bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kangyi Qiangshen Gong exercise prescription for pulmonary function and quality of life in patients recovered from COVID-19: a study protocol for a randomized controlled trial
Authors: Guo Guangxin , Xu Xiruo , Yin Wong Yu , Zhang Kunyu , Hui Jacelyn Pang Min , Yee Janice Hiew Yuen , Heng Bryan Chung Qi , Qin Yuan , Yao Fei , Fang Min 
Published: October 2022

Abstract
Background
Since early 2022, patients with 2019 novel coronavirus (COVID-19) infection have increased rapidly in Shanghai, China. Nevertheless, there is no widely used unified rehabilitation treatment available for discharged patients with post-infection sequelae such as dyspnea, depression, and fatigue. To promote the rehabilitation of discharged patients, our team formulated Kangyi Qiangshen Gong exercise prescription on the basis of traditional Chinese medicine rehabilitation exercises (TCMRE). We designed a randomized controlled trial to evaluate the efficacy of rehabilitation and advantages of KQG for discharged patients with post-COVID-19 syndrome.

Methods/design
This is a parallel-design, two-arm, analyst assessor-blinded, randomized controlled trial. In total, 60 discharged patients with COVID-19 sequelae, aged from 20 to 80 years will be recruited and randomly assigned to the World Health Organization instructed breathing techniques (BT) group and the Kangyi Qiangshen Gong exercise prescription (KQG) group at a ratio of 1:1. The patients in the BT group will perform breathing techniques exercise, and the patients in the KQG group will perform KQG exercise. Both groups will perform exercises twice a day for 3 months. The primary outcome will be measured with the Modified Medical Research Council Dyspnea Scale, and the secondary outcomes will include the Modified Borg Scale, Fatigue Scale-14, Patient Health Questionnaire-9 Scale, Pittsburgh Sleep Quality Index, and the Respiratory Symptoms Scale. Clinical scales will be assessed at three points (pre-exercise, 3 months post-exercise, and 3 months follow-up). Adverse events will be recorded for safety assessment.

Discussion
This trial will serve high-quality evidence of the value of KQG for treating discharged patients with COVID-19 in rehabilitation period.

Trial registration
Chinese Clinical Trial Registry ChiCTR2200059504. Registered on 03 May 2022.

Dissemination
The results will be published in peer-reviewed journals and disseminated through the study’s website, and conferences.
Improving VAE based molecular representations for compound property prediction
Authors: Tevosyan Ani , Khondkaryan Lusine , Khachatrian Hrant , Tadevosyan Gohar , Apresyan Lilit , Babayan Nelly , Stopper Helga , Navoyan Zaven 
Published: October 2022

AbstractCollecting labeled data for many important tasks in chemoinformatics is time consuming and requires expensive experiments. In recent years, machine learning has been used to learn rich representations of molecules using large scale unlabeled molecular datasets and transfer the knowledge to solve the more challenging tasks with limited datasets. Variational autoencoders are one of the tools that have been proposed to perform the transfer for both chemical property prediction and molecular generation tasks. In this work we propose a simple method to improve chemical property prediction performance of machine learning models by incorporating additional information on correlated molecular descriptors in the representations learned by variational autoencoders. We verify the method on three property prediction tasks. We explore the impact of the number of incorporated descriptors, correlation between the descriptors and the target properties, sizes of the datasets etc. Finally, we show the relation between the performance of property prediction models and the distance between property prediction dataset and the larger unlabeled dataset in the representation space.
An analytical assessment of industrial sector innovative management in the context of digitalization
Authors: Sherimova Nurzhanat , Isabekov Baurzhan , Alkeev Miras , Yermekova Zhanna , Ostryanina Tatyana 
Published: October 2022

AbstractThe accumulated potential in digitalization suggests the need to create a new paradigm for managing scientific-innovative and production-technological processes, which is reflected in the author’s article. In these conditions, there is the problem of developing a mechanism for innovative management of the industrial sector of the economy. The study aims to analyze statistical and analytical data of modern industrial sector management in the context of digitalization. By analytical, comparative, and statistical analysis of international innovation management approaches, according to the rating of the global innovation index 2020/2021 and business activity of technological leaders in Asia, North America, and Europe, the authors developed a methodological approach to improve the mechanism for implementing innovative management in industrial sector. The mechanism includes such core elements: state industrial policy—purposes of industrial development—decision on innovative management implementation—development of mechanism to implement innovative decision—expected short- and long-term results based on the traceability of innovation and the overall economic context from a global perspective. The study results can be applied for implementing innovative management in industrial sector and developing industrial policies.
Extremes of mixed-use architecture: a spatial analysis of vertical functional mix in Dhaka
Authors: Khan Fatema Meher , Pafka Elek , Dovey Kim 
Published: October 2022

AbstractThe concept of mixed-use is now well-established as an urban design and planning principle that adds to the vitality, walkability and productivity of the city at neighbourhood scale. There is much less research on the dense and complex vertical mix of functions within buildings. This paper investigates the extremes of informal vertical mixing of functions within buildings in Dhaka, where commercial and retail functions often penetrate to upper floors and where access routes are often mixed with residential functions. A modified form of space syntax analysis is used to analyse and critique the mix of circulation patterns and functions in 15 complex mixed-use buildings. The plans and relational diagrams reveal how different functions are mixed or separated, and the relative spatial depth they penetrate from the street. Five primary circulation diagrams emerge with different degrees of informality in different districts of the city. Under conditions of informal adaptation, vertical functional mix produces benefits in the form of synergies but also problems of privacy and security. To engage effectively planners need a complex understanding of the interrelated spatial, social and economic logics involved.
Ethnobotanical study of medicinal plants utilized in the management of candidiasis in Northern Uganda
Authors: Akwongo Betty , Katuura Esther , Nsubuga Anthony M. , Tugume Patience , Andama Morgan , Anywar Godwin , Namaganda Mary , Asimwe Savina , Kakudidi Esezah Kyomugisha 
Published: October 2022

Abstract
Background
The emergence of resistant Candida species to antifungal drugs has led to resurgence in herbal usage globally. However, little is known about anti-candida plants. This study explored ethnomedicinal plants as treatment option for candidiasis in Pader, Northern Uganda.

Methods
A cross-sectional survey of potential anti-candida plants was conducted using questionnaires, focus group discussions and field observations in March 2022. Sixty-three respondents were selected by snowball technique. The frequencies of respondents/responses were analyzed, associations of respondents’ socio-demographics with indigenous knowledge of herbal usage established by Chi-square (χ2) test using SPSS 27. Informant Consensus Factor was computed to establish level of agreement on herbal usage, and thematic analysis done for focus group discussions.

Results
Candidiasis is still common and troublesome in Pader. All herbalist had equal chances of receiving and treating candidiasis patients irrespective of herbalist’s gender, age, education level, occupation, marital status and religion (p > 0.05). About 39.7% of herbalists received candidiasis patients weekly (p < 0.01). All herbalists had knowledge on candidiasis. Death (56.8%) and discomfort (36.8%) were the major health risks of oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC), respectively. A total of 32 potential anti-candida plant species in 18 families were identified. Families of Fabaceae (9 species) and Asteraceae (5 species) had most plant species. Trees (50.0%) and herbs (43.8%) were the dominant life forms. The commonest plants by frequency of mention were: Momordica foetida (26), Sansevieria dawei (20), Khaya anthotheca (15), Piliostigma thonningii (10), Clerodendrum umbellatum (7), Hallea rubrostipulata (5) and unidentified plant, ‘Agaba/daa layata’ in Acholi dialect (5). Plant parts mainly used were roots (56.3%) and stem barks (15.6%) harvested majorly by cutting (46.9%) and uprooting (12.5%). Most respondents (females, 95%) preferred herbal to western medication (p < 0.01) due to its perceived effectiveness. There was high consensus among herbalists on herbal remedies for OPC and VVC (FIC = 0.9).

Conclusions
Pader communities have diverse indigenous knowledge on candidiasis and prefer herbal medicines to orthodox treatment for candidiasis. However, the herbalists use unsustainable harvesting techniques like uprooting whole plants and cutting main roots. Hence, the need to document such indigenous knowledge before being lost for community usage and scientific validation.
FORT-1: Phase II/III Study of Rogaratinib Versus Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Carcinoma Selected Based on FGFR1/3 mRNA Expression
Authors: Sternberg Cora N. , Petrylak Daniel P. , Bellmunt Joaquim , Nishiyama Hiroyuki , Necchi Andrea , Gurney Howard , Lee Jae-Lyun , van der Heijden Michiel S. , Rosenbaum Eli , Penel Nicolas , Pang See-Tong , Li Jian-Ri , García del Muro Xavier , Joly Florence , Pápai Zsuzsanna , Bao Weichao , Ellinghaus Peter , Lu Chengxing , Sierecki Mitchell , Coppieters Sabine , Nakajima Keiko , Ishida Tatiane Cristine , Quinn David I. 
Published: October 2022

PURPOSE Rogaratinib, an oral pan-fibroblast growth factor receptor (FGFR1-4) inhibitor, showed promising phase I efficacy and safety in patients with advanced urothelial carcinoma (UC) with FGFR1-3 mRNA overexpression. We assessed rogaratinib efficacy and safety versus chemotherapy in patients with FGFR mRNA-positive advanced/metastatic UC previously treated with platinum chemotherapy. METHODS FORT-1 (ClinicalTrials.gov identifier: NCT03410693 ) was a phase II/III, randomized, open-label trial. Patients with FGFR1/ 3 mRNA-positive locally advanced or metastatic UC with ≥ 1 prior platinum-containing regimen were randomly assigned (1:1) to rogaratinib (800 mg orally twice daily, 3-week cycles; n = 87) or chemotherapy (docetaxel 75 mg/m2, paclitaxel 175 mg/m2, or vinflunine 320 mg/m2 intravenously once every 3 weeks; n = 88). The primary end point was overall survival, with objective response rate (ORR) analysis planned following phase II accrual. Because of comparable efficacy between treatments, enrollment was stopped before progression to phase III; a full interim analysis of phase II was completed. RESULTS ORRs were 20.7% (rogaratinib, 18/87; 95% CI, 12.7 to 30.7) and 19.3% (chemotherapy, 17/88; 95% CI, 11.7 to 29.1). Median overall survival was 8.3 months (95% CI, 6.5 to not estimable) and 9.8 months (95% CI, 6.8 to not estimable; hazard ratio, 1.11; 95% CI, 0.71 to 1.72; P = .67). Grade 3/4 events occurred in 37 (43.0%)/4 (4.7%) patients and 32 (39.0%)/15 (18.3%), respectively. No rogaratinib-related deaths occurred. Exploratory analysis of patients with FGFR3 DNA alterations showed ORRs of 52.4% (11/21; 95% CI, 29.8 to 74.3) for rogaratinib and 26.7% (4/15; 95% CI, 7.8 to 55.1) for chemotherapy. CONCLUSION To our knowledge, these are the first data to compare FGFR-directed therapy with chemotherapy in patients with FGFR-altered UC, showing comparable efficacy and manageable safety. Exploratory testing suggested FGFR3 DNA alterations in association with FGFR1/ 3 mRNA overexpression may be better predictors of rogaratinib response.
Genomic Microsatellite Signatures Identify Germline Mismatch Repair Deficiency and Risk of Cancer Onset
Authors: Chung Jiil , Negm Logine , Bianchi Vanessa , Stengs Lucie , Das Anirban , Liu Zhihui Amy , Sudhaman Sumedha , Aronson Melyssa , Brunga Ledia , Edwards Melissa , Forster Victoria , Komosa Martin , Davidson Scott , Lees Jodi , Tomboc Patrick , Samuel David , Farah Roula , Bendel Anne , Knipstein Jeffrey , Schneider Kami Wolfe , Reschke Agnes , Zelcer Shayna , Zorzi Alexandra , McWilliams Robert , Foulkes William D. , Bedgood Raymond , Peterson Lindsay , Rhode Sara , Van Damme An , Scheers Isabelle , Gardner Sharon , Robbins Gabriel , Vanan Magimairajan Issai , Meyn M. Stephen , Auer Rebecca , Leach Brandie , Burke Carol , Villani Anita , Malkin David , Bouffet Eric , Huang Annie , Taylor Michael D. , Durno Carol , Shlien Adam , Hawkins Cynthia , Getz Gad , Maruvka Yosef E. , Tabori Uri ,   on behalf of the International Replication Repair Deficiency Consortium
Published: October 2022

PURPOSE
Diagnosis of Mismatch Repair Deficiency (MMRD) is crucial for tumor management and early detection in patients with the cancer predisposition syndrome constitutional mismatch repair deficiency (CMMRD). Current diagnostic tools are cumbersome and inconsistent both in childhood cancers and in determining germline MMRD.

PATIENTS AND METHODS
We developed and analyzed a functional Low-pass Genomic Instability Characterization (LOGIC) assay to detect MMRD. The diagnostic performance of LOGIC was compared with that of current established assays including tumor mutational burden, immunohistochemistry, and the microsatellite instability panel. LOGIC was then applied to various normal tissues of patients with CMMRD with comprehensive clinical data including age of cancer presentation.

RESULTS

Overall, LOGIC was 100% sensitive and specific in detecting MMRD in childhood cancers (N = 376). It was more sensitive than the microsatellite instability panel (14%,
P
= 4.3 × 10
−12
), immunohistochemistry (86%,
P
= 4.6 × 10
−3
), or tumor mutational burden (80%,
P
= 9.1 × 10
−4
). LOGIC was able to distinguish CMMRD from other cancer predisposition syndromes using blood and saliva DNA (
P
< .0001, n = 277). In normal cells, MMRDness scores differed between tissues (GI > blood > brain), increased over time in the same individual, and revealed genotype-phenotype associations within the mismatch repair genes. Importantly, increased MMRDness score was associated with younger age of first cancer presentation in individuals with CMMRD (
P
= 2.2 × 10
−5
).

CONCLUSION
LOGIC was a robust tool for the diagnosis of MMRD in multiple cancer types and in normal tissues. LOGIC may inform therapeutic cancer decisions, provide rapid diagnosis of germline MMRD, and support tailored surveillance for individuals with CMMRD.
Risk Stratification of Stage I Grade 3 Endometrioid Endometrial Carcinoma in the Era of Molecular Classification
Authors: Zammarrelli William A. , Kim Sarah H. , Da Cruz Paula Arnaud , Rios-Doria Eric V. , Ehmann Sarah , Yeoshoua Effi , Hanlon Etta J. , Zhou Qin , Iasonos Alexia , Alektiar Kaled M. , Aghajanian Carol , Makker Vicky , Leitao Mario M. , Abu-Rustum Nadeem R. , Ellenson Lora H. , Weigelt Britta , Mueller Jennifer J. 
Published: October 2022

PURPOSE The role of adjuvant therapy in stage I grade 3 endometrioid endometrial carcinoma (EEC) is debatable. We sought to define the agreement between Post Operative Radiation Therapy in Endometrial Carcinoma 1 (PORTEC-1) high-intermediate risk (HIR) and Gynecologic Oncology Group (GOG)-99 HIR criteria, assess their concordance with The Cancer Genome Atlas molecular subtypes, and evaluate oncologic outcomes in this population. METHODS We identified patients with stage I grade 3 EECs who underwent surgical staging at our institution from January 2014 to January 2020. Patients were stratified into PORTEC-1 HIR, GOG-99 HIR, and The Cancer Genome Atlas molecular subtypes. Adjuvant treatment, and progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS Seventy-five patients were included. The agreement between PORTEC-1 and GOG-99 HIR classification was 68% (95% CI, 56.2 to 78.3), with a kappa of 0.36 ( P = .001). There was no agreement between PORTEC-1 or GOG-99 HIR classification and a dichotomized molecular classification (copy number-high [CN-H] v other subtypes), with a kappa of 0.03 ( P = .39) and −0.03 ( P = .601), respectively. There was no difference in PFS between PORTEC-1 HIR and non-HIR (HR, 10.9; 95% CI, 0.28 to 4.21) or between GOG-99 HIR and non-HIR (HR, 1.22; 95% CI, 0.32 to 4.6) stage I grade 3 EECs. Patients with CN-H compared with non-CN-H EEC had worse PFS (HR, 5.67; 95% CI, 1.73 to 18.63) and OS (HR, 5.05; 95% CI, 1.13 to 22.5). CONCLUSION In surgically staged patients with stage I grade 3 EEC, PORTEC-1 and GOG-99 HIR criteria were not prognostic and did not identify CN-H patients. Patients with CN-H EEC had worse PFS and OS compared with those with other molecular subtypes. The integration of the molecular classification with recognized clinicopathologic factors may identify patients with higher-risk stage I grade 3 EEC who benefit from additional therapy.
Ketone Body Infusion Abrogates Growth Hormone–Induced Lipolysis and Insulin Resistance
Authors: Høgild Morten Lyng , Hjelholt Astrid Johannesson , Hansen Jakob , Pedersen Steen Bønløkke , Møller Niels , Wojtaszewski Jørgen F P , Johannsen Mogens , Jessen Niels , Jørgensen Jens Otto Lunde 
Published: October 2022

AbstractContextExogenous ketone body administration lowers circulating glucose levels but the underlying mechanisms are uncertain.ObjectiveWe tested the hypothesis that administration of the ketone body β-hydroxybutyrate (βOHB) acutely increases insulin sensitivity via feedback suppression of circulating free fatty acid (FFA) levels.MethodsIn a randomized, single-blinded crossover design, 8 healthy men were studied twice with a growth hormone (GH) infusion to induce lipolysis in combination with infusion of either βOHB or saline. Each study day comprised a basal period and a hyperinsulinemic-euglycemic clamp combined with a glucose tracer and adipose tissue and skeletal muscle biopsies.ResultsβOHB administration profoundly suppressed FFA levels concomitantly with a significant increase in glucose disposal and energy expenditure. This was accompanied by a many-fold increase in skeletal muscle content of both βOHB and its derivative acetoacetate.ConclusionOur data unravel an insulin-sensitizing effect of βOHB, which we suggest is mediated by concomitant suppression of lipolysis.
CXCL12 defines lung endothelial heterogeneity and promotes distal vascular growth
Authors: Chandrasekaran Prashant , Negretti Nicholas M. , Sivakumar Aravind , Liberti Derek C. , Wen Hongbo , Peers de Nieuwburgh Maureen , Wang Joanna Y. , Michki Nigel S. , Chaudhry Fatima N. , Kaur Sukhmani , Lu MinQi , Jin Annabelle , Zepp Jarod A. , Young Lisa R. , Sucre Jennifer M. S. , Frank David B. 
Published: October 2022

ABSTRACT
There is a growing amount of data uncovering the cellular diversity of the pulmonary circulation and mechanisms governing vascular repair after injury. However, the molecular and cellular mechanisms contributing to the morphogenesis and growth of the pulmonary vasculature during embryonic development are less clear. Importantly, deficits in vascular development lead to significant pediatric lung diseases, indicating a need to uncover fetal programs promoting vascular growth. To address this, we used a transgenic mouse reporter for expression of Cxcl12, an arterial endothelial hallmark gene, and performed single-cell RNA sequencing on isolated Cxcl12-DsRed+ endothelium to assess cellular heterogeneity within pulmonary endothelium. Combining cell annotation with gene ontology and histological analysis allowed us to segregate the developing artery endothelium into functionally and spatially distinct subpopulations. Expression of Cxcl12 is highest in the distal arterial endothelial subpopulation, a compartment enriched in genes for vascular development. Accordingly, disruption of CXCL12 signaling led to, not only abnormal branching, but also distal vascular hypoplasia. These data provide evidence for arterial endothelial functional heterogeneity and reveal conserved signaling mechanisms essential for pulmonary vascular development.
Abnormalities in the migration of neural precursor cells in familial bipolar disorder
Authors: Sukumaran Salil K. , Paul Pradip , Guttal Vishwesha , Holla Bharath , Vemula Alekhya , Bhatt Harsimar , Bisht Piyush , Mathew Kezia , Nadella Ravi K. , Varghese Anu Mary , Kalyan Vijayalakshmi , Purushottam Meera , Jain Sanjeev , Consortium ADBS , Sud Reeteka , Viswanath Biju 
Published: October 2022

ABSTRACT
Cellular migration is a ubiquitous feature that brings brain cells into appropriate spatial relationships over time; and it helps in the formation of a functional brain. We studied the migration patterns of induced pluripotent stem cell-derived neural precursor cells (NPCs) from individuals with familial bipolar disorder (BD) in comparison with healthy controls. The BD patients also had morphological brain abnormalities evident on magnetic resonance imaging. Time-lapse analysis of migrating cells was performed, through which we were able to identify several parameters that were abnormal in cellular migration, including the speed and directionality of NPCs. We also performed transcriptomic analysis to probe the mechanisms behind the aberrant cellular phenotype identified. Our analysis showed the downregulation of a network of genes, centering on EGF/ERBB proteins. The present findings indicate that collective, systemic dysregulation may produce the aberrant cellular phenotype, which could contribute to the functional and structural changes in the brain reported for bipolar disorder.
This article has an associated First Person interview with the first author of the paper.