacities of HCC cells in vitro, and knockdown of FAM99A had the opposite effects. A subcutaneous xenograft tumor model demonstrated that overexpression of FAM99A significantly inhibited the tumor growth of HCC cells in vivo. Seven tumor-related proteins (PCBP1, SRSF5, SRSF6, YBX1, IGF2BP2, HNRNPK, and HNRNPL) were recognized as possible FAM99A-binding proteins by the RNA pull-down and mass spectrometry assays.

Conclusion
Our results suggest that FAM99A exerts cancer-inhibiting effects on HCC progression, and it may be a promising prognostic indicator for HCC patients.
Frequency, proportion of PF-ILD, and prognostic factors in patients with acute exacerbation of ILD related to systemic autoimmune diseases
Authors: Enomoto Noriyuki , Naoi Hyogo , Mochizuka Yasutaka , Isayama Takuya , Tanaka Yuko , Fukada Atsuki , Aono Yuya , Katsumata Mineo , Yasui Hideki , Mori Kazutaka , Karayama Masato , Hozumi Hironao , Suzuki Yuzo , Furuhashi Kazuki , Fujisawa Tomoyuki , Inui Naoki , Nakamura Yutaro , Suda Takafumi 
Published: October 2022

Abstract
Background
Acute exacerbation (AE) of systemic autoimmune disease-related interstitial lung diseases (SAID-ILD) is less common than AE of idiopathic pulmonary fibrosis (IPF) and the details of AE-SAID-ILD have not been elucidated, but the prognosis is similarly devastating. This study was undertaken to determine the incidences of AE-ILD in each SAID and to elucidate the proportion of progressive fibrosing (PF)-ILD in AE-SAID-ILD.

Methods
We retrospectively analysed data for patients with SAID-ILD who were diagnosed and observed at our hospital between 1999 and 2020.

Results
Two hundred and thirty-two patients with SAID-ILD were enrolled, with a mean observation period of 100.2 months. AE-SAID-ILD was found in 25 patients (10.78%), mainly in patients with RA (17 patients, 68%) and elderly male patients with a smoking history. The overall incidence of AE-SAID-ILD was 1.29%/person-year, and the incidence for each SAID was as follows: RA 2.193, microscopic polyarteritis (MPA) 3.203, systemic sclerosis (SSc) 2.277, primary Sjögren syndrome 0.426, and polymyositis/dermatomyositis 0.222. The incidence of AE of RA/MPA/SSc-ILD was significantly higher than that of other AE-SAID-ILD (p < 0.001). Five of 25 patients (20%) fulfilled the criteria for PF-ILD. The 90-day survival rate was 48.0%, and a higher neutrophil count at AE (HR 13.27, 95%CI 2.447–246, p = 0.001) and early commencement of long-duration direct haemoperfusion with a polymyxin B-immobilised fibre column (HR 0.105, 95%CI 0.005–0.858, p = 0.035) were significant prognostic factors.

Conclusions
The incidence of AE-SAID-ILD was significantly higher in patients with RA, MPA, or SSc than in patients with other SAID. Furthermore, even in patients with AE-SAID-ILD, the proportion of PF-ILD just before AE was not high (20%).
Implementation of a soft grading system for chemistry in a Moodle plugin
Authors: Plyer Louis , Marcou Gilles , Perves Céline , Schurhammer Rachel , Varnek Alexandre 
Published: October 2022

AbstractWe report a novel approach for grading chemical structure drawings for remote teaching, integrated into the Moodle platform. Typically, existing online platforms use a binary grading system, which often fails to give a nuanced evaluation of the answers given by the students. Therefore, such platforms are unevenly adapted to different disciplines. This is particularly true in the case of chemical structures, where most questions simply cannot be evaluated on a true/false basis. Specifically, a strict comparison of candidate and expected chemical structures is not sufficient when some tolerance is deemed acceptable. To overcome this limitation, we have developed a grading workflow based on the pairwise similarity score of two considered chemical structures. This workflow is implemented as a Moodle plugin, using the Chemdoodle engine for drawing structures and communicating with a REST server to compute the similarity score using molecular descriptors. The plugin (https://github.com/Laboratoire-de-Chemoinformatique/moodle-qtype_molsimilarity) is easily adaptable to any academic user; both embedding and similarity measures can be configured.
Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment
Authors: Rosario Spencer R. , Smith Randall J. , Patnaik Santosh K. , Liu Song , Barbi Joseph , Yendamuri Sai 
Published: October 2022

AbstractContrary to the “obesity paradox,” which arises from retrospective studies relying on body mass index to define obesity, epidemiologic evidence suggests central or visceral obesity is associated with a higher risk for the development of lung cancer. About 60% of individuals at high risk for developing lung cancer or those already with early-stage disease are either overweight or obese. Findings from resected patient tumors and mouse lung tumor models show obesity dampens immune activity in the tumor microenvironment (TME) encouraging disease progression. In line with this, we have observed a marked, obesity-specific enhancement in the presence and phenotype of immunosuppressive regulatory T (Treg) cells in murine tumors as well as the airways of both humans and mice. Leveraging direct metabolomic measurements and robust inferred analyses from RNA-sequencing data, we here demonstrate for the first time that visceral adiposity alters the lung microenvironment via dysregulated acetyl-CoA metabolism in a direction that facilitates immune suppression and lung carcinogenesis.
Agricultural land use shapes dispersal in white-tailed deer (Odocoileus virginianus)
Authors: Gilbertson Marie L. J. , Ketz Alison C. , Hunsaker Matthew , Jarosinski Dana , Ellarson Wesley , Walsh Daniel P. , Storm Daniel J. , Turner Wendy C. 
Published: October 2022

Abstract
Background
Dispersal is a fundamental process to animal population dynamics and gene flow. In white-tailed deer (WTD; Odocoileus virginianus), dispersal also presents an increasingly relevant risk for the spread of infectious diseases. Across their wide range, WTD dispersal is believed to be driven by a suite of landscape and host behavioral factors, but these can vary by region, season, and sex. Our objectives were to (1) identify dispersal events in Wisconsin WTD and determine drivers of dispersal rates and distances, and (2) determine how landscape features (e.g., rivers, roads) structure deer dispersal paths.

Methods
We developed an algorithmic approach to detect dispersal events from GPS collar data for 590 juvenile, yearling, and adult WTD. We used statistical models to identify host and landscape drivers of dispersal rates and distances, including the role of agricultural land use, the traversability of the landscape, and potential interactions between deer. We then performed a step selection analysis to determine how landscape features such as agricultural land use, elevation, rivers, and roads affected deer dispersal paths.

Results
Dispersal predominantly occurred in juvenile males, of which 64.2% dispersed, with dispersal events uncommon in other sex and age classes. Juvenile male dispersal probability was positively associated with the proportion of the natal range that was classified as agricultural land use, but only during the spring. Dispersal distances were typically short (median 5.77 km, range: 1.3–68.3 km), especially in the fall. Further, dispersal distances were positively associated with agricultural land use in potential dispersal paths but negatively associated with the number of proximate deer in the natal range. Lastly, we found that, during dispersal, juvenile males typically avoided agricultural land use but selected for areas near rivers and streams.

Conclusion
Land use—particularly agricultural—was a key driver of dispersal rates, distances, and paths in Wisconsin WTD. In addition, our results support the importance of deer social environments in shaping dispersal behavior. Our findings reinforce knowledge of dispersal ecology in WTD and how landscape factors—including major rivers, roads, and land-use patterns—structure host gene flow and potential pathogen transmission.
Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic NF2 Mutations
Authors: Brastianos Priscilla K. , Twohy Erin L. , Gerstner Elizabeth R. , Kaufmann Timothy J. , Iafrate A. John , Lennerz Jochen , Jeyapalan Suriya , Piccioni David E. , Monga Varun , Fadul Camilo E. , Schiff David , Taylor Jennie W. , Chowdhary Sajeel A. , Bettegowda Chetan , Ansstas George , De La Fuente Macarena , Anderson Mark D. , Shonka Nicole , Damek Denise , Carrillo Jose , Kunschner-Ronan Lara J. , Chaudhary Rekha , Jaeckle Kurt A. , Senecal Francis M. , Kaley Thomas , Morrison Tara , Thomas Alissa A. , Welch Mary R. , Iwamoto Fabio , Cachia David , Cohen Adam L. , Vora Shivangi , Knopp Michael , Dunn Ian F. , Kumthekar Priya , Sarkaria Jann , Geyer Susan , Carrero Xiomara W. , Martinez-Lage Maria , Cahill Daniel P. , Brown Paul D. , Giannini Caterina , Santagata Sandro , Barker Frederick G. , Galanis Evanthia 
Published: October 2022

PURPOSE Patients with progressive or recurrent meningiomas have limited systemic therapy options. Focal adhesion kinase (FAK) inhibition has a synthetic lethal relationship with NF2 loss. Given the predominance of NF2 mutations in meningiomas, we evaluated the efficacy of GSK2256098, a FAK inhibitor, as part of the first genomically driven phase II study in recurrent or progressive grade 1-3 meningiomas. PATIENTS AND METHODS Eligible patients whose tumors screened positively for NF2 mutations were treated with GSK2256098, 750 mg orally twice daily, until progressive disease. Efficacy was evaluated using two coprimary end points: progression-free survival at 6 months (PFS6) and response rate by Macdonald criteria, where PFS6 was evaluated separately within grade-based subgroups: grade 1 versus 2/3 meningiomas. Per study design, the FAK inhibitor would be considered promising in this patient population if either end point met the corresponding decision criteria for efficacy. RESULTS Of 322 patients screened for all mutation cohorts of the study, 36 eligible and evaluable patients with NF2 mutations were enrolled and treated: 12 grade 1 and 24 grade 2/3 patients. Across all grades, one patient had a partial response and 24 had stable disease as their best response to treatment. In grade 1 patients, the observed PFS6 rate was 83% (10/12 patients; 95% CI, 52 to 98). In grade 2/3 patients, the observed PFS6 rate was 33% (8/24 patients; 95% CI, 16 to 55). The study met the PFS6 efficacy end point both for the grade 1 and the grade 2/3 cohorts. Treatment was well tolerated; seven patients had a maximum grade 3 adverse event that was at least possibly related to treatment with no grade 4 or 5 events. CONCLUSION GSK2256098 was well tolerated and resulted in an improved PFS6 rate in patients with recurrent or progressive NF2-mutated meningiomas, compared with historical controls. The criteria for promising activity were met, and FAK inhibition warrants further evaluation for this patient population.
Community social responsibility of continued and appropriate use of silver amalgam as dental restorative material in southern India: A cross-sectional study
Authors: Vasthare Ramprasad , Ballal Nidambur Vasudev , Nayak Prajna P , Kamath Pujan , Singla Nishu , Hegde Thrisha 
Published: October 2022

Background: For more than 150 years, dental amalgam (DA) has been popular as a dental restorative material. Yet, many organisations oppose its use due to perceived toxicity and environmental concerns. Hence, this study aimed to explore the continued use of DA from a South Indian dental practitioners’ perspective. Methods: This cross-sectional study was conducted among fifty-two private and public dental practitioners of Udupi district in Southern India. A self‑administered questionnaire was distributed, that involved assessment of their preferences, continuation of use and concerns of using DA as a restorative material. Percentage contribution of each variable was calculated. Preferences for continuation of use of silver amalgam based upon the age, experience and mercury toxicity as a risk factor were analysed using Students-t test and Chi-square test. Results: The majority of dentists were satisfied (87%) with the results of the DA, found minimal failures (96%) and found DA more economical (89%). More than half (54%) of the participants reported that they would not continue the use of DA owing to mercury toxicity and environmental concerns. Dentists with higher age and longer clinical experience preferred continuation of DA. Conclusions: In spite of satisfaction with DA for its minimal failure, longevity and affordability, the authors found that a majority of practitioners did not prefer its continued usage. This highlights their concerns over mercury toxicity and soft tissue lesions and accentuates their community social responsibility. There is also an urgent need to educate dentists on mercury hygiene, mercury waste management and disposal.
Nadzieja skowana niepewnością. Wokół myśli Lwa Szestowa
Authors: Prokopski Jacek Aleksander 
Published: October 2022

NADZIEJA SKOWANA NIEPEWNOŚCIĄ
WOKÓŁ MYŚLI LWA SZESTOWA

W artykule, odwołując się do egzystencjalnych przemyśleń Lwa Szestowa nad ludzkim losem, Bogiem i przeznaczeniem świata, nie zapominając o rosyjskiej duszy filozofa, starano się uwyraźnić problem ludzkiej nadziei. Nadziei, która odnajdywana jest w prawdach opartych na sprzecznościach. Nie są to bowiem abstrakcyjne, wypolerowane prawdy rozumu, lecz prawdy egzystencjalne, rządzące się szczególnymi prawidłami. Mianowicie takimi, które spoczywają poza obszarem pewności naszej egzystencji. W tym sensie oczywiste jest, iż myśliciel żąda od filozofii rzeczy niemożliwej, by językiem nauki orzekała o tym, co filozofią nie jest. Szestow zostaje więc oceniony jako ten, który „myśli poza logiką i filozofią”, co sytuuje go w realnej opozycji do cechu akademickich filozofów. Dla nich to, jako zdeklarowanych racjonalistów, Szestowowskie „myślenie poza myśleniem” oznaczało brak pewności i zagubienie. Paradoksalnie właśnie tam, w „chaosie” braku spekulatywnych rozwiązań, w przerażającej egzystencji Hioba i jemu podobnych, Szestow odnajduje drogę nadziei na odnalezienie prawdy wiecznej, prowadzącej do wrót zbawienia.

Słowa kluczowe:
Nadzieja, niepewność, tajemnica, paradoks, prawda, filozofia, poznanie, system, egzystencja, Bóg, racjonalizm, irracjonalizm, możliwe, niemożliwe, metafizyka, idealizm, materializm.
The feedback loop of METTL14 and USP38 regulates cell migration, invasion and EMT as well as metastasis in bladder cancer
Authors: Huang Ji , Zhou Weimin , Hao Chao , He Qiuming , Tu Xinhua 
Published: October 2022

Background
Bladder cancer (BCa) is one of the most prevalent malignancies globally. Previous study has reported the inhibitory effect of methyltransferase-like 14 (METTL14) on BCa tumorigenesis, but its role in the cell migration, invasion and epithelial–mesenchymal transition (EMT) in BCa remains unknown.

Materials and methods
Quantitative real-time PCR (RT-qPCR) and western blot were applied to measure RNA and protein expression respectively. Cell migration, invasion and EMT were evaluated by wound healing, Transwell, and immunofluorescence (IF) assays as well as western blot of EMT-related proteins. In vivo experiments were performed to analyze metastasis of BCa. Mechanism investigation was also conducted to study METTL14-mediated regulation of BCa progression.

Results
METTL14 overexpression prohibits BCa cell migration, invasion in vitro and tumor metastasis in vivo. METTL14 stabilizes USP38 mRNA by inducing N6-methyladenosine (m6A) modification and enhances USP38 mRNA stability in YTHDF2-dependent manner. METTL14 represses BCa cell migration, invasion and EMT via USP38. Additionally, miR-3165 inhibits METTL14 expression to promote BCa progression.

Conclusions
Our study demonstrated that METTL14 suppresses BCa progression and forms a feedback loop with USP38. In addition, miR-3165 down-regulates METTL14 expression to promote BCa progression. The findings may provide novel insight into the underlying mechanism of METTL14 in BCa progression.
Patient-reported outcomes evaluation and assessment of facilitators and barriers to physical activity in the Transplantoux aerobic exercise intervention
Authors: Masschelein Evi , De Smet Stefan , Denhaerynck Kris , Ceulemans Laurens J. , Monbaliu Diethard , De Geest Sabina 
Published: October 2022

Background
Transplantoux’s MVT exercise intervention prepares organ transplant recipients to cycle or hike up France’s Mont Ventoux. We aimed to assess (i) MVT’s effects on patient-reported outcomes (PROs) and (ii) perceived barriers and facilitators to physical activity.

Methods
Using a hybrid design, a convenience sample of transplant recipients participating in MVT (n = 47 cycling (TxCYC); n = 18 hiking (TxHIK)), matched control transplant recipients (TxCON, n = 213), and healthy MVT participants (HCON, n = 91) completed surveys to assess physical activity (IPAQ), health-related quality of life (HRQOL; SF-36 and EuroQol VAS), mental health (GHQ-12), and depressive symptomatology, anxiety, and stress (DASS-21) at baseline, then after 3, 6 (Mont Ventoux climb), 9, and 12 months. TxCYC and TxHIK participated in a 6-month intervention of individualized home-based cycling/hiking exercise and a series of supervised group training sessions. Barriers and facilitators to physical activity (Barriers and Motivators Questionnaire) were measured at 12 months.

Results
Regarding PROs, except for reducing TxHIK stress levels, MVT induced no substantial intervention effects. For both TxCYC and TxHIK, between-group comparisons at baseline showed that physical activity, HRQOL, mental health, depressive symptomatology and stress were similar to those of HCON. In contrast, compared to TxCYC, TxHIK, and HCON, physical activity, HRQOL and mental health were lower in TxCON. TxCON also reported greater barriers, lower facilitators, and different priority rankings concerning physical activity barriers and facilitators.

Conclusion
Barely any of the PROs assessed in the present study responded to Transplantoux’s MVT exercise intervention. TxCON reported distinct and unfavorable profiles regarding PROs and barriers and facilitators to physical activity. These findings can assist tailored physical activity intervention development.

Trial registration
Clinical trial notation: The study was approved by the University Hospitals Leuven’s Institutional Review Board (B322201523602).
Work time allocation at primary health care level in two regions of Albania
Authors: Muho Altiona , Peshkatari Altina , Wyss Kaspar 
Published: October 2022

IntroductionAlthough well-performing workforce is essential to equitable and efficient health service delivery, few countries have systematically addressed performance improvements. How health workers use their work time and what tasks they accomplish is here an important starting point. Therefore, a time motion study was conducted to assess the work time allocation patterns of primary health care doctors and nurses in two regions of Albania.MethodsWe used observation tool to record the time allocation along eight predefined main categories of activities. Conditional to presence at work, 48 health workers were continuously observed in early 2020 before start of the Covid-19 pandemic over five consecutive working days.ResultsThe observed health workers spent 40.7% of their overall working time unproductively (36.8% on waiting for patients and 3.9% on breaks), 25.3% on service provision to users, 18.7% on administrative activities, 12.7% on outreach activities, 1.6% on continuous medical education and 1% on meetings. The study found variations in work time allocation patterns across cadres, with nurses spending more time unproductively, on administrative activities and on outreach and less on all other activities than doctors. Further, the work time allocation patterns were similar between urban and rural settings, except for nurses in rural settings spending less time than those in urban settings on administrative work.ConclusionThis study found that primary health care workers in Albania devote a substantial amount of work time to unproductive, service provision to users and administrative activities. Consequently, there is possibility for productivity, respectively efficiency gains in how health workers use their time.