bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive survival movement strategy to local epidemic outbreaks in cyclic models
Authors: Menezes J , Moura B , Rangel E
Published: November 2022

We study the generalised rock-paper-scissors game with five species whose organisms face local epidemic outbreaks. As an evolutionary behavioural survival strategy, organisms of one out of the species move in the direction with more enemies of their enemies to benefit from protection against selection. We consider that each organism scans the environment, performing social distancing instead of agglomerating when perceiving that the density of sick organisms is higher than a tolerable threshold. Running stochastic simulations, we study the interference of the adaptive movement survival strategy in spatial pattern formation, calculating the characteristic length scale of the typical spatial domains inhabited by organisms of each species. We compute how social distancing trigger impacts the chances of an individual being killed in the cyclic game and contaminated by the disease. The outcomes show that the species predominates in the cyclic game because of the organisms’ local adaptation. The territory occupied by the species grows with the proportion of individuals learning to trigger the social distancing tactic. We also show that organisms that perceive large distances more properly execute the adaptive strategy, promptly triggering the social distancing tactic and choosing the correct direction to move. Our findings may contribute to understanding the role of adaptive behaviour when environmental changes threaten biodiversity.
Drugs and Conditions That May Mimic Hemolysis
Authors: Jones Andrew D , Sapatnekar Suneeti , Bakdash Suzanne
Published: November 2022

Objectives

Visual inspection of posttransfusion plasma for hemolysis is a key laboratory method in the investigation of possible acute hemolytic transfusion reactions (AHTRs). Many substances and physiologic conditions can mimic hemolysis in vitro. Isolated reports describe specific cases of interference, but a comprehensive listing is lacking.

Methods

Using an illustrative case, we summarize available literature on substances and conditions that may mimic hemolysis in vitro. We further describe other substances and conditions that may discolor plasma but are unlikely to be mistaken for hemolysis on visual inspection.

Results

At least 11 substances and conditions have been reported to discolor plasma, in colors ranging from orange to red to brown, including relatively common therapies (eg, eltrombopag, hydroxocobalamin, iron dextran). Other substances are unlikely to be encountered in everyday practice but may mimic hemolysis in particular patient populations. Additional substances may cause plasma discoloration, ranging from blue to green to white, and are associated with a wide variety of therapies and conditions.

Conclusions

An awareness of the possible preanalytic confounding factors that may mimic hemolysis can aid in the workup of a suspected AHTR. Review of the medical record, use of ancillary testing, and consideration for nonimmune causes of hemolysis can aid in ruling out AHTR.
Developing the ‘Caring Being’ in Social Work: Reflections on my Grandmother’s Life
Authors: Pawar Manohar
Published: November 2022

The article is a personal story about my grandmother and how she experienced care in her old age. By sharing my grandmother’s life story about caring and reflecting on it, I inductively develop a thesis on caring and argue that caring is an asymmetrical phenomenon, and we can do better. The discussion includes the role of caring in social work practice and how to inculcate a focus on caring among workers so that they may contribute to creating caring communities. First, it exposes the complex phenomenon of dispossession at both personal and political levels and its implications for caring for elderly people. Secondly, it suggests the need for basic technology transfer. Thirdly, it points out the significance of emotional and material care and commitment to caring and challenges to sustaining it, and the need for innovations to enhance human caring. Fourthly, it emphasises the best interests of elderly people when choosing the place and space for caring arrangements. Finally, to creating caring communities, it suggests implications for integrating reason and emotion, and altering the professional values-base and policies. Social workers and similar professionals can contribute to caring communities to meet the challenging needs of growing ageing populations in the world.
Validation of ASCL1 and LHX8 Methylation Analysis as Primary Cervical Cancer Screening Strategy in South African Women with Human Immunodeficiency Virus
Authors: Vink Frederique J , Meijer Chris J L M , Lissenberg-Witte Birgit I , Visser Cathy , Duin Sylvia , Snyman Leon C , Richter Karin L , van der Merwe Frederick H , Botha Matthys H , Steenbergen Renske D M , Dreyer Greta
Published: November 2022

Background

Compared with women who are human immunodeficiency virus (HIV) negative, women with human immunodeficiency virus (WWH) have a higher human papillomavirus (HPV) prevalence and increased cervical cancer risk, emphasizing the need for effective cervical cancer screening in this population. The present study aimed to validate methylation markers ASCL1 and LHX8 for primary screening in a South African cohort of WWH.

Methods

In this post hoc analysis within the DIAgnosis in Vaccine And Cervical Cancer Screen (DiaVACCS) study, a South African observational multicenter cohort study, cervical scrape samples from 411 HIV-positive women were analyzed for hypermethylation of ASCL1 and LHX8 genes, HPV DNA, and cytology. Sensitivities, specificities, and positive and negative predictive values of primary methylation-based, HPV-based and cytology-based screening were calculated for the detection of cervical intraepithelial neoplasia of grade 3 or higher.

Results

Single markers ASCL1 and LHX8 resulted in a good performance for the detection of cervical intraepithelial neoplasia of grade 3 or higher, with sensitivities of 85.9% (95% confidence interval [CI], 78.2%–93.6%) and 89.7% (83.0%–96.5%), respectively, and specificities of 72.9% (67.3%–78.5%) and 75.0% (69.5%–80.5%). Combining markers ASCL1 and LHX8 resulted in a lower sensitivity compared with HPV testing (84.6% vs 93.6%, respectively; ratio, 0.90 [95% CI, .82–.99]) and a higher specificity (86.7% vs 78.3%; ratio 1.11 [1.02–1.20]) and reduced the referral rate from 46.8% to 33.4%. ASCL1/LHX8 methylation had a significantly higher sensitivity than cytology (threshold, high-grade intraepithelial squamous lesion or worse), (84.6% vs 74.0%, respectively; ratio, 1.16 [95% CI, 1.01–1.32]) and similar specificity (86.7% vs 91.0%; ratio, 0.95 [.90–1.003]).

Conclusions

Our results validate the accuracy of ASCL1/LHX8 methylation analysis for primary screening in WWH, which offers a full-molecular alternative to cytology- or HPV-based screening, without the need for additional triage testing.
The Geographic Distribution of Dimorphic Mycoses in the United States for the Modern Era
Authors: Mazi Patrick B , Sahrmann John M , Olsen Margaret A , Coler-Reilly Ariella , Rauseo Adriana M , Pullen Matthew , Zuniga-Moya Julio C , Powderly William G , Spec Andrej
Published: November 2022

Background

The dimorphic mycoses (DMs) of the United States—Histoplasma, Coccidioides, and Blastomyces—commonly known as endemic mycoses of North America (in addition to Paracoccidioides) are increasingly being diagnosed outside their historical areas of endemicity. Despite this trend, the maps outlining their geographic distributions have not been updated in more than half a century using a large, nationwide database containing individual-patient–level data.

Methods

This was a retrospective analysis of >45 million Medicare fee-for-service beneficiaries from 1 January 2007 through 31 December 2016. Diagnoses of histoplasmosis, coccidioidomycosis, and blastomycosis were defined by International Classification of Diseases, Ninth/10th Revision, codes. The primary outcome was the incidence of histoplasmosis, coccidioidomycosis, and blastomycosis for each US county. Clinically meaningful thresholds for incidence were defined as 100 cases/100 000 person-years for histoplasmosis and coccidioidomycosis and 50 cases/100 000 person-years for blastomycosis.

Results

There were 79 749 histoplasmosis, 37 726 coccidioidomycosis, and 6109 blastomycosis diagnoses in unique persons from 2007–2016 across 3143 US counties. Considering all US states plus Washington, DC, 94% (48/51) had ≥1 county above the clinically relevant threshold for histoplasmosis, 69% (35/51) for coccidioidomycosis, and 78% (40/51) for blastomycosis.

Conclusions

Persons with histoplasmosis, coccidioidomycosis, and blastomycosis are diagnosed in significant numbers outside their historical geographic distributions established >50 years ago. Clinicians should consider DM diagnoses based on compatible clinical syndromes with less emphasis placed on patients' geographic exposure. Increased clinical suspicion leading to a subsequent increase in DM diagnostic testing would likely result in fewer missed diagnoses, fewer diagnostic delays, and improved patient outcomes.
Adaptation in Outbred Sexual Yeast is Repeatable, Polygenic and Favors Rare Haplotypes
Authors: Linder Robert A , Zabanavar Behzad , Majumder Arundhati , Hoang Hannah Chiao-Shyan , Delgado Vanessa Genesaret , Tran Ryan , La Vy Thoai , Leemans Simon William , Long Anthony D
Published: November 2022

We carried out a 200 generation Evolve and Resequence (E&R) experiment initiated from an outbred diploid recombined 18-way synthetic base population. Replicate populations were evolved at large effective population sizes (>105 individuals), exposed to several different chemical challenges over 12 weeks of evolution, and whole-genome resequenced. Weekly forced outcrossing resulted in an average between adjacent-gene per cell division recombination rate of ∼0.0008. Despite attempts to force weekly sex, roughly half of our populations evolved cheaters and appear to be evolving asexually. Focusing on seven chemical stressors and 55 total evolved populations that remained sexual we observed large fitness gains and highly repeatable patterns of genome-wide haplotype change within chemical challenges, with limited levels of repeatability across chemical treatments. Adaptation appears highly polygenic with almost the entire genome showing significant and consistent patterns of haplotype change with little evidence for long-range linkage disequilibrium in a subset of populations for which we sequenced haploid clones. That is, almost the entire genome is under selection or drafting with selected sites. At any given locus adaptation was almost always dominated by one of the 18 founder's alleles, with that allele varying spatially and between treatments, suggesting that selection acts primarily on rare variants private to a founder or haplotype blocks harboring multiple mutations.
A molecular brake that modulates spliceosome pausing at detained introns contributes to neurodegeneration
Authors: Meng Dawei , Zheng Qian , Zhang Xue , Piao Xuejiao , Luo Li , Jia Yichang
Published: November 2022

Emerging evidence suggests that intron-detaining transcripts (IDTs) are a nucleus-detained and polyadenylated mRNA pool for cell to quickly and effectively respond to environmental stimuli and stress. However, the underlying mechanisms of detained intron (DI) splicing are still largely unknown. Here, we suggest that post-transcriptional DI splicing is paused at the B act state, an active spliceosome but not catalytically primed, which depends on Smad Nuclear Interacting Protein 1 (SNIP1) and RNPS1 (a serine-rich RNA binding protein) interaction. RNPS1 and B act components preferentially dock at DIs and the RNPS1 docking is sufficient to trigger spliceosome pausing. Haploinsufficiency of Snip1 attenuates neurodegeneration and globally rescues IDT accumulation caused by a previously reported mutant U2 snRNA, a basal spliceosomal component. Snip1 conditional knockout in the cerebellum decreases DI splicing efficiency and causes neurodegeneration. Therefore, we suggest that SNIP1 and RNPS1 form a molecular brake to promote spliceosome pausing, and that its misregulation contributes to neurodegeneration.
Anti-rituximab antibodies demonstrate neutralizing capacity, associate with lower circulating drug levels and earlier relapse in lupus
Authors: Wincup Chris , Dunn Nicky , Ruetsch-Chelli Caroline , Manouchehrinia Ali , Kharlamova Nastya , Naja Meena , Seitz-Polski Barbara , Isenberg David A , Fogdell-Hahn Anna , Ciurtin Coziana , Jury Elizabeth C
Published: November 2022

Objectives

High rates of anti-drug antibodies (ADA) to rituximab have been demonstrated in patients undergoing treatment for SLE. However, little is known with regard to their long-term dynamics, impact on drug kinetics and subsequent implications for treatment response. In this study, we aimed to evaluate ADA persistence over time, impact on circulating drug levels, assess clinical outcomes and whether they are capable of neutralizing rituximab.

Methods

Patients with SLE undergoing treatment with rituximab were recruited to this study (n = 35). Serum samples were collected across a follow-up period of 36 months following treatment (n = 114). Clinical and laboratory data were collected pre-treatment and throughout follow-up. ADA were detected via electrochemiluminescent immunoassays. A complement dependent cytotoxicity assay was used to determine neutralizing capacity of ADA in a sub-cohort of positive samples (n = 38).

Results

ADA persisted over the 36-month study period in 64.3% of patients undergoing treatment and titres peaked earlier and remained higher in those who had previously been treated with rituximab when compared with than those who were previously treatment naive. ADA-positive samples had a significantly lower median drug level until six months post rituximab infusion (P = 0.0018). Patients with persistent ADA positivity showed a significant early improvement in disease activity followed by increased rates of relapse. In vitro analysis confirmed the neutralizing capacity of ADA to rituximab.

Conclusions

ADA to rituximab were common and persisted over the 36-month period of this study. They associated with earlier drug elimination, an increased rate of relapse and demonstrated neutralizing capacity in vitro.
An Examination of Suicidal Behavior among Black College Students with Exposure to Police Violence
Authors: Szlyk Hannah , Motley Robert , Joe Sean , Nonas-Barnes Lucy , Azasu Enoch
Published: November 2022

There is limited research about suicidal behaviors among Black emerging adults (peak age of suicide risk) who report exposure to police violence. The current study applies an integrated approach to examine individual, immediate environment, and community-based risk and protective factors of suicide among Black college students who reported previous exposure to police violence. A purposive sample of Black college students (N = 300) was analyzed using bivariate analyses and binary logistic regression. Outcome variables investigated were lifetime suicidal ideation and suicide attempt. Twenty-eight percent of participants reported lifetime suicidal ideation and 14 percent reported lifetime attempts. Female students were significantly more likely to report lifetime suicidal ideation and recent symptoms of anxiety and to engage in emotional social support than male peers. Logistic regression results demonstrated that higher income and greater depression symptoms were associated with lower reporting of lifetime suicidal ideation. Reporting of more grit, the trait of perseverance and passion for long-term goals, was associated with a lower reporting of both lifetime suicidal ideation and suicide attempt. Findings have implications for how social workers in higher education are encouraged to address suicidal behavior among Black students, including the cultivation of grit.
Temperature-Dependent Growth and Spore Germination of Fungi Causing Grapevine Trunk Diseases: Quantitative Analysis of Literature Data
Authors: Ji Tao , Salotti Irene , Altieri Valeria , Li Ming , Rossi Vittorio
Published: November 2022

Grapevine trunk diseases (GTDs) are serious threats in all viticultural areas of the world, and their management is always complex and usually inadequate. Fragmented and inconsistent information on the epidemiology and environmental requirements of the causal fungi is among the reasons for poor disease control. Therefore, we conducted a quantitative analysis of literature data to determine the effects of temperature on mycelial growth and the effects of temperature and moisture duration on spore germination. Using the collected information, we then developed mathematical equations describing the response of mycelial growth to temperature, and the response of spore germination to temperature and moisture for the different species and disease syndromes. We considered 27 articles (selected from a total of 207 articles found through a systematic literature search) and 116 cases; these involved 43 fungal species belonging to three disease syndromes. The mycelial growth of the fungi causing Botryosphaeria dieback (BD) and the esca complex (EC) responded similarly to temperature, and preferred higher temperatures than those causing Eutypa dieback (ED) (with optimal temperature of 25.3, 26.5, and 23.3°C, respectively). At any temperature, the minimal duration of the moist period required for 50% spore germination was shorter for BD (3.0 h) than for EC (17.2 h) or ED (15.5 h). Mathematical equations were developed accounting for temperature–moisture relationships of GTD fungi, which showed concordance correlation coefficients ≥0.888; such equations should be useful for reducing the risk of infection.
Trends in outcomes of pregnancy in patients with congenital heart disease
Authors: Cutshall Andrew , Gourdine Ashlee , Bender Whitney , Karuppiah Arunthevaraja
Published: November 2022

Purpose of review

This review aims to analyze the trends in the management of pregnant patients with congenital heart disease (CHD).

Recent findings

The literature that this article reviews specifically highlights the importance of multidisciplinary and specialized care, the unique and variable physiologic differences within the umbrella of CHD in pregnancy, and recommendations for obstetric and anesthetic care in the prenatal and peripartum period.

The findings that this article summarizes have profound implications for clinical practice and management of the patient with CHD, including the optimization of preoperative screening, facilitation of ideal prenatal care to include qualified specialists and resources, and recommendations for optimal anesthetic management during labor and delivery.
Perceptions of motivating factors and barriers to precepting
Authors: Boyce Delaney J. , Shifrin Megan M. , Moses Shelley R. , Moss Colleen R.
Published: November 2022

Background:

Advanced practice registered nurses (APRNs) and physician assistants (PAs) are integral to health care delivery in the United States. However, the cultivation of APRNs and PAs relies heavily on the model of precepting. Advanced practice registered nurses and PAs frequently precept students or new hires, yet limited data are available to describe the motivations, incentives, and barriers associated with precepting.

Purpose:

The purpose of this mixed-method, cross-sectional study was to better understand APRN and PA preceptors' perceived levels of support during precepting, facilitating factors, and barriers to the precepting process.

Methods:

An electronic survey was distributed via REDCap to a convenience sample of APRN and PA preceptors at an academic medical center. Data collected from the survey were analyzed using both descriptive statistics and qualitative thematic analysis.

Results:

One hundred fifty-four participants completed the survey. Motivating factors for precepting included “giving back” to the profession, and barriers included inadequate time to precept while in the clinical role. Participants indicated that financial incentives, heightened communication, protected teaching time, preceptor training, meaningful recognition, and organizational support could enhance the precepting process.

Conclusion:

This study demonstrated that altruistic intentions frequently motivate APRN and PA preceptors, however, navigating multiple clinical responsibilities while precepting serves as a barrier to the precepting process. Preceptor training, ongoing education, dedicated time for precepting, enhanced communication, and organizational or professional incentives may optimize the APRN and PA precepting process.

Implications:

Further research should focus on how to optimally incorporate education, professional development, support, and incentives into the APRN and PA preceptor role.
Incidental Word Learning Through Multiple Media
Authors: Neuman Susan B. , Kaefer Tanya , Pinkham Ashley
Published: November 2022

Young children seem to pick up words quickly, almost effortlessly, through various media in the early years. Studies have shown that storybooks, TV, screen media, and ebooks can all be sources for incidental word learning without formal instruction. Yet, typically, research has investigated learning from a single medium in isolation or in comparison with another. In this article, we describe the potential for synergy—the combined use of multiple media platforms—and how the various symbol systems of these different media may support incidental word learning. We review recent eye-tracking studies that explore the formal features of a medium, its affordances and constraints, and suggest how multiple media might extend word-learning gains beyond those from a single medium alone. The article describes a theoretical mechanism to explain how these benefits might arise for word learning as well as implications for further research.
Preschool Teachers' Fidelity in Implementing a Vocabulary Intervention
Authors: Hadley Elizabeth Burke , Scott Molly , Foster Matthew E. , Dickinson David K. , Hirsh-Pasek Kathy , Golinkoff Roberta Michnick
Published: November 2022

This study examined preschool teachers' fidelity in implementing a vocabulary intervention. The purpose of the study is to inform the scaling up of vocabulary interventions, identifying strategies that are both feasible for teachers and effective for vocabulary learning. We analyzed data from a vocabulary intervention in which teachers (n = 10) taught 80 new target words to children (n = 138) during shared book reading (BR) and playful learning experiences (PLEs). Teachers were asked to use core intervention strategies, which included both teacher- and child-focused practices. Results showed that teachers had higher adherence to strategies in BR than in PLEs and for teacher-focused strategies versus child-focused practices. Across settings, teachers' use of core strategies and the use of child-focused practices were significantly related to children's vocabulary outcomes. Results not only suggest the importance of child-focused vocabulary teaching strategies but also indicate the need for additional coaching in this area for teachers.
Teacher–Child Conversations in Preschool
Authors: Hindman Annemarie H. , Farrow JeanMarie , Wasik Barbara A.
Published: November 2022

Back-and-forth conversations with adults are critical for developing children's language, and, therefore, an important part of the early childhood classroom learning environment; however, the specific nature of teacher feedback, one component of teacher–child conversations, on child language has not been widely studied. This article examined preschool teacher–child conversations during interactive book reading. We coded and analyzed the frequency and content of teacher talk, including feedback, among 20 teachers (11 who participated in a language and literacy intervention; 9 in business-as-usual instruction). Findings revealed that, particularly when teachers were guided on how to initiate and sustain intentional conversations, more conversations took place and were associated with higher overall classroom quality on a commonly used global assessment (the Classroom Assessment Scoring System); likewise, more teacher feedback occurred in intervention classrooms. The frequency of teacher feedback was uniquely linked to children's vocabulary learning on standardized measures beyond the effects of global classroom quality. Findings support the importance of understanding and supporting teacher feedback as an essential part of classroom conversations.
Long-Term Effects of Kindergarten Vocabulary Instruction and Intervention on Target Vocabulary Knowledge Through Second Grade
Authors: Coyne Michael D. , McCoach D. Betsy , Loftus-Rattan Susan M. , Baker Doris L. , Ware Sharon M.
Published: November 2022

We evaluated the long-term effects of a supplemental, small-group kindergarten vocabulary intervention in fall and spring of first grade and winter of second grade. Participants included students from two studies, an initial efficacy study and a subsequent replication study, identified as at risk for language and learning difficulties, who were randomly assigned in clusters to either a control group that received only classroom vocabulary instruction or a treatment group that received the classroom instruction plus small-group supplemental intervention. We also identified a group of not-at-risk students who received classroom vocabulary instruction as a reference group. Analyses using multilevel modeling indicated that students in the treatment group continued to outperform students in the control group on measures of expressive and receptive knowledge of words taught during the intervention through the winter of second grade, almost 2 years after the end of the intervention. Although long-term effects of the intervention on target word learning in second grade were substantial and meaningful, there was some deterioration of intervention effects across time. There were no effects of the kindergarten intervention on general vocabulary knowledge at posttest or any follow-up points. Findings suggest that the effects of direct and extended vocabulary instruction and intervention are generally durable and sustain over time for taught words.
Change in First-year Intravascular Ultrasound Results Predicts Adverse Events in Heart Transplant Recipients: Implications for Clinical Trial Endpoints
Authors: Seguchi Osamu , Azarbal Babak , Mirocha James , Youn Jong-Chan , Passano Elizabeth , Patel Jignesh , Kobashigawa Jon
Published: November 2022

Background.

Heart transplantation (HTx) is an established therapeutic option for patients with advanced heart failure who are refractory to conventional guideline-directed treatments. This study aimed to reassess whether intravascular ultrasound variables could predict adverse events after HTx in the modern era.

Methods.

One hundred primary HTx recipients with available serial intravascular ultrasound examination results of the left anterior descending artery 4–8 wk and 1 y after HTx were enrolled, with an average follow-up duration of 5.7 y. The primary endpoint was a composite of all-cause death, nonfatal major adverse cardiac events, and angiographic cardiac allograft vasculopathy.

Results.

Forty-three patients developed primary endpoints. The baseline maximal intimal thickness was independently associated with the primary endpoint (hazard ratio, 8.24; 95% confidential interval [CI], 3.21-21.21; P < 0.001), and the optimal cutoff value was 0.64 mm. A change in the plaque atheroma volume in a proximal 20-mm segment from the left anterior descending artery bifurcation >1.05 mm3/mm (hazard ratio, 2.75; 95% CI, 1.28-5.89; P = 0.009) and a change in the first-year maximal intimal thickness >0.27 mm (hazard ratio, 2.63; 95% CI, 1.05-6.56; P = 0.04) were independent predictors of the primary endpoint 1 y after intravascular ultrasonography.

Conclusions.

The aforementioned important clinical implications of intravascular ultrasound parameters are useful predictors of outcomes, which may be considered endpoints in modern clinical HTx trials.
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.

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.

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.

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.
Aestuarium zhoushanense is a later heterotypic synonym of Marivivens donghaensis, and transfer of Paradonghicola geojensis to the genus Marivivens as Marivivens geojensis comb. nov
Authors: Qu Luxuan , Li Yating , Wang Wanpeng , Shao Zongze , Gao Zheng , Lai Qiliang
Published: November 2022

The 16S rRNA genes of

Aestuarium zhoushanense

G7T and

Paradonghicola geojensis

FJ12T shared 100 % sequence identity with

Marivivens donghaensis

AM-4T. Phylogeny of 16S rRNA gene sequences showed that the three type strains formed a monophyletic clade within the genus

Marivivens

. Whole genome sequence comparisons showed that three type strains shared 46.7–69.7 % digital DNA–DNA hybridization, 92.1–96.4 % average nucleotide identity and 96.2–98.1 % average amino acid identity. The high 16S rRNA gene similarity values show that three type strains should belong to the same genus. The pan-genome of the five strains contained 5754 genes including 1877 core genes. Based on the principle of priority, we propose that

A. zhoushanense

Yu et al. 2019 is a later heterotypic synonym of

M. donghaensis

Park et al. 2016, and

P. geojensis

should be reclassified as Marivivens geojensis comb. nov., respectively.
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

The 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

Recent 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

Encoding 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.