bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Analysis Reveals Relationships Among Populations of Puccinia striiformis f. sp. tritici from Shaanxi–Gansu–Ningxia–Xinjiang of Northwestern and Sichuan–Yunnan of Southwestern China
Authors: Zhang Zhuoyue , Fu Yanzi , Huang Jie , Peng Yunliang , Zhou Xinli , Gao Haifeng , Wang Baotong , Li Qiang
Published: December 2023

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most destructive diseases worldwide. In China, wheat stripe rust generally occurs in the northwestern and southwestern regions; however, the genetic relationships of Pst populations between these regions are largely unclear. To determine the population structure and potential migration route in these regions, 235 isolates collected from Xinjiang (XJ), Gansu (GS), Ningxia (NX), Shaanxi (SX), Sichuan (SC), and Yunnan (YN) provinces in 2021 and 2022 were phenotyped using two sets of Pst differentials and genotyped using 20 competitive allele-specific PCR–single nucleotide polymorphism (KASP-SNP) markers. The phenotype tests indicated that CYR34, CYR32, and CYR33 were the predominant races with different occurrence frequencies in different regions and years. Genotypic analysis revealed that a total of 183 multilocus genotypes were identified, and the genetic diversity in the YN subpopulation was the highest. The genetic background in the SX subpopulation was similar to that in the GS and NX subpopulations, and the genetic background in the YN subpopulation was similar to that in the SC and SX subpopulations. A high level of gene flow (Nm) was found between the SX and GS, SX and NX, GS and NX, and SC and YN subpopulations, suggesting the migration of Pst among these regions, while a small amount of Nm existed between the SX and SC subpopulations. SC may serve as a bridge connecting Pst subpopulations between the northwestern provinces (SX, GS, and NX) and the southwestern provinces (SC and YN). With a relatively high genetic distance and low Nm values compared with other Pst subpopulations, XJ is considered a relatively independent epidemiological region in China. These results improved our current understanding of the wheat stripe rust epidemic in northwestern and southwestern regions of China.
Multistate Sensitivity Monitoring of Fusarium virguliforme to the SDHI Fungicides Fluopyram and Pydiflumetofen in the United States
Authors: Hamilton Ryan , Jacobs Janette L. , McCoy Austin G. , Kelly Heather M. , Bradley Carl A. , Malvick Dean K. , Rojas J. Alejandro , Chilvers Martin I.
Published: December 2023

Sudden death syndrome (SDS), caused by Fusarium virguliforme, is an important yield-limiting disease of soybean (Glycine max). From 1996 to 2022, cumulative yield losses attributed to SDS in North America totaled over 25 million metric tons, which was valued at over US $7.8 billion. Seed treatments are widely used to manage SDS by reducing early season soybean root infection by F. virguliforme. Fluopyram (succinate dehydrogenase inhibitor [SDHI] – FRAC 7), a fungicide seed treatment for SDS management, has been registered for use on soybean in the United States since 2014. A baseline sensitivity study conducted in 2014 evaluated 130 F. virguliforme isolates collected from five states to fluopyram in a mycelial growth inhibition assay and reported a mean EC50 of 3.35 mg/liter. This baseline study provided the foundation for the objectives of this research: to detect any statistically significant change in fluopyram sensitivity over time and geographical regions within the United States and to investigate sensitivity to the fungicide pydiflumetofen. We repeated fluopyram sensitivity testing on a panel of 80 historical F. virguliforme isolates collected from 2006 to 2013 (76 of which were used in the baseline study) and conducted testing on 123 contemporary isolates collected from 2016 to 2022 from 11 states. This study estimated a mean absolute EC50 of 3.95 mg/liter in isolates collected from 2006 to 2013 and a mean absolute EC50 of 4.19 mg/liter in those collected in 2016 to 2022. There was no significant change in fluopyram sensitivity (P = 0.1) identified between the historical and contemporary isolates. A subset of 23 isolates, tested against pydiflumetofen under the same conditions, estimated an absolute mean EC50 of 0.11 mg/liter. Moderate correlation was detected between fluopyram and pydiflumetofen sensitivity estimates (R = 0.53; P < 0.001). These findings enable future fluopyram and pydiflumetofen resistance monitoring and inform current soybean SDS management strategies in a regional and national context.
A Classic in Nursing
Authors: Kirton Carl A.
Published: December 2023

Celebrating the life and work of Barbara Braden
Utilizing Artificial Intelligence and Chat Generative Pretrained Transformer to Answer Questions About Clinical Scenarios in Neuroanesthesiology
Authors: Blacker Samuel N. , Kang Mia , Chakraborty Indranil , Chowdhury Tumul , Williams James , Lewis Carol , Zimmer Michael , Wilson Brad , Lele Abhijit V.
Published: December 2023

Objective:

We tested the ability of chat generative pretrained transformer (ChatGPT), an artificial intelligence chatbot, to answer questions relevant to scenarios covered in 3 clinical guidelines, published by the Society for Neuroscience in Anesthesiology and Critical Care (SNACC), which has published management guidelines: endovascular treatment of stroke, perioperative stroke (Stroke), and care of patients undergoing complex spine surgery (Spine).

Methods:

Four neuroanesthesiologists independently assessed whether ChatGPT could apply 52 high-quality recommendations (HQRs) included in the 3 SNACC guidelines. HQRs were deemed present in the ChatGPT responses if noted by at least 3 of the 4 reviewers. Reviewers also identified incorrect references, potentially harmful recommendations, and whether ChatGPT cited the SNACC guidelines.

Results:

The overall reviewer agreement for the presence of HQRs in the ChatGPT answers ranged from 0% to 100%. Only 4 of 52 (8%) HQRs were deemed present by at least 3 of the 4 reviewers after 5 generic questions, and 23 (44%) HQRs were deemed present after at least 1 additional targeted question. Potentially harmful recommendations were identified for each of the 3 clinical scenarios and ChatGPT failed to cite the SNACC guidelines.

Conclusions:

The ChatGPT answers were open to human interpretation regarding whether the responses included the HQRs. Though targeted questions resulted in the inclusion of more HQRs than generic questions, fewer than 50% of HQRs were noted even after targeted questions. This suggests that ChatGPT should not currently be considered a reliable source of information for clinical decision-making. Future iterations of ChatGPT may refine algorithms to improve its reliability as a source of clinical information.
Implementation of a Nurse-Driven Eat-Sleep-Console (ESC) Treatment Pathway at a Community Hospital for Treatment of Neonatal Opioid Withdrawal Syndrome in an Effort to Improve Short-term Outcomes
Authors: Halloum Hamza , Daniels Brooke J. , Beville Dawn , Thrasher Kathleen , Martin Gregory C. , Ellsworth Marc A.
Published: December 2023

Background:

The Chandler Regional Medical Center (CRMC) neonatal intensive care unit (NICU) began a phased implementation of Eat-Sleep-Console (ESC) for the management of those at risk for neonatal opioid withdrawal syndrome (NOWS).

Purpose:

The purpose of this initiative is to track short-term outcomes as well as the program's effect on nursing workflow and job performance rating/satisfaction.

Methods:

A retrospective review of the ESC implementation process at CRMC from the years 2018-2020. The study consisted of 3 epochs: (1) traditional pharmacologic management; (2) parent-led ESC management; and (3) parent/nurse-led ESC management. Length of stay (LOS), treatment pathway assignment, and proportion of infants treated with pharmacologic agents were compared between epochs. In addition, a survey of NICU nursing staff was distributed to measure nurses' perceptions and attitudes towards the ESC program and the management of infants with NOWS.

Results:

The proportion of infants treated via ESC increased (0%, 53%, and 100%), with an associated decrease in LOS (18.4, 10.5, and 9.3 days) during each epoch of the study period. Thirty-seven nurses completed the survey, with 94% of nurses reporting being comfortable caring for ESC patients and 89% feeling supported in their ESC nursing assignments, with only 11% stating that caring for ESC patients significantly alters their other nursing care processes.

Implications for Practice and Research:

Implementation of an ESC treatment program for infants with NOWS significantly decreased LOS and the proportion of infants treated pharmacologically. This phased implementation process was not associated with self-reported negative nursing perceptions of the program and its treatment goals/outcomes.
Patterns of radiological response to tebentafusp in patients with metastatic uveal melanoma
Authors: Roshardt Prieto Natalia M. , Turko Patrick , Zellweger Caroline , Nguyen-Kim Thi Dan Linh , Staeger Ramon , Bellini Elisa , Levesque Mitchell P. , Dummer Reinhard , Ramelyte Egle
Published: December 2023

Metastatic uveal melanoma (mUM) is a rare type of melanoma with poor outcomes. The first systemic treatment to significantly prolong overall survival (OS) in patients with mUM was tebentafusp, a bispecific protein that can redirect T-cells to gp-100 positive cells. However, the objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) may underestimate the clinical impact of tebentafusp. As metabolic response assessed by PET Response Criteria in Solid Tumors (PERCIST) has been reported to better correlate with clinical outcome, we here compared the patterns of radiological and morphological responses in HLA-A*02:01-positive patients with mUM treated with tebentafusp. In the 19 enrolled patients, RECIST showed an overall response rate (ORR) of 10%, median progression-free survival of 2.8 months (95% CI 2.5–8.4), and median OS (mOS) of 18.8 months. In 10 patients, where both RECIST and PERCIST evaluation was available, the ORR was 10% for both; however, the PFS was longer for PERCIST compared to RECIST, 3.1 and 2.4 months, respectively. A poor agreement between the criteria was observed at all assessments (Cohen’s kappa ≤0), yet they differed significantly only at the first on-treatment imaging (P = 0.037). Elevated baseline LDH and age were associated with an increased risk for RECIST progression, while lymphocyte decrease after the first infusions correlated to reduced risk of RECIST progression. Detectable ctDNA at baseline did not correlate with progression. Early response to tebentafusp may be incompletely captured by conventional imaging, leading to a need to consider both tumor morphology and metabolism.
Clinical Practice Guidelines for Managing Genitourinary Symptoms Associated With Menopause
Authors: Christmas Monica , Huguenin Annabelle , Iyer Shilpa
Published: December 2023

Genitourinary syndrome of menopause encompasses the group of urogenital signs and symptoms resultant from hypoestrogenism, including genital dryness, burning or irritation, sexual discomfort, pain or dysfunction, and urinary urgency, dysuria, and recurrent urinary tract infections. Genitourinary syndrome of menopause can have a profound impact on well-being, functioning, and quality of life in postmenopausal women. Treatment includes vaginal moisturizers and lubricants geared towards providing symptomatic relief; hormonal treatments which promote epithelial thickening and production of vaginal secretions; and pelvic floor physical therapy along with behavioral therapies that address pelvic floor hypertonicity and psychosocial factors.
Dynamic regulation of EXO1 promotes the progression from liver fibrosis to HCC through TGF-β1/Smad signaling feedback loop
Authors: Li Mengting , Huang Fengxing , Zhu Weining , Peng Yanan , Xu Fei , Li Wenjie , Zhao Qiu , Liu Lan
Published: December 2023

Background:

HSCs are the main stromal cells in the process of liver fibrosis and accelerate HCC progression. Previous studies determined that highly expressed exonuclease 1 (EXO1) increases the malignant behavior of HCC cells and is closely related to liver cirrhosis. This study aimed to explore the roles and mechanisms of EXO1 in the development of liver cirrhosis and HCC.

Methods:

We fully demonstrated that EXO1 expression was positively correlated with liver fibrosis and cirrhotic HCC by combining bioinformatics, hepatic fibrosis mouse models, and human HCC tissues. The role of EXO1 in a murine HCC model induced by activated forms of AKT and Ras oncogenes (AKT/Ras) was investigated by employing an adeno-associated virus-mediated EXO1 knockdown technique.

Results:

The knockdown of EXO1 promoted a regression of HCC in AKT/Ras mice and reduced the degree of liver fibrosis. Downregulated EXO1 inhibited LX-2 cell activation and inhibited the proliferation and migration of HCC cells. Moreover, conditioned medium of LX-2 cells with EXO1 overexpression increased the proliferation and migration of HCC cells, which was attenuated after EXO1 knockout in LX-2 cells. EXO1 knockdown attenuated the role of LX-2 in promoting HepG2 xenograft growth in vivo. Mechanistically, EXO1 promotes the activation of the downstream TGF-β-smad2/3 signaling in LX-2 and HCC cells. Interestingly, increased TGF-β-smad2/3 signaling had a feedback effect on EXO1, which sustains EXO1 expression and continuously stimulates the activation of HSCs.

Conclusions:

EXO1 forms a positive feedback circuit with TGF-β-Smad2/3 signaling and promotes the activation of HSCs, which accelerates HCC progression. Those findings indicate EXO1 may be a promising target for the diagnosis and treatment of cirrhotic HCC.
Aging aggravates liver fibrosis through downregulated hepatocyte SIRT1-induced liver sinusoidal endothelial cell dysfunction
Authors: Dai Qingqing , Qing Xin , Jiang Wei , Wang Shouwen , Liu Shengsheng , Liu Xuesheng , Huang Fan , Zhao Hongchuan
Published: December 2023

Background:

Aging increases the susceptibility to chronic liver diseases and hastens liver fibrosis deterioration, but the underlying mechanisms remain partially understood. The aim of this study was to investigate the effect of aging and chronic liver diseases on hepatocyte Sirtuin 1 (SIRT1) and LSECs and their contribution to liver fibrosis pathogeneses.

Methods:

Young (8–12 wk) and aged (18–20 mo) mice were subjected to carbon tetrachloride–induced liver fibrosis. Primary HSCs and LSECs were isolated and cocultured for in vitro experiments. Liver tissues and blood samples from healthy controls and patients with liver fibrosis were analyzed.

Results:

Downregulated hepatocytes SIRT1 in aged mice increased high mobility group box 1 acetylation, cytoplasmic translocation, and extracellular secretion, causing LSECs dysfunction by means of the toll-like receptor 4/AK strain transforming (AKT)/endothelial nitric oxide synthase pathway, ultimately activating HSCs and increasing susceptibility to liver injury and fibrosis. Adeno-associated virus-mediated overexpression of SIRT1 in hepatocytes suppressed the abovementioned alterations and attenuated carbon tetrachloride–induced liver injury and fibrosis in liver fibrosis mice, and there were no significant differences in liver injury and fibrosis indicators between young and aged mice after SIRT1 overexpression treatment. In vitro experiments demonstrated that SIRT1 overexpression and endothelial nitric oxide synthase agonist YC-1 improved LSECs function and inhibited HSCs activation, mediated by nitric oxide. Similarly, downregulated hepatocytes SIRT1 and LSECs dysfunction were observed in the livers of aged individuals compared to young individuals and were more pronounced in aged patients with liver fibrosis.

Conclusions:

Aging aggravates liver fibrosis through downregulated hepatocytes SIRT1-induced LSECs dysfunction, providing a prospective curative approach for preventing and treating liver fibrosis.
Risk of HCC decreases in HBV-related patients with cirrhosis acquired recompensation: A retrospective study based on Baveno VII criteria
Authors: Zhang Yiheng , Liu Xu , Li Shu , Lin Chunlei , Ye Qian , Wang Yuying , Wu Juanli , Zhang Yushuang , Gao Han , Li Tao , Qu Yundong , Wang Yan
Published: December 2023

Background:

Antiviral therapy improves the clinical outcomes of patients with HBV-related cirrhosis. In this study, we aimed to evaluate the incidence rate of HCC in patients with HBV-related recompensated, compensated, or decompensated cirrhosis based on the latest Baveno VII criteria.

Methods:

In this two-center retrospective study, HBV-related patients with cirrhosis were enrolled and treated with first-line nucleos(t)ide analogues therapy for at least 12 months. Participants were classified into 3 groups: (1) compensated group, (2) decompensated group, or (3) recompensated group according to Baveno VII criteria. Multivariate regression models and propensity score matching were used to identify the predictors of HCC.

Results:

Of the 404 patients recruited, during a median follow-up of 44.5 months (interquartile range 26.8, 57.0 months), 233 (57.7%), 100 (24.8%), and 71(17.6%) patients had compensated, recompensated, and decompensated cirrhosis. In total, 38 developed HCC. The cumulative incidence of HCC development at 2, 4, and 6 years was 1.3%, 5.4%, and 20.0% in the compensated group, 1.2%, 5.2%, and 24.5% in the recompensated group, and 2.1%, 23.6%, and 41.8% in the decompensated group, respectively. In the multivariate Cox regression model, compared with the recompensated group, the decompensated group had a significant increased risk for the development of HCC (aHR 2.55; 95% CI: 1.240–5.240; p = 0.027), while the compensated group had similar HCC risk for the development of HCC (aHR 1.41; 95% CI: 0.540–3.730; p = 0.835). Propensity score-matching analysis between the recompensated and compensated groups (84 pairs) and propensity score-matching analysis between the recompensated and decompensated groups (62 pairs) showed similar results.

Conclusions:

Achieving recompensation reduced the risk of HCC in patients with HBV-related decompensated cirrhosis, while the risk remained comparable to that of compensated cirrhosis.
Descemet Membrane Endothelial Keratoplasty: 10-Year Cell Loss and Failure Rate Compared With Descemet Stripping Endothelial Keratoplasty and Penetrating Keratoplasty
Authors: Price Marianne O. , Kanapka Lauren , Kollman Craig , Lass Jonathan H. , Price Francis W.
Published: December 2023

Purpose:

The aim of this study was to assess long-term endothelial cell loss (ECL) and graft failure with Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping endothelial keratoplasty (DSEK) versus penetrating keratoplasty (PK) performed for the same indications (primarily Fuchs dystrophy and pseudophakic corneal edema) in the Cornea Donor Study.

Methods:

This retrospective study included consecutive primary DMEK (529 recipients, 739 eyes) and DSEK cases (585 recipients, 748 eyes) with 1 or more endothelial cell density (ECD) measurements at 6 months to 16 years. Main outcomes were ECD, longitudinal ECL, and graft failure.

Results:

Between 6 months and 8 years the ECD declined linearly by approximately 118 cells/mm2/yr after DMEK and 112 cells/mm2/yr after DSEK. Beyond 8 years postoperatively the rate of decline slowed substantially. Selective dropout from graft failure did not significantly affect the ECD trend. At 10 years, median ECL (interquartile range) was 63% (45, 73) with DMEK, 68% (48, 78) with DSEK, and 76% (70, 82) with PK (P = 0.01 DMEK vs. DSEK, P <0.001 DMEK vs. PK, and P < 0.001 DSEK vs. PK). The proportion of surviving grafts with 10-year ECD <500 cells/mm2 was 1.4% with DMEK, 7.3% with DSEK, and 23.9% with PK. The cumulative risk of graft failure between 6 months and 10 years was 5% with DMEK, 11% with DSEK, and 19% with PK (P < 0.001).

Conclusions:

Compared with PK and DSEK, DMEK had significantly lower ECL and significantly lower risk of secondary graft failure through 10 years.
Front-Line Health Care Workers’ COVID-19 Infection Contamination Risks: A Human Factors and Risk Analysis Study of Personal Protective Equipment
Authors: Doos Devin , Hughes Ashley M. , Pham Trang , Barach Paul , Bona Anna , Falvo Lauren , Moore Malia , Cooper Dylan D. , Ahmed Rami
Published: December 2023

Infectious risks escalate with complex donning and doffing personal protective equipment (PPE) protocols. Recent studies suggest that PPE donning and doffing behaviors that deviate from protocol during PPE reuse compounded the risks of health care worker (HCW) self-contamination. This study quantified the occurrence of behaviors associated with known risks in PPE use and reuse. We conducted a prospective study of emergency department HCWs and video-recorded PPE donning and doffing 5 times in simulated patient encounters. Trained coders recorded HCW behaviors according to an evidence-based guide. All 28 participants deviated from the Centers for Disease Control and Prevention (CDC) sanctioned donning and doffing protocol order, and most were documented to have (92.85%) self-contaminated at least once during each simulated clinical encounter. Behaviors that compounded self-contamination due to PPE reuse were also observed. Wide variation in PPE donning and doffing behaviors was found among front-line, experienced HCWs. Future work is needed to determine which deviations put HCWs at increased risk for accidental self-contamination and what changes are needed to the CDC protocol for protecting HCW from infections.
Efficacy of continuous arterial perfusion chemotherapy combined with transarterial chemoembolization regional arterial thermal perfusion in the treatment of pancreatic cancer with liver metastases
Authors: Zhong Zhuo , Yang Jian , Luo Jing-Zi , Xie Xiong , Huang Zhi-Mei , Long De
Published: December 2023

Background

The aim of the study was to investigate the efficacy of continuous transcatheter arterial infusion chemotherapy combined with transarterial chemoembolization (TACE) for the treatment of advanced pancreatic cancer with liver metastasis.

Methods

Sixty patients with advanced pancreatic cancer and liver metastases were enrolled in this study. In the treatment group, 31 patients underwent continuous transcatheter arterial infusion chemotherapy combined with TACE regional arterial thermal perfusion, whereas 29 patients included in the control group received intravenous chemotherapy with gemcitabine and S-1. All patients received maintenance chemotherapy with S-1 after 4 cycles of the study regimen. Treatment efficacy, quality of life, survival, and toxicity were evaluated.

Results

Efficacy was better in the treatment group than in the control group, as reflected by the objective remission, partial remission, and disease progression rates (all P < 0.05). The Eastern Cooperative Oncology Group and Numerical Rating Scale pain scores were also higher in the treatment group (both P < 0.05). In survival analysis, the 1-year overall survival rates in the treatment and control groups were 64.516% and 10.345%, respectively, whereas the median overall survival times were 16 and 6 months, respectively (both P < 0.05). The 6-month progression-free survival rates in the treatment and control groups were 77.419% and 13.790%, respectively, and the median progression-free survival times were 12 and 3 months, respectively (both P < 0.05). The rates of hematological and nonhematological toxicological adverse effects were also lower in the treatment group (both P < 0.05). Although the rate of liver dysfunction was higher in the treatment group, this finding had no adverse effects on prognosis.

Conclusions

Continuous transcatheter arterial infusion chemotherapy combined with TACE regional arterial perfusion chemotherapy resulted in better efficacy and safety outcomes in patients with pancreatic cancer and liver metastasis, suggesting its utility as a reference method for the clinical treatment of advanced pancreatic cancer.
Assessing transmission attribution risk from simulated sequencing data in HIV molecular epidemiology
Authors: Nascimento Fabrícia F. , Mehta Sanjay R. , Little Susan J. , Volz Erik M.
Published: December 2023

Background:

HIV molecular epidemiology (ME) is the analysis of sequence data together with individual-level clinical, demographic, and behavioral data to understand HIV epidemiology. The use of ME has raised concerns regarding identification of the putative source in direct transmission events. This could result in harm ranging from stigma to criminal prosecution in some jurisdictions. Here we assessed the risks of ME using simulated HIV genetic sequencing data.

Methods:

We simulated social networks of men-who-have-sex-with-men, calibrating the simulations to data from San Diego. We used these networks to simulate consensus and next-generation sequence (NGS) data to evaluate the risks of identifying direct transmissions using different HIV sequence lengths, and population sampling depths. To identify the source of transmissions, we calculated infector probability and used phyloscanner software for the analysis of consensus and NGS data, respectively.

Results:

Consensus sequence analyses showed that the risk of correctly inferring the source (direct transmission) within identified transmission pairs was very small and independent of sampling depth. Alternatively, NGS analyses showed that identification of the source of a transmission was very accurate, but only for 6.5% of inferred pairs. False positive transmissions were also observed, where one or more unobserved intermediaries were present when compared to the true network.

Conclusion:

Source attribution using consensus sequences rarely infers direct transmission pairs with high confidence but is still useful for population studies. In contrast, source attribution using NGS data was much more accurate in identifying direct transmission pairs, but for only a small percentage of transmission pairs analyzed.
Exercise interventions for frail older adults with cancer
Authors: Sattar Schroder , Haase Kristen R. , Lee Kayoung , Campbell Kristin L.
Published: December 2023

Purpose of review

Frailty is prevalent in older adults with cancer and can lead to complications during cancer treatment and poor health outcomes. Exercise has been shown to be a promising strategy to mitigate frailty and slow the accumulation of functional impairment in the general geriatric population. In this review, we present a discussion on the state of the science of exercise interventions for frail older adults with cancer. This review is timely and relevant given the aging of the population and corresponding increase in proportion of older adults living with cancer.

Recent findings

Existing research related to exercise interventions for frail older adults with cancer appear to show some promise in feasibility and efficacy in both surgical and systemic treatment settings.

More research on this topic and testing rigorously structured exercise interventions for older adults with cancer may help inform cancer-specific guidelines and create a foundation of evidence to enable implementation of exercise interventions. These interventions can support cancer care to attenuate frailty-related outcomes while extending its benefit to overall health of this population.
Optic Nerve Sheath Meningiomas: A National Surveillance, Epidemiology, and End Results (SEER) Database Analysis
Authors: Hussain Zain S. , Loya Asad , Riaz Kamran M. , Lee Andrew G.
Published: December 2023

Background:

Optic nerve sheath meningioma (ONSM) is a rare optic nerve cancer with considerable morbidity. This national analysis validates previously known ONSM concepts while providing insight into novel risk factors.

Methods:

The Surveillance, Epidemiology, and End Results (SEER) Program was queried from 2000 to 2019 for all histologic subtypes of meningioma primary to the optic nerve. Relevant clinical and demographic variables were analyzed. Asymptotic one-sample test for binomial proportions and Cox proportional hazards modeling evaluated the significance of factor associations.

Results:

A total of 51 ONSM cases were extracted. A greater proportion of cases were observed in females (N = 37, 73%, P < 0.001) and individuals with age 50 years or more (N = 29, 57%, P < 0.001); the mean number of months from diagnosis to treatment was 4.6 months (SD 4.1, range 13). Psychosocial epidemiologic parameter analysis demonstrated a greater proportion of patients with married status on diagnosis (N = 31, 61%, P < 0.001), listed total family income between $55,000 and $74,999 (N = 24, 47%, P < 0.001). Relative to cases diagnosed clinically only, cases diagnosed radiologically without microscopic confirmation experienced decreased all-cause mortality (HR = 0.041, P = 0.050).

Conclusions:

Our SEER national analysis affirms previously characterized ONSM concepts. Upon ONSM diagnosis and if needed, treatment protocols are not significantly delayed. Novel psychosocial factors for ONSM were identified, including marital status, total family income, and non-Hispanic white race. Additional ONSM diagnostics may reduce longitudinal mortality burden.
Training in cortically-blind fields confers patient-specific benefit against retinal thinning after occipital stroke
Authors: Fahrenthold Berkeley K. , Cavanaugh Matthew R. , Tamhankar Madhura , Lam Byron L. , Feldon Steven E. , Johnson Brent A. , Huxlin Krystel R.
Published: December 2023

Purpose

Damage to the adult primary visual cortex (V1) causes vision loss in the contralateral hemifield, initiating a process of trans-synaptic retrograde degeneration (TRD). Here, we examined retinal correlates of TRD using a new metric to account for global changes in inner retinal thickness, and asked if perceptual training in the intact or blind field impacts its progression.

Methods

We performed a meta-analysis of optical coherence tomography (OCT) data in 48 participants with unilateral V1 stroke and homonymous visual defects, who completed clinical trialNCT03350919. After measuring the thickness of the macular ganglion cell and inner plexiform layers (GCL-IPL), and the peripapillary retinal nerve fiber layer (RNFL), we computed individual laterality indices (LI) at baseline and after ∼6 months of daily motion discrimination training in the intact- or blind-field. Increasingly positive LI denoted greater layer thinning in retinal regions affectedversusunaffected by the cortical damage.

Results

Pre-training, the affected GCL-IPL and RNFL were thinner than their unaffected counterparts, generating LI values positively correlated with time since stroke. Participants trained in their intact-field exhibited increased LIGCL-IPL. Those trained in their blind-field had no significant change in LIGCL-IPL. LIRNFLdid not change in either group.

Conclusions

Relative shrinkage of the affectedversusunaffected macular GCL-IPL can be reliably measured at an individual level and increases with time post-V1 stroke. Relative thinning progressed during intact-field training, but appeared to be halted by training within the blind field, suggesting a potentially neuroprotective effect of this simple behavioral intervention.
Structural elucidation of how ARF small GTPases induce membrane tubulation for vesicle fission
Authors: Pang Xiaoyun , Zhang Yan , Park Kunyou , Liao Zhenyu , Li Jian , Xu Jiashu , Hong Minh-Triet , Yin Guoliang , Zhang Tongming , Wang Yaoyu , Egelman Edward H. , Fan Jun , Park Seung-Yeol , Hsu Victor W. , Sun Fei
Published: December 2023

The ADP-Ribosylation Factor (ARF) small GTPases have been found to act in vesicle fission through a direct ability to tubulate membrane. Here, we have used cryo-electron microscopy (EM) to solve the structure of an ARF6 protein lattice assembled on tubulated membrane to 3.9 Å resolution. ARF6 forms tetramers that polymerize into helical arrays to form this lattice. We identify, and confirm functionally, protein contacts critical for this lattice formation. The solved structure also suggests how the ARF amphipathic helix is positioned in the lattice for membrane insertion, and how a GTPase-activating protein (GAP) docks onto the lattice to catalyze ARF-GTP hydrolysis in completing membrane fission. As ARF1 and ARF6 are structurally conserved, we have also modeled ARF1 onto the ARF6 lattice, which has allowed us to pursue the reconstitution of Coat Protein I (COPI) vesicles to confirm more definitively that the ARF lattice acts in vesicle fission. Our findings are notable for having achieved the first detailed glimpse of how a small GTPase bends membrane and having provided a molecular understanding of how an ARF protein acts in vesicle fission.
AnArabidopsisSR protein relieving ABA inhibition of seedling establishment represses ABA-responsive alternative splicing
Authors: Laloum Tom , Martín Guiomar , Lewinski Martin , Yanez Romana J. R. , Köster Tino , Staiger Dorothee , Duque Paula
Published: December 2023

The phytohormone abscisic acid (ABA) inhibits postgerminative growth under unfavorable conditions to delay the transition to the autotrophic stage and promote plant survival. While stress-induced ABA accumulation is well established to trigger extensive transcriptional changes, it is becoming clear that it also relies on alternative splicing to enhance stress tolerance. However, the upstream components modulating posttranscriptional regulation of the ABA response remain largely unknown. Here, we show that loss of function of theArabidopsisSR34a protein enhances sensitivity to ABA during seedling establishment. Individual-nucleotide crosslinking and immunoprecipitation (iCLIP) combined with RNA-sequencing revealed that SR34a is an alternative splicing regulator that binds predominantly GCU-rich exonic sequences near splice sites. We find that SR34a targets all alternative splicing event types, including in RNAs encoding known determinants of ABA sensitivity, to prevent ABA-responsive splicing in germinated seeds. Our study sheds mechanistic light on how plant SR proteins regulate alternative splicing and counteract ABA inhibition of early plant growth.
Task-Dependent Representation of Feature Binding within the Same Dimension in Visual Working Memory
Authors: Cao Ruoyi , Deouell Leon Y.
Published: December 2023

Working memory (WM) serves as a neurocognitive system responsible for temporarily storing and manipulating information when its source has disappeared. Previous investigations into whether features within the same dimension were stored separately or conjoined into objects have yielded conflicting findings. Based on increasing evidence on the adaptivity of the working memory system, we conjectured that the format in which objects from the same dimension are stored in Visual Working Memory (VWM) might be contingent on the specific task demands, and subtle distinctions across experiments may account for the disparities in results. In the current study, we introduced modifications to the paradigm used by Luck and Vogel (1997) and Wheeler and Treisman (2002), where the same paradigm led to different conclusions, to assess whether implicit task requirements could influence the storage format of objects in visual working memory. In two conditions, we manipulated the relevance of conjunction between two colors by varying the proportions of Mis-conjunct probes, a probe type depending on conjunction information for accurate responses. The results showed that in both conditions, performance was primarily determined by the number of features rather than the number of objects, aligning with the results of Wheeler and Treisman. Nevertheless, we observed that Mis-conjunct probes, which require conjunction information, exhibited improved performance when tested more frequently. This suggests that the format of retention in working memory, whether in separate or conjoined form, is influenced by the task demands.
Inverse folding of protein complexes with a structure-informed language model enables unsupervised antibody evolution
Authors: Shanker Varun R. , Bruun Theodora U.J. , Hie Brian L. , Kim Peter S.
Published: December 2023

Large language models trained on sequence information alone are capable of learning high level principles of protein design. However, beyond sequence, the three-dimensional structures of proteins determine their specific function, activity, and evolvability. Here we show that a general protein language model augmented with protein structure backbone coordinates and trained on the inverse folding problem can guide evolution for diverse proteins without needing to explicitly model individual functional tasks. We demonstrate inverse folding to be an effective unsupervised, structure-based sequence optimization strategy that also generalizes to multimeric complexes by implicitly learning features of binding and amino acid epistasis. Using this approach, we screened ∼30 variants of two therapeutic clinical antibodies used to treat SARS-CoV-2 infection and achieved up to 26-fold improvement in neutralization and 37-fold improvement in affinity against antibody-escaped viral variants-of-concern BQ.1.1 and XBB.1.5, respectively. In addition to substantial overall improvements in protein function, we find inverse folding performs with leading experimental success rates among other reported machine learning-guided directed evolution methods, without requiring any task-specific training data.
BioLLMBench: A Comprehensive Benchmarking of Large Language Models in Bioinformatics
Authors: Sarwal Varuni , Munteanu Viorel , Suhodolschi Timur , Ciorba Dumitru , Eskin Eleazar , Wang Wei , Mangul Serghei
Published: December 2023

Large Language Models (LLMs) have shown great promise in their knowledge integration and problem-solving capabilities, but their ability to assist in bioinformatics research has not been systematically evaluated. To bridge this gap, we present BioLLMBench, a novel benchmarking framework coupled with a scoring metric scheme for comprehensively evaluating LLMs in solving bioinformatics tasks. Through BioLLMBench, we conducted a thorough evaluation of 2,160 experimental runs of the three most widely used models, GPT-4, Bard and LLaMA, focusing on 36 distinct tasks within the field of bioinformatics. The tasks come from six key areas of emphasis within bioinformatics that directly relate to the daily challenges and tasks faced by individuals within the field. These areas are domain expertise, mathematical problem-solving, coding proficiency, data visualization, summarizing research papers, and developing machine learning models. The tasks also span across varying levels of complexity, ranging from fundamental concepts to expert-level challenges. Each key area was evaluated using seven specifically designed task metrics, which were then used to conduct an overall evaluation of the LLM’s response. To enhance our understanding of model responses under varying conditions, we implemented a Contextual Response Variability Analysis. Our results reveal a diverse spectrum of model performance, with GPT-4 leading in all tasks except mathematical problem solving. GPT4 was able to achieve an overall proficiency score of 91.3% in domain knowledge tasks, while Bard excelled in mathematical problem-solving with a 97.5% success rate. While GPT-4 outperformed in machine learning model development tasks with an average accuracy of 65.32%, both Bard and LLaMA were unable to generate executable end-to-end code. All models faced considerable challenges in research paper summarization, with none of them exceeding a 40% score in our evaluation using the Recall-Oriented Understudy for Gisting Evaluation (ROUGE) score, highlighting a significant area for future improvement. We observed an increase in model performance variance when using a new chatting window compared to using the same chat, although the average scores between the two contextual environments remained similar. Lastly, we discuss various limitations of these models and acknowledge the risks associated with their potential misuse.
Understanding the Easterlin Paradox in China: Investigating the Psychological Stress and its Relation to Nonincome Factors
Authors: Zeng Zhaoying , Chen Youqing , Su Wenliang
Published: December 2023

Although China’s economy and living conditions have improved significantly in the past few decades, previous studies have found that residents’ happiness has not kept pace with them accordingly. Such an Esterlin paradox may partly be due to the increase in psychological stress in the progress of China’s urbanization. To verify this point, we constructed an index of psychological stress (IPS) through daily internet search queries of four psychological stress-related keywords obtained from the Baidu Index from 2011 to 2021. The IPS for each province, municipality, and main city during 2018-2019 was also calculated. Meanwhile, the city level’s economic factors (GDP per capita, income of employees), living costs (housing prices, commuting time), and living environment quality (air quality, environmental noise) were employed to predict the IPS. The results showed that the IPS in China showed an upward trend from 2011 to 2021, and it was higher in the eastern coastal regions than in other regions. Housing prices and commuting time were the only significant predictors of IPS in the hierarchical regression. Our results suggested that the Easterlin paradox in China may be explained by the rising IPS linked with higher living expenses in the course of urbanization.
Predictors of COVID-19 Vaccine Hesitancy in North-Central Nigeria
Authors: Olutola Ayodotun , Gobir Ibrahim Bola , Bazira Deus , Agboola Samson , Sanni Fatimah Ohunene , Bello Azeez Akanbi , Nnadozie Havilah Onyinyechi , Adamu Aisha , Bello Fatima , Otubo Suzzy Angmun , Nyang Mercy Piring’ar
Published: December 2023

COVID-19 vaccine hesitancy has emerged as a major challenge to global efforts to control the pandemic, particularly in Nigeria, where hesitancy to other effective vaccines such as polio and measles has been widely reported. Several individual, societal, and structural factors contribute to this behaviour and prevent the effectiveness of COVID-19 prevention efforts.

Objectives

This study sought to assess the factors associated with COVID-19 vaccine hesitancy in the six states of north-central Nigeria.

Methods

A population-based cross-sectional online survey was conducted among residents using a semi-structured questionnaire adapted from the WHO SAGE vaccine hesitancy scale and distributed via social media networks over 8-weeks.

Results

A total of 1,999 responses were received, of which 570 were set aside comprising 512 respondents that resided outside the study area, 12 respondents that reported no knowledge of the COVID-19 vaccine, and 46 entries with missing data. Of 1,429 included in the analysis, 1,008 (70.5%) were willing to be vaccinated and/or already vaccinated and 421 (29.5%) were unwilling to receive the COVID-19 vaccine. Post-secondary education (AOR: 0.51, 0.37-0.69), household income above the minimum wage of 30,000 Naira per month (AOR: 0.68, 0.50-0.94) and people of the Islamic faith (AOR: 0.69, 0.53-0.90) were found to be associated with lower levels of hesitancy. The dominant reasons for hesitancy were concerns about side effects (37.5%), doubt about the existence of COVID-19 (11.0%), and the perception of time required to receive the vaccine (9.6%). Hesitant respondents relied on health workers (33.0%) and social media (23.3%) as their trusted sources of health information, and less than a third (31.4%) followed the advice of their religious and community leaders.

Conclusion

All three factors of confidence, complacency and convenience influenced hesitancy in our study. Socioeconomic factors are major drivers of hesitancy. Therefore, hesitancy is as much a social issue as health and requires a multisectoral approach to educating communities and building trust in health and social institutions.
“Endless Opportunities”: A qualitative exploration of facilitators and barriers to scale-up of two-way texting follow-up after voluntary medical male circumcision in Zimbabwe
Authors: Elkins Chelsea , Kokera Sandra B. , Vumbugwa Phiona , Gavhera Jacqueline , West Kathleen M. , Wilson Katherine S. , Makunike-Chikwinya Batsirai , Masimba Lewis , Holec Marianne , Barnhart Scott , Matinu Sulemana , Wassuna Beatrice , Feldacker Caryl
Published: December 2023

In Zimbabwe, the ZAZIC consortium employs two-way, text-based (2wT) follow-up to strengthen post-operative care for voluntary medical male circumcision (VMMC). 2wT scaled nationally with evidence of client support and strengthened follow-up. However, 2wT uptake remains suboptimal. Understanding the gap between mobile health (mHealth) potential for innovation expansion and scale-up realization is critical for 2wT and other mHealth innovations. Therefore, we conducted an exploratory qualitative study with the objective of identifying 2wT program strengths, challenges, and suggestions for scale up as part of routine VMMC services. A total of 16 in-depth interviews (IDIs) with diverse 2wT stakeholders were conducted, including nurses, monitoring & evaluation teams, and technology partners – a combination of perspectives that provide new insights. We used both inductive and deductive coding for thematic analysis. Among 2wT drivers of expansion success, interviewees noted: 2wT care benefits for clients; effective hands-on 2wT training; ease of app use for providers; 2wT saved time and money; and 2wT strengthened client/provider interaction. For 2wT scale-up challenges, staff shortages; network infrastructure constraints; client costs; duplication of paper and electronic reporting; and complexity of digital tools integration. To improve 2wT robustness, respondents suggested: more staff training to offset turnover; making 2wT free for clients; using 2wT to replace paper VMMC reporting; integrating with routine VMMC reporting systems; and expanding 2wT to other health areas. High stakeholder participation in app design, implementation strengthening, and evaluation were appreciated. Several 2wT improvements stemmed from this study, including enrollment of multiple people on one number to account for phone sharing; 2wT inclusion of minors ages 15+; clients provided with $1 to offset SMS costs; and reduced SMS messages to clients. Continued 2wT mentoring for staff, harmonization of 2wT with Ministry e-health data systems, and increased awareness of 2wT’s client and provider benefits will help ensure successful 2wT scale-up.
Chemical genetic interaction linking eIF5A hypusination and mitochondrial integrity
Authors: Matsumoto Ken , Kurokawa Rumi , Takase Megumi , Schneider-Poetsch Tilman , Ling Feng , Suzuki Takehiro , Han Peixun , Wakigawa Taisei , Suzuki Masato , Tariq Mohammad , Ito Akihiro , Higashi Kyohei , Iwasaki Shintaro , Dohmae Naoshi , Yoshida Minoru
Published: December 2023

The eukaryotic translation factor eIF5A plays an important role in translation elongation, especially across stretches of prolines and charged amino acids, and in translation termination. eIF5A undergoes hypusination, a post-translational modification unique to this protein, although the role of hypusination in the function of eIF5A remains elusive. Here, we investigated the cellular defects induced by the hypusination inhibitor GC7 (N1-guanyl-1,7-diaminoheptane). Proteome, translatome, and transcriptome analyses indicated that GC7 downregulated a subset of mitochondrial proteins and DNA, causing mitochondrial stress and eliciting the integrated stress response. Chemical genomic screening using barcoded shRNA libraries identified genes encoding proteins involved in polyamine metabolism/transport andMPV17L2, a mitochondrial disease gene homologue whose product regulates mitochondrial translation. Depletion of MPV17L2 caused hypersensitivity to GC7 and phenocopied the effects of GC7 treatment. These results suggest that eIF5A hypusination and MPV17L2 synthetically regulate mitochondrial molecular synthesis and integrity.