bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant Transcript Usage Is Associated with Homologous Recombination Deficiency and Predicts Therapeutic Response
Authors: Kang Hyeon Gu , Hwangbo Haeun , Kim Myung Ji , Kim Sinae , Lee Eun Ji , Park Min Ji , Kim Jae-Weon , Kim Byoung-Gie , Cho Eun-Hae , Chang Suhwan , Lee Jung-Yun , Choi Jung Kyoon 
Published: October 2021

Abstract

BRCA1/2 mutations account for only a small fraction of homologous recombination (HR) deficiency (HRD) cases. Recently developed genomic HRD (gHRD) tests suffer confounding factors that cause low precision in predicting samples that will respond to PARP inhibitors and DNA damaging agents. Here we present molecular and clinical evidence of transcriptional HRD (tHRD) that is based on aberrant transcript usage (aTU) of minor isoforms. Specifically, increased TU of nonfunctional isoforms of DNA repair genes was prevalent in breast and ovarian cancer with gHRD. Functional assays validated the association of aTU with impaired HR activity. Machine learning–based tHRD detection by the transcript usage (TU) pattern of key genes was superior to directly screening for gHRD or BRCA1/2 mutations in accurately predicting responses of cell lines and patients with cancer to PARP inhibitors and genotoxic drugs. This approach demonstrated the capability of tHRD status to reflect functional HR status, including in a cohort of olaparib-treated ovarian cancer with acquired platinum resistance. Diagnostic tests based on tHRD are expected to broaden the clinical utility of PARP inhibitors.

Significance:
A novel but widespread transcriptional mechanism by which homologous recombination deficiency arises independently of BRCA1/2 mutations can be utilized as a companion diagnostic for PARP inhibitors.
U.S. FDA Drug Approvals for Gynecological Malignancies: A Decade in Review
Authors: Arora Shaily , Narayan Preeti , Ison Gwynn , Berman Tara , Suzman Daniel L. , Wedam Suparna , Prowell Tatiana M. , Ghosh Soma , Philip Reena , Osgood Christy L. , Gao Jennifer J. , Shah Mirat , Krol Danielle , Wahby Sakar , Royce Melanie , Brus Christina , Bloomquist Erik W. , Fiero Mallorie H. , Tang Shenghui , Pazdur Richard , Ibrahim Amna , Amiri-Kordestani Laleh , Beaver Julia A. 
Published: October 2021

Abstract
Over the last decade, there has been tremendous progress in the treatment of patients with gynecologic cancers with a changing therapy landscape. This summary provides an overview of U.S. Food and Drug Administration (FDA) approvals for gynecologic cancers from 2010 to 2020, totaling 17 new indications. For each of the approved indications, endpoints, trial design, results, and regulatory considerations are outlined. Among these 17 indications, six received accelerated approval (AA) and 11 received regular approval (RA). As of September 2021, of the six AA, three have subsequently demonstrated clinical benefit resulting in conversion to RA and the remaining three have ongoing clinical trials that have not yet reported results. Approval decisions for these 17 indications were supported by primary efficacy endpoints of progression-free survival (n = 10), objective response rate (n = 6), and overall survival (n = 1) and showed a favorable benefit–risk profile. Among the 17 indications, 15 received priority review and three applications participated in one or more novel Oncology Center of Excellence initiatives, including Real Time Oncology Review, Assessment Aid, and Project Orbis. Current FDA thinking on drug development opportunities and regulatory initiatives currently under way will be discussed.
U.S. FDA Drug Approvals for Breast Cancer: A Decade in Review
Authors: Arora Shaily , Narayan Preeti , Osgood Christy L. , Wedam Suparna , Prowell Tatiana M. , Gao Jennifer J. , Shah Mirat , Krol Danielle , Wahby Sakar , Royce Melanie , Ghosh Soma , Philip Reena , Ison Gwynn , Berman Tara , Brus Christina , Bloomquist Erik W. , Fiero Mallorie H. , Tang Shenghui , Pazdur Richard , Ibrahim Amna , Amiri-Kordestani Laleh , Beaver Julia A. 
Published: October 2021

Abstract
Over the last decade, the treatment of patients with breast cancer has been greatly impacted by the approval of multiple drugs and indications. This summary describes 30 FDA approvals of treatments for breast cancer from 2010 to 2020. The trial design endpoints, results, and regulatory considerations are described for each approved indication. Of the 30 indications, 23 (76.6%) received regular and 7 (23.3%) received accelerated approval. Twenty-six approvals were granted in metastatic breast cancer (MBC) and four in early breast cancer. Approval decisions for the 26 MBC indications were initially supported by progression-free survival (PFS) in 21 (80.8%), overall survival (OS) or a combination of OS and PFS in two (7.7%), and objective response rate (ORR) in three (11.5%). The four approvals in early breast cancer utilized pathologic complete response (pCR) in one (25%) and invasive disease-free survival (iDFS) in three (75%) trials. Among the 30 indications, 22 received priority review, seven were granted Breakthrough Therapy Designation, and 10 applications participated in one or more pilot Oncology Center of Excellence regulatory review initiatives, including Real Time Oncology Review, Assessment Aid, and Project Orbis. FDA initiatives to advance breast cancer drug development are also described.
A new species of&nbsp;Galerina&nbsp;(Hymenogastraceae, Agaricales) from northeast China
Authors: LIU XIAOLIANG , BAU TOLGOR 
Published: October 2021

Galerina variibasidia, a new species in the Hymenogastraceae, was discovered in Arxan, Inner Mongolia Autonomous Region, China. This species is presented with morphological description, illustrations, and supported by phylogenetic analyses using Maximum Likelihood and Bayesian Inference analyses with the internal transcribed spacer rDNA sequences.
Diagnosis of primary ciliary dyskinesia: discrepancy according to different algorithms
Authors: Nussbaumer Mirjam , Kieninger Elisabeth , Tschanz Stefan A. , Savas Sibel T. , Casaulta Carmen , Goutaki Myrofora , Blanchon Sylvain , Jung Andreas , Regamey Nicolas , Kuehni Claudia E. , Latzin Philipp , Müller Loretta 
Published: October 2021

BackgroundDiagnosis of primary ciliary dyskinesia (PCD) is challenging since there is no gold standard test. The European Respiratory (ERS) and American Thoracic (ATS) Societies developed evidence-based diagnostic guidelines with considerable differences.ObjectiveWe aimed to compare the algorithms published by the ERS and the ATS with each other and with our own PCD-UNIBE algorithm in a clinical setting. Our algorithm is similar to the ERS algorithm with additional immunofluorescence staining. Agreement (Cohen's κ) and concordance between the three algorithms were assessed in patients with suspicion of PCD referred to our diagnostic centre.ResultsIn 46 out of 54 patients (85%) the final diagnosis was concordant between all three algorithms (30 PCD negative, 16 PCD positive). In eight patients (15%) PCD diagnosis differed between the algorithms. Five patients (9%) were diagnosed as PCD only by the ATS, one (2%) only by the ERS and PCD-UNIBE, one (2%) only by the ATS and PCD-UNIBE, and one (2%) only by the PCD-UNIBE algorithm. Agreement was substantial between the ERS and the ATS (κ=0.72, 95% CI 0.53–0.92) and the ATS and the PCD-UNIBE (κ=0.73, 95% CI 0.53–0.92) and almost perfect between the ERS and the PCD-UNIBE algorithms (κ=0.92, 95% CI 0.80–1.00).ConclusionThe different diagnostic algorithms lead to a contradictory diagnosis in a considerable proportion of patients. Thus, an updated, internationally harmonised and standardised PCD diagnostic algorithm is needed to improve diagnostics for these discordant cases.
Complete genomic sequence and phylogenomics analysis of Agrobacterium strain AB2/73: a new Rhizobium species with a unique mega-Ti plasmid
Authors: Hooykaas Marjolein J. G. , Hooykaas Paul J. J. 
Published: October 2021

Abstract
Background
The Agrobacterium strain AB2/73 has a unique host range for the induction of crown gall tumors, and contains an exceptionally large, over 500 kbp mega Ti plasmid. We used whole genome sequencing to fully characterize and comparatively analyze the complex genome of strain AB2/73, including its Ti plasmid and virulence factors.

Results
We obtained a high-quality, full genomic sequence of AB2/73 by a combination of short-read Illumina sequencing and long-read Nanopore sequencing. The AB2/73 genome has a total size of 7,266,754 bp with 59.5% GC for which 7012 genes (6948 protein coding sequences) are predicted. Phylogenetic and comparative genomics analysis revealed that strain AB2/73 does not belong to the genus Agrobacterium, but to a new species in the genus Rhizobium, which is most related to Rhizobium tropici. In addition to the chromosome, the genome consists of 6 plasmids of which the largest two, of more than 1 Mbp, have chromid-like properties. The mega Ti plasmid is 605 kbp in size and contains two, one of which is incomplete, repABC replication units and thus appears to be a cointegrate consisting of about 175 kbp derived from an unknown Ti plasmid linked to 430 kbp from another large plasmid. In pTiAB2/73 we identified a complete set of virulence genes and two T-DNAs. Besides the previously described T-DNA we found a larger, second T-DNA containing a 6b-like onc gene and the acs gene for agrocinopine synthase. Also we identified two clusters of genes responsible for opine catabolism, including an acc-operon for agrocinopine degradation, and genes putatively involved in ridéopine catabolism. The plasmid also harbours tzs, iaaM and iaaH genes for the biosynthesis of the plant growth regulators cytokinin and auxin.

Conclusions
The comparative genomics analysis of the high quality genome of strain AB2/73 provided insight into the unusual phylogeny and genetic composition of the limited host range Agrobacterium strain AB2/73. The description of its unique genomic composition and of all the virulence determinants in pTiAB2/73 will be an invaluable tool for further studies into the special host range properties of this bacterium.
Molecular mechanism of modulating miR482b level in tomato with botrytis cinerea infection
Authors: Wu Fangli , Xu Jinfeng , Gao Tiantian , Huang Diao , Jin Weibo 
Published: October 2021

Abstract
Background
Plant miRNAs are involved in the response to biotic and abiotic stresses by altering their expression levels, and they play an important role in the regulation of plant resistance to stress. However, the molecular mechanism that regulates the expression levels of miRNAs in plants with biotic and abiotic stress still needs to be explored. Previously, we found that the expression of the miR482 family was changed in tomato infected by Botrytis cinerea. In this study, we investigated and uncovered the mechanism underlying the response of miR482 to B. cinerea infection in tomato.

Results
First, RT-qPCR was employed to detect the expression patterns of miR482b in tomato infected by B. cinerea, and results showed that miR482b primary transcripts (pri-miR482b) were up-regulated in B. cinerea-infected leaves, but the mature miR482b was down-regulated. Subsequently, we used rapid amplification cDNA end method to amplify the full-length of pri-miR482b. Result showed that the pri-miR482b had two isoforms, with the longer one (consisting 300 bp) having an extra fragment of 53 bp in the 3’-end compared with the shorter one. In vitro Dicer assay indicated that the longer isoform pri-miR482b-x1 had higher efficiency in the post-transcriptional splicing of miRNA than the shorter isoform pri-miR482b-x2. In addition, the transcription level of mature miR482b was much higher in transgenic Arabidopsis overexpressing pri-miR482b-x1 than that in OE pri-miR482b-x2 Arabidopsis. These results confirmed that this extra 53 bp in pri-miR482b-x1 might play a key role in the miR482b biogenesis of post-transcription processing.

Conclusions
Extra 53 bp in pri-miR482b-x1 enhanced miR482b biogenesis, which elevated the transcription level of miR482b. This study clarified the response of miR482 to B. cinerea infection in tomato, thereby helping us further understand the molecular mechanisms that regulate the expression levels of other miRNAs.
The burden of COVID-19 infection in a rural Tamil Nadu community
Authors: Isaac R. , Paul B. , Finkel M. , Moorthy M. , Venkateswaran S. , Bachmann T. T. , Pinnock H. , Norrie J. , Ramalingam S. , Minz S. , Hansdak S. , Blythe R. , Keller M. , Muliyil J. , Weller D. 
Published: October 2021

AbstractBackgroundThere have been over 30 million cases of COVID-19 in India and over 430,000 deaths. Transmission rates vary from region to region, and are influenced by many factors including population susceptibility, travel and uptake of preventive measures. To date there have been relatively few studies examining the impact of the pandemic in lower income, rural regions of India. We report on a study examining COVID-19 burden in a rural community in Tamil Nadu.MethodsThe study was undertaken in a population of approximately 130,000 people, served by the Rural Unit of Health and Social Affairs (RUHSA), a community health center of CMC, Vellore. We established and evaluated a COVID-19 PCR-testing programme for symptomatic patients—testing was offered to 350 individuals, and household members of test-positive cases were offered antibody testing. We also undertook two COVID-19 seroprevalence surveys in the same community, amongst 701 randomly-selected individuals.ResultsThere were 182 positive tests in the symptomatic population (52.0%). Factors associated with test-positivity were older age, male gender, higher socioeconomic status (SES, as determined by occupation, education and housing), a history of diabetes, contact with a confirmed/suspected case and attending a gathering (such as a religious ceremony, festival or extended family gathering). Amongst test-positive cases, 3 (1.6%) died and 16 (8.8%) suffered a severe illness. Amongst 129 household contacts 40 (31.0%) tested positive. The two seroprevalence surveys showed positivity rates of 2.2% (July/Aug 2020) and 22.0% (Nov 2020). 40 tested positive (31.0%, 95% CI: 23.02 − 38.98). Our estimated infection-to-case ratio was 31.7.ConclusionsA simple approach using community health workers and a community-based testing clinic can readily identify significant numbers of COVID-19 infections in Indian rural population. There appear, however, to be low rates of death and severe illness, although vulnerable groups may be under-represented in our sample. It’s vital these lower income, rural populations aren’t overlooked in ongoing pandemic monitoring and vaccine roll-out in India.
Clinicopathological characteristics and prognosis of patients with IgA nephropathy and renal vasculitic lesions
Authors: Tang Xueqing , Wen Qiong , Zhou Qian , Chen Wei 
Published: October 2021

Abstract
Background
We studied patients with IgA nephropathy (IgAN) and compared those with and without renal vasculitic lesions (RVLs).

Methods
From January 2006 to December 2011, patients with biopsy-proven primary IgAN at our institution were retrospectively examined and assigned to an RVL group or a no-RVL group. RVLs were defined as thromboses in arteries and/or arterioles, necrosis of capillary loops, crescent formation, and fibrinoid necrosis of small blood vessels. The association of RVLs with clinical outcomes was analyzed using multivariate models. The primary composite endpoint was end-stage renal disease or doubling of serum creatinine.

Results
There were 1570 patients, 50.2% (788) with RVLs and 49.8% (782) without RVLs. The RVL group was younger; had shorter disease course, more severe proteinuria and hematuria, worse renal function; and were prescribed more steroids and/or immunosuppressants. The RVL group had a greater prevalence of global glomerular sclerosis, more crescents, and a higher Oxford classification grade. A total of 501 patients in the RVL group (50.7%) and 487 in the no-RVL group (49.3%) completed follow-up. The RVL group was more likely to reach the composite endpoint after 1, 3, and 5 years (all P < 0.001). Proteinuria, anemia, low eGFR, and global and segmental sclerosis were independent predictors of progression to the composite endpoint in patients with RVLs.

Conclusions
Almost half of our IgAN patients had RVLs, and these patients were younger and had worse renal function, with more severe proteinuria, hematuria, and severe pathologic lesions. IgAN patients with RVLs had worse renal outcomes than those without RVLs.
Differences in the factors associated with tongue pressure between children with class I and Class II malocclusions
Authors: Fujita Yuko , Ohno Yoma , Ohno Keitaro , Takeshima Tomohiro , Maki Kenshi 
Published: October 2021

Abstract
Background
The relationship between tongue pressure and masticatory performance during the mixed dentition period in cases of Class II malocclusion has not been clarified. The aim of this study was to determine differences in tongue pressure-related factors, including maxillofacial morphology and masticatory performance, between Class I and Class II malocclusions during the mixed dentition period.

Methods
A total of 56 children with Class I malocclusion (12 boys, 16 girls) or Class II malocclusion (16 boys, 12 girls) with mixed dentition were included in the present study. Height, body weight, hand grip strength, maximum occlusal force, maximum tongue pressure, masticatory performance, and the number of decayed, missing, and filled teeth were measured in all participants. Their lateral cephalograms were also evaluated. The means of all measurements were compared between Class I and Class II malocclusions. Pearson’s correlation coefficients were used to determine associations between maximum tongue pressure and other variables for each type of malocclusion.

Results
The maximum tongue pressure, hand grip strength, and maximum occlusal force in the Class II malocclusion group were significantly lower than those in the Class I malocclusion group (all, p < 0.05). The maximum tongue pressure was significantly positively correlated with hand grip strength, maximum occlusal force, masticatory performance, and SNB (sella, nasion, B point) angle in the Class I group (all, p < 0.05), and with height, body weight, and labial inclination of the central incisors in the Class II group (all, p < 0.05).

Conclusions
The maxillofacial morphometric factors associated with tongue pressure were clearly different between cases of Class I and Class II malocclusion with mixed dentition. Masticatory performance and tongue pressure were significantly positively correlated in cases of Class I malocclusion, but not in cases of Class II malocclusion.
Process research: compare and contrast the recovery-orientated strengths model of case management and usual community mental health care
Authors: Tse Samson , Ng Catalina S. M. , Yuen Winnie W. Y. , Lo Iris W. K. , Fukui Sadaaki , Goscha Richard J. , Wan Eppie , Wong Stephen , Chan Sau-Kam 
Published: October 2021

Abstract
Background
The strengths model of case management (SMCM), which was developed by Rapp and Goscha through collaborative efforts at the University of Kansas, assists individuals with mental illness in their recovery by mobilizing individual and environmental resources. Increasing evidence has shown that the utilization of the SMCM improves outcomes, including increased employment/educational attainment, reduced hospitalization rates, higher self-efficacy, and hope. However, little is known about the processes through which the SMCM improves outcomes for mental health service users. This study explores the views of case workers and service users on their experience of providing or receiving the SMCM intervention.

Methods
A qualitative design was employed using individual interviews with service users and case workers drawn from two study conditions: the SMCM group and the control group (treatment as usual). For both study conditions, service users were recruited by either centres-in-charge or case workers from integrated community centres for mental wellness (ICCMWs) operated by three non-governmental organizations (NGOs) in different districts of Hong Kong. Through purposeful sampling, 24 service users and 14 case workers from the SMCM and control groups joined the study. We used an inductive approach to analyse the qualitative data.

Results
We identified two overarching themes: service users’ and case workers’ (1) perceptions of the impacts of the interventions (SMCM and control group) and (2) experiences of the interventions, such as features of the interventions and the factors that facilitated the outcomes. The results showed that there were improvements in the functional recovery of the SMCM group in areas such as employment and family relationships, how self-identified goals were achieved, and how service users gained a better understanding of their own strengths and weaknesses. Regarding their experience of the interventions, participants in both the SMCM group and the control group reported that a good relationship between service users and case workers was vital. However, some concerns were raised about the use of SMCM tools, including the strengths assessment and the personal recovery plan (PRP) and the risk of case workers being subjective in the presentation of cases in group supervision sessions.

Conclusion
The results were promising in terms of supporting the use of the SMCM, with some refinements, in mental health services for Chinese clients.

Trial registration
The Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617001435370, registered on 10/10/2017.
Associations of plasma 8-iso-prostaglandin F2αlevels with fasting blood glucose (FBG) and intra-abdominal fat (IAF) area in various Glycometabolism populations
Authors: Ma Ning , Zhang Yujian , Liu Binbin , Jia Xiaojiao , Wang Rui , Lu Qiang 
Published: October 2021

AbstractBackgroundThis study aimed to investigate the differences in oxidative stress (OS) levels represented by 8-iso-prostaglandin F2α(8-iso-PGF2α) and analyze its correlation with the intra-abdominal fat (IAF) area and the glycolipid index.MethodsWe recruited a total of 160 eligible subjects. According to the blood glucose levels and the T2DM duration, subjects were divided into three groups: Type 2 Diabetes (T2DM) group, Prediabetic group, and Normal glucose-tolerance (NC) group, containing 66, 41, 53 patients, respectively. T2DM groups were additionally divided into a new-onset T2DM group including 29 patients and a non-new-onset T2DM group including 37 patients. General clinical data and biochemical indicators were collected. Intra-abdominal fat (IAF) was measured by MRI. 8-iso-PGF2αwas measured by ELISA.ResultsCompared with the NC group, levels of systolic blood pressure (SBP), waist-to-hip ratio (WHR), FBG, 2 h postprandial glycemia(2hPG), 2 h insulin (2 h INS), IAF area, HOMA-IR, and 8-iso-PGF2αincreased, and high-density lipoprotein cholesterol (HDL-C) decreased in T2DM groups and Prediabetic group (P < 0.05). The 2 h INS level was the highest in the Prediabetic group; 2hPG, and IAF area were the highest in the new-onset T2DM group; WHR, FBG, HOMA-IR and 8-iso-PGF2αwere the highest in the non-new-onset T2DM group. Multiple stepwise regression analysis identified IAF area and FBG as the strongest and independent determinant of 8-iso-PGF2α(P < 0.01).ConclusionsIn various glycometabolism populations, 8-iso-PGF2α is significantly correlated with FBG and IAF, this suggests that high blood glucose and abdominal obesity can increase the damage related to the OS in vivo.