bluuebunny/crossref_metadata_2025_split huggingface dataset:
2-D-gal Targets Terminal Fucosylation to Inhibit T-cell Response in a Mouse Skin Transplant Model
Authors: Mao Kaifeng , Luo Jialiang , Ye Junli , Li Lei , Lin Fenwang , Zhou Minjie , Wang Di , Yu Lu , Zhu Zhengyumeng , Zuo Daming , Ye Junsheng 
Published: November 2022

Background.
Organ allograft rejection is mainly driven by T-cell response. Studies have shown that fucosylation plays essential roles in the immune cell development and function. Terminal fucosylation inhibitor, 2-deoxy-D-galactose (2-D-gal), has been reported to suppress immunoresponse of macrophages, but its effects on T-cell–mediated immune response and transplant rejection have not been fully explored.

Methods.
The terminal fucosylation level in T cells was detected through ulex europaeus agglutinin-I staining. The consequences of 2-D-gal on murine T-cell proliferation, activation, cytokine secretion, and cell cycle were investigated in vitro. T-cell receptor signaling cascades were examined. Last, mouse skin transplant model was utilized to evaluate the regulatory effects of 2-D-gal on T-cell response in vivo.

Results.
The expression of fucosyltransferase1 was upregulated in CD3/CD28-activated T cells along with an elevation of α(1,2)-fucosylation level as seen by ulex europaeus agglutinin-I staining. Furthermore, 2-D-gal suppressed T-cell activation and proliferation, decrease cytokines production, arrest cell cycle, and prevent the activation of T-cell receptor signaling cascades. In vivo experiments showed that 2-D-gal limited T-cell proliferation to prolong skin allograft in mice. This was accompanied by lower level of inflammatory cytokines, and were comparable to those treated with Cyclosporin A.

Conclusions.
Terminal fucosylation appears to play a role in T-cell activation and proliferation, and its inhibitor, 2-D-gal, can suppress T-cell activation and proliferation both in vitro and in vivo. In a therapeutic context, inhibiting terminal fucosylation may be a potential strategy to prevent allogeneic transplant rejection.
Targeting IDH1/IDH2 mutations in gliomas
Authors: de la Fuente Macarena I. 
Published: November 2022

Purpose of review
Somatic point mutations in the metabolic enzyme isocitrate dehydrogenase (IDH) are a defining feature of the majority of WHO grade 2–3 diffuse glioma and the most powerful positive prognostic factor for survival in gliomas. The purpose is to review experimental therapeutic approaches targeting IDH mutations in gliomas including small-molecule inhibitors, immunotherapies, and agents targeting mutant IDH-induced epigenetic and metabolic vulnerabilities.

Recent findings
Extensive preclinical work supports targeting mutant IDH (mIDH) in glioma. In heavily pretreated patients with mIDH glioma, enzyme inhibitors demonstrated to be well tolerated with preliminary evidence of clinical activity in nonenhancing tumors and enhancing tumors when used as single agents. In patients with newly diagnosed WHO grade 3 or 4 astrocytomas, a phase 1 study of a vaccine-targeting IDH1 R132H showed to be well tolerated and demonstrated immunogenicity with a 3-year progression-free and overall survival rates of 0.63 and 0.84, respectively. A variety of ongoing trials aim to target mIDH, including treatments with single agents or combinatory approaches in the upfront or recurrent setting.

Summary
mIDH are commonly found in gliomas and play a key role in gliomagenesis. This has led to studies using agents to directly inhibit them, immunotherapies, and epigenetic/metabolic drugs with varying and promising results. Ongoing studies may elucidate the precise role of these therapies and the best timing for treatment within the disease course.
Immunotherapy approaches for adult glioma: knowledge gained from recent clinical trials
Authors: Andersen Brian M. , Reardon David A. 
Published: November 2022

Purpose of review
Summarize principles behind various immunotherapy approaches for high and low-grade glioma in the context of recently completed clinical trials and the new insights they provide.

Recent findings
Despite the widespread success of therapies targeting the T-cell checkpoints programmed-death 1 and cytotoxic T lymphocyte antigen 4 in other malignancies, recent phase III trials in glioblastoma confirm the lack of efficacy of anti-programmed-death 1 monotherapy in more than 90% of patients. Vaccination approaches remain under investigation for high-grade glioma and have shown activity in some low-grade glioma patients. Chimeric antigen receptor T cells now feature a new generation of products engineered to potentially withstand glucocorticoid therapy. Oncolytic viral therapies have similarly advanced in sophistication, with drug-sensitive gene expression and tumor-selective modifications. Combinations of therapies hold promise for overcoming the numerous mechanisms of immune suppression in glioma.

Summary
Although immunotherapies have yet to show rates of efficacy compared with other malignancies, new knowledge of immunology and combination therapies brings hope for improved efficacy in the future.
Urogenital dysfunction following neurotrauma
Authors: Saraf Udit , Kumar A Anand , Panicker Jalesh N. 
Published: November 2022

Purpose of review
Trauma affecting the nervous system can have widespread consequences, depending on the location and severity of injury. The sensorimotor and cognitive deficits due to neurotrauma have been studied extensively. Although the overall mortality due to neurotrauma has reduced, the disability and morbidity due to neurotrauma has not significantly reduced and focus on urogenital disturbances in these patients has been limited. This article reviews the limited evidence and scientific literature on this topic.

Recent findings
Lower urinary tract symptoms are commonly reported in patients with neurotrauma, both acutely and over the long term. Multiple medical and surgical approaches are available for managing bladder dysfunction in these patients. Sexual dysfunction and changes in sexual behaviour are reported by patients with neurotrauma and are usually multifactorial. Treatment options for sexual dysfunction are available and their management requires a holistic approach.

Summary
Urogenital dysfunction contributes significantly to the overall functional outcome and impaired quality of life in patients with neurotrauma. A better understanding of the mechanisms behind the urogenital abnormalities is needed for efficient management and treatment.
The Efficacy and Safety of Adjuvant Lomustine to Chemotherapy for Recurrent Glioblastoma: A Meta-analysis of Randomized Controlled Studies
Authors: Fu Xiaojuan , Shi Dijian , Feng Yimo 
Published: November 2022

Introduction
Lomustine is regarded as 1 common anti–vascular endothelial growth factor agent. The efficacy of adjuvant lomustine to chemotherapy remains controversial for recurrent glioblastoma. We conduct this meta-analysis to explore the influence of adjuvant lomustine on treatment efficacy of recurrent glioblastoma.

Methods
We have searched PubMed, EMBASE, Web of Science, EBSCO, and Cochrane library databases through August 2019 and included randomized controlled trials assessing the efficacy and safety of adjuvant lomustine for recurrent glioblastoma.

Results
Four randomized controlled trials are included in the meta-analysis. Overall, compared with the control group for recurrent glioblastoma, adjuvant lomustine has no substantial effect on objective response (risk ratio [RR], 1.32; 95% confidence interval [CI], 0.91 to 1.93; P = 0.15), complete response (RR, 1.76; 95% CI, 0.26–11.90; P = 0.56), progressive response (RR, 1.32; 95% CI, 0.88–1.99; P = 0.18), median progression-free survival (standard mean difference [SMD], 0.73; 95% CI, −0.65 to 2.11; P = 0.30), or median overall survival (SMD, 0.26; 95% CI, −0.30–0.83; P = 0.36), but results in the increase in 6-month progression-free survival (SMD, 1.71; 95% CI, 0.38–3.04; P = 0.01). There is no increase in grade ≥3 adverse events after adjuvant lomustine treatment (RR, 1.55; 95% CI, 0.84–2.89; P = 0.16) compared with control intervention.

Conclusions
Adjuvant lomustine to other chemotherapy may provide no obvious benefits for the treatment of recurrent glioblastoma.
Critical Appraisal of the Quality of Publications in Hepatobiliary and Pancreatic Surgery Research Using the American College of Surgeons NSQIP Database
Authors: Hockett Diana , Rabinowitz Judy B , Kwon Yong K , Joseph Bellal , Kaafarani Haytham , Aziz Hassan 
Published: November 2022

Background:
The use of the American College of Surgeons (ACS) NSQIP has increased in hepatobiliary and pancreatic surgery (HPB) research as it provides access to high-quality surgical outcome data on a national scale. Using the ACS-NSQIP database, this study examined the methodological reporting of HPB publications.

Study Design:
Web of Science core collection (all editions) was queried for all HPB studies using the ACS-NSQIP database published between 2004 and 2022. In addition, a critical appraisal was performed using the JAMA (Journal of American Medical Association)-Surgery Checklist, STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) Statement, and RECORD (Reporting of studies Conducted using Observational Routinely-collected Health Data) Statement.

Results:
In total, 276 studies were included in the analysis. The median scores for the JAMA-Surgery Checklist, RECORD Statement, and STROBE Statement were 4 of 7 (IQR 3, 5), 3 of 10 (IQR 2, 4), and 15 of 21 (IQR 13, 17), respectively. The criteria with the highest rates of nonadherence were discussing competing risks, clear definitions of inclusion and exclusion criteria, unadjusted and adjusted outcomes, provision of supplementary data, and performing subgroup analyses. Additionally, when examining checklist fulfillment of hepatobiliary studies and pancreatic studies separately, pancreatic studies demonstrated significantly greater fulfillment of the STROBE Statement checklist items.

Conclusion:
Satisfactory reporting of methodology is present among HPB studies utilizing the ACS-NSQIP database, with multiple opportunities for improvement. Areas for improved adherence include discussing competing risks, providing supplementary information, and performing appropriate subgroup analysis. Given the increasing role of large-scale databases in surgical research, enhanced commitment to reporting guidelines may advance HPB research and ensure quality reporting.
A Tale of Two Waves: Diverse Genomic and Transmission Landscapes Over 15 Months of the COVID-19 Pandemic in Pune, India
Authors: Niveditha Divya , Khan Soumen , Khilari Ajinkya , Nadkarni Sanica , Bhalerao Unnati , Kadam Pradnya , Yadav Ritu , Kanekar Jugal B , Shah Nikita , Likhitkar Bhagyashree , Sawant Rutuja , Thakur Shikha , Tupekar Manisha , Nagar Dhriti , Rao Anjani G. , Jagtap Rutuja , Jogi Shraddha , Belekar Madhuri , Pathak Maitryee , Shah Priyanki , Ranade Shatakshi , Phadke Nikhil , Das Rashmita , Joshi Suvarna , Karyakarte Rajesh , Ghose Aurnab , Kadoo Narendra , Shashidhara LS , Monteiro Joy Merwin , Shanmugam Dhanasekaran , Raghunathan Anu , Karmodiya Krishanpal 
Published: November 2022

SummaryThe modern response to pandemics, critical for effective public health measures, is shaped by the availability and integration of diverse epidemiological outbreak data. Genomic surveillance has come to the forefront during the coronavirus disease 2019 (COVID-19) pandemic at both local and global scales to identify variants of concern. Tracking variants of concern (VOC) is integral to understanding the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in space and time. Combining phylogenetics with epidemiological data like case incidence, spatial spread, and transmission dynamics generates actionable information. Here we discuss the genome surveillance done in Pune, India, through sequencing 10,496 samples from infected individuals and integrating them with multiple heterogeneous outbreak data. The rise and fall of VOCs along with shifting transmission dynamics in the time interval of December 2020 to March 2022 was identified. Population-based estimates of the proportion of circulating variants indicated the second and third peak of infection in Pune to be driven by VOCs Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) respectively. Integrating single nucleotide polymorphism changes across all sequenced genomes identified C (Cytosine) > T (Thymine) and G (Guanine) > T (Thymine) substitutions to dominate with higher rates of adaptive evolution in Spike (S), RNA-dependent RNA polymerase (RdRp), and Nucleocapsid (N) genes. Spike Protein mutational profiling during and pre-Omicron VOCs indicated differential rank ordering of high-frequency mutations in specific domains that increased the charge and binding properties of the protein. Time-resolved phylogenetic analysis of Omicron sub-lineages identified specific recombinant X lineages, XZ, XQ, and XM. BA.1 from Pune was found to be highly divergent by global sequence alignment and hierarchical clustering. Our “band of five” outbreak data analytics that includes the integration of five heterogeneous data types indicates that a strong surveillance system with comprehensive high-quality metadata was critical to understand the spatiotemporal evolution of the SARS-CoV-2 genome in Pune. We anticipate the use of such integrated workflows to be critical for pandemic preparedness in the future.
Exome Array Analysis of 9,721 ischemic stroke cases from the SiGN Consortium
Authors: Xu Huichun , Nguyen Kevin , Gaynor Brady , Ling Hua , Zhao Wei , McArdle Patrick F. , O’Connor Timothy , Stine O Colin , Ryan Kathleen A. , Lynch Megan , Smith Jennifer A. , Faul Jessica D. , Hu Yao , Haessler Jeffrey W. , Fornage Myriam , Kooperberg Charles ,   the Trans-Omics for Precision Medicine (TOPMed) Stroke Working Group, Perry James A. , Hong Charles C. , Cole John W. , Pugh Elizabeth , Doheny Kimberly , Kardia Sharon L.R. , Weir David R. , Kittner Steven J. , Mitchell Braxton D. ,   the SiGN Consortium
Published: November 2022

AbstractRecent studies have identified > 40 genetic variants robustly associated with ischemic stroke, most identified through genome wide association studies and primarily marking common variants in non-coding regions presumed to have regulatory roles on gene and protein expression. To evaluate the contribution of coding variants, which are mostly rare, to the etiology of ischemic stroke, we performed an exome array analysis of 9,721 ischemic stroke cases with mean age of onset at 67.1 years from the SiGN Consortium, and 12,345 subjects with no history of stroke (mean age 67.0 years) from the Health Retirement Study and SiGN consortium. Both cohorts included people with diverse ancestries. Genotyping for both SiGN and HRS was performed using similar array content at the Center for Inherited Disease Research (CIDR), albeit as two separate studies. Following extensive SNP- and sample-level quality control, a total of 106,101 SNPs from the exome content was used for exome association analysis. We identified 15 coding variants significantly associated with all ischemic stroke at array-wide threshold for statistical significance (i.e., p < 3.6 × 10−7) that also showed good genotyping quality, including two common SNPs inABOthat have previously been associated with stroke. Twelve of the remaining 13 variants were extremely rare in European Caucasians (MAF<0.1%) and the associations were driven by substantially higher allele frequencies in African American cases than in African American controls. A variant inPRIM2, rs199585353, was present exclusively in the stroke cases of European Caucasians while absent in all other samples from our data. There was no evidence for replication of these associations in either TOPMed Stroke samples (n = 5613 cases) or UK Biobank (n = 5,874 stroke cases), although power to replicate was very low given the low allele frequencies of the associated variants. In conclusion our analyses revealed 13 novel associations, but the low allele counts of associated variants and difficulty in acquiring large, well-powered replication highlight the challenges of rare variant association analysis, especially using array-based genotyping technologies.
Cortico-ocular coupling in the service of episodic memory formation
Authors: Popov Tzvetan , Staudigl Tobias 
Published: November 2022

AbstractEncoding of visual information is a necessary requirement for most types of episodic memories. In search for a neural signature of memory formation, amplitude modulation of neural activity has been repeatedly shown to correlate with and suggested to be functionally involved in successful memory encoding. We here report a complementary view on why and how brain activity relates to memory, indicating a functional role of cortico-ocular interactions for episodic memory formation. Recording simultaneous magnetoencephalography and eye tracking in 35 human participants, we demonstrate that gaze variability and amplitude modulations of alpha/beta oscillations (10-20 Hz) in visual cortex covary and predict subsequent memory performance between and within participants. Amplitude variation during pre-stimulus baseline was associated with gaze direction variability, echoing the co-variation observed during scene encoding. We conclude that encoding of visual information engages unison coupling between oculomotor and visual areas in the service of memory formation.
Views and experiences of Every Mind Matters, Public Health England’s adult mental health literacy campaign: a qualitative interview study
Authors: Stuart Ruth , Shah Prisha , Olive Rachel Rowan , Trevillion Kylee , Henderson Claire 
Published: November 2022

AbstractBackgroundEvery Mind Matters is a publicly funded health campaign, launched in England in 2019, to equip adults to look after their mental health, and that of others, by offering online information about common problems: anxiety, low mood, sleep, stress. This study is one component of an independent evaluation of Every Mind Matters conducted by the NIHR Mental Health Policy Research Unit. Its aim is to explore individuals’ experiences and views of the Every Mind Matters campaign and website.MethodsFour researchers, including three with lived experience of using mental health services, conducted 20, one-off, semi-structured, online interviews with a range of adult participants, including a sample of EMM users and a purposively recruited sub-sample known to have severe or long-term mental health conditions. The team took a codebook approach to the analysis of the transcripts and identified four main themes.FindingsThere was an expectation from the name Every Mind Matters that its advice would address everyone. Almost all participants had experience of mental distress and looked to Every Mind Matters for help with a current problem for themselves.All participants were complimentary about the Every Mind Matters website and found it to be user-friendly (theme 1) and personalised (theme 2) especially the interactive feature ‘Your Mind Plan quiz’ which responds with suggested actions to improve wellbeing and follows up with reminder emails. A few participants found this life changing.Some participants wanted Every Mind Matters to better acknowledge the contexts in which they live (theme 3) such as the limitations of health conditions and health services, and difficulties of crowded housing, social policy, and climate change. Many participants would like Every Mind Matters to do more (theme 4), offer more interactivity, more choice, more information about available treatments, and more stratified advice to cover more severe mental health conditions so that everyone is included.ConclusionThe population that experiences common mental health difficulties is not separate from the population that has severe mental health problems. Every Mind Matters could continue and build on its success by addressing a wider range of needs.
Preliminary Validation of a Structural Magnetic Resonance Imaging Metric for Tracking Dementia-Related Neurodegeneration and Future Decline
Authors: Kress Gavin T , Popa Emily S. , Thompson Paul M , Bookheimer Susan Y , Thomopoulos Sophia I , Ching Christopher RK , Zheng Hong , Merrill David A. , Panos Stella E , Siddarth Prabha , Bramen Jennifer E 
Published: November 2022

AbstractCurrent Alzheimer’s disease (AD) research has a major focus on validating and discovering noninvasive biomarkers that can detect AD, benchmark disease severity, and aid in testing the efficacy of interventions. Structural magnetic resonance imaging (sMRI) is a well-validated tool used in diagnosis and for monitoring disease progression in AD. Much of the sMRI literature centers around hippocampal and other medial temporal lobe structure atrophy, which are strongly associated with cognition and diagnosis. Because atrophy patterns are complex and vary by patient, researchers have made efforts to condense more brain information into validated metrics. Many of these methods use machine learning (ML), which can be difficult to interpret clinically, hampering clinical adoption. Here, we introduce a practical, clinically meaningful and interpretable index which we call an “AD-NeuroScore.” Our approach is automated and uses multiple regional brain volumes associated with cognitive decline. We used a modified Euclidean inspired distance function to calculate the differences between each participant and a cognitively normal (CN) older adult template, adjusting for intracranial volume, age, sex, and scanner model. Here we report validation results, including sensitivity to diagnosis (CN, mild cognitive impairment (MCI), and AD) and disease severity (Clinical Dementia Rating Scale Sum of Boxes (CDR-SB), Mini Mental State Exam (MMSE), and Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-11) in 929 older adults (mean age=72.7 years, SD=6.3, Range=55.1-91.5, 50% Female) drawn from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. To determine if AD-NeuroScore might be predictive of disease progression, we assessed the relationship between the calculated AD-NeuroScore at baseline and change in both diagnosis and disease severity scores at 12, 24, 36, and 48-months. We performed additional validation in all analyses, benchmarking AD-NeuroScore against adjusted hippocampal volume (AHV). We found that AD-NeuroScore was significantly associated with diagnosis and all disease severity scores at baseline. Associations between AD-NeuroScore and disease severity (CDR-SB and ADAS-11) were significantly stronger than with AHV. Baseline AD-NeuroScore was also associated with change in diagnosis and changes in disease severity scores at all time points. Performance was equivalent, or in some cases superior, to AHV. These early validation results suggest that AD-NeuroScore has the potential to be a clinically meaningful biomarker for dementia.