bluuebunny/crossref_metadata_2025 huggingface dataset:
Roles of Ear Injury, Infestation, and Vector Activity by Ostrinia furnacalis (Asian Corn Borer) and Conogethes punctiferalis (Yellow Peach Moth) in Fusarium verticillioides Infection and Kernel Fumonisin Level
Authors: Li Qincheng , Shi Jie , Huang Chaolong , Guo Jingfei , Hellmich Richard L. , He Kanglai , Wang Zhenying
Published: May 2023

Field experiments were conducted to evaluate the roles of two corn borers, Asian corn borer (ACB), Ostrinia furnacalis and yellow peach moth (YPM), Conogethes punctiferalis, in Fusarium verticillioides infection using green fluorescent protein (GFP) as a marker. Effects of insect injury, manual injury, and insecticide application on fumonisin production also were assessed. In this study, third instars of ACB and YPM significantly increased GFP-tagged F. verticillioides infection compared with the control, regardless of the fungal inoculation method. Besides acquiring F. verticillioides spores from leaf surfaces and transmitting them to ears, larvae of the ACB and YPM also injure maize ears, which allows F. verticillioides from leaves or silk to infect ears more easily. This suggests that ACB and YPM larvae are vectors of F. verticillioides, which can increase the occurrence of ear rot. Manual injuries significantly increased GFP-tagged F. verticillioides infection of ears, while effective insect control significantly reduced F. verticillioides infection of ears. Insecticide control of borers also significantly reduced fumonisin content in kernels. Larval infestations significantly increased fumonisins in kernels to levels higher than or very close to the European Union threshold (4,000 μg kg−1). Significant and high correlations among corn borer attack, F. verticillioides severity, and kernel fumonisin levels were discovered, confirming the important role of ACB and YPM activity in F. verticillioides infection and kernel fumonisin production.
Effect of hyperthermic intraperitoneal chemotherapy on survival and recurrence rates in advanced gastric cancer: a systematic review and meta-analysis
Authors: Patel Maitreyi , Arora Amandeep , Mukherjee Dipankar , Mukherjee Samrat
Published: May 2023

Background:

Around 5–20% of patients who undergo surgery for advanced gastric cancer (AGC), which invades into the muscularis propria or beyond, have peritoneal carcinomatosis. The peritoneal recurrence rate is 10–54%, which is associated with a poor prognosis. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) in AGC with and without peritoneal carcinomatosis is not clearly defined.

Methods:

The authors conducted a meta-analysis, in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, of the clinical trials and high-quality nonrandomized studies evaluating the role of HIPEC in AGC over the last 10 years. The studies were searched in PubMed, EMBASE, MEDLINE, and Cochrane databases between January 2011 to December 2021. Clinical data including overall survival, recurrence free survival, overall recurrence rate, peritoneal recurrence rate, and complications analyzed using RevMan 5.4.

Results:

Six randomized controlled trials and 10 nonrandomized studies, comprising a total of 1700 patients were included. HIPEC was associated with significantly improved OS at 3 [odd ratio (OR) 1.89, 95% CI: 1.17–3.05] and 5 years (OR 1.87, 95% CI: 1.29–2.71). HIPEC was associated with reduced overall recurrence (OR 0.49, 95% CI: 0.31–0.80) and peritoneal recurrence (OR 0.22, 95% CI: 0.11–0.47). HIPEC was not associated with increased complications. The occurrence of postoperative renal dysfunction was significantly higher in the HIPEC group (OR 3.94, 95% CI: 1.85–8.38).

Conclusion:

The role of HIPEC in AGC has evolved over the past decade. HIPEC may improve survival rates and reduce recurrence rates in patients with AGC, without significant increase in complications and with a favorable impact on 3 and 5-year survival.
Potential of nanoemulsions for accelerated wound healing: innovative strategies
Authors: Chhabra Jatin , Chopra Hitesh , Pahwa Rakesh , Raina Neha , Wadhwa Karan , Saini Swati , Negi Poonam , Gupta Madhu , Singh Inderbir , Dureja Harish , Emran Talha Bin
Published: May 2023

Wounds represent various significant health concerns for patients and also contribute major costs to healthcare systems. Wound healing comprises of overlapped and various coordinated steps such as homeostasis, inflammation, proliferation, and remodeling. In response to the failure of many strategies in delivering intended results including wound closure, fluid loss control, and exhibiting properties such as durability, targeted delivery, accelerated action, along with histocompatibility, numerous nanotechnological advances have been introduced. To understand the magnitude of wound therapy, this systematic and updated review discussing the effectiveness of nanoemulsions has been undertaken. This review portrays mechanisms associated with wound healing, factors for delayed wound healing, and various technologies utilized to treat wounds effectively. While many strategies are available, nanoemulsions have attracted the tremendous attention of scientists globally for the research in wound therapy due to their long-term thermodynamic stability and bioavailability. Nanoemulsions not only aid in tissue repair, but are also considered as an excellent delivery system for various synthetic and natural actives. Nanotechnology provides several pivotal benefits in wound healing, including improved skin permeation, controlled release, and stimulation of fibroblast cell proliferation. The significant role of nanoemulsions in improved wound healing along with their preparation techniques has also been highlighted with special emphasis on mechanistic insights. This article illustrates recent research advancements for the utilization of nanoemulsions in wound treatment. An adequate literature search has been conducted using the keywords ‘Nanoemulsions in wound healing’, ‘Wound therapy and nanoemulsions’, ‘Herbal actives in wound therapy’, ‘Natural oils and wounds treatment’ etc., from PubMed, Science Direct, and Google Scholar databases. Referred and original publications in the English language accessed till April 2022 has been included, whereas nonEnglish language papers, unpublished data, and nonoriginal papers were excluded from the study.
Learning curve in pipeline embolization device: results from the pipeline embolization device in china post-market multi-center registry study
Authors: Lu Junlin , Zhao Yang , Zhang Hongqi , Li Tianxiao , Song Donglei , Sheng Guan , Maimaitili Aisha , Wang Yunyan , Feng Wenfeng , Wang Yang , Wan Jieqing , Mao Guohua , Shi Huaizhang , Yang Xinjian , Liu Jianmin , Zhao Yuanli
Published: May 2023

Background:

Intracranial aneurysms pose a significant health issue, affecting 3–5% of the adult population. The pipeline embolization device (PED) has emerged as a promising treatment for these lesions. This study aimed to investigate the impact of operator experience on complication and poor outcome rates, as well as the learning curve for PED.

Methods:

A total of 217 patients were consecutively enrolled from four eligible centers and divided into three groups based on the number of procedures performed: group 1 (first ten procedures), group 2 (11–20 procedures), and group 3(>20 procedures). Major complications include operation-related ischemic or hemorrhagic events and mass effect deterioration. Poor outcome was defined as a modified Rankin Scale score > 2 at discharge. Cumulative summation (CUSUM) analysis was generated to assess the learning curve according to major complications and poor outcome.

Results:

The study found that major complications and poor outcomes occurred in 5.1% and 2.3% of cases, respectively. The rate of major complications decreased from 10.0% in group 1 to 2.9% in group 3 (P=0.053), while the rate of poor outcomes decreased from 7.5% in group 1 to 0.7% in group 3 (P=0.015). Multivariable regression analysis adjusted for covariates showed that operator experience was associated with a lower rate of poor outcomes (P=0.034). CUSUM analysis demonstrated that the learning curve for avoiding major complications and poor outcomes required 27 (mean=13) and 40 (mean=20) cases, respectively.

Conclusions:

Our findings suggest that PED treatment requires a learning curve of 40 cases to achieve reproducibility regarding complications and functional results. Additionally, major complications and poor outcomes significantly decreases after the first 20 procedures. CUSUM analysis can serve as a useful tool for monitoring and assessing surgical performance.
A Novel ANO1 Gene Variant is Associated with Intestinal Dysmotility Syndrome Masquerading as Hirschsprung Disease: A Case Report
Authors: Al Sharie Ahmed H. , Abu Mousa Balqis M. , Al Zu’bi Yazan O. , Al Qudah Mohammad A. , Jaradat Saied A. , Barakat Ahmad , Altamimi Eyad
Published: May 2023

Anoctamin 1 (ANO1)-related intestinal dysmotility syndrome (OMIM: 620045) is an extremely rare disorder with only 2 cases reported in the medical literature. We present the clinical scenario of a 2-month-old male infant that presented to our center with diarrhea, vomiting, and abdominal distension. Routine investigations did not yield a clear diagnosis. Whole-exome sequencing showed a novel homozygous nonsense ANO1 pathogenic variant (c.1273G>T) with a protein alternation of p.Glu425Ter that fits the patient’s phenotype. Sanger sequencing revealed the same ANO1 variant in both parents in a heterozygous form confirming an autosomal recessive mode of inheritance. The patient experienced multiple bouts of diarrhea-related metabolic acidosis, dehydration, and severe electrolyte imbalances that required intensive care unit monitoring. The patient was managed conservatively and being followed regularly in an outpatient setting.
The Experiences of Older Adults Living With Inflammatory Bowel Disease
Authors: Rohatinsky Noelle , Russell Brooke , Read Kevin B.
Published: May 2023

The prevalence of inflammatory bowel disease is rising in persons older than 65 years. Although there is extensive literature on inflammatory bowel disease in older adults from a disease-related outcome, epidemiological, and treatment perspective, the older adult perspective on inflammatory bowel disease-related care needs and experiences is not well represented. This scoping review examines the existing literature regarding the care experiences of older adults living with inflammatory bowel disease. A systematic search was conducted using 3 concepts: older adults, inflammatory bowel disease, and patient experience. Seven publications met the inclusion criteria. Reported data include study design and methods, sample characteristics, and findings relevant to the research question. Two themes were identified: preferences for interactions with healthcare personnel and peer support networks, and barriers to accessing care for inflammatory bowel disease needs. An overarching concept across all studies was the need and request for individualized, patient-centered care where patient preferences are considered. This review highlights the need for more research on the older adult age group to guide evidence-informed practice that meets their individual inflammatory bowel disease care needs.
An Evaluation of an Advanced Practice Provider Led Weight Intervention in Liver Disease (WILD) Pathway
Authors: Repking Sarah , Mayer Karen , Folkers Colleen , Shah Vicki , Janardhan Sujit
Published: May 2023

Within the scope of their practice, advanced practice providers provide similar patient care as physicians, but in some cases have outperformed physicians in terms of health outcomes, satisfaction, and cost-effectiveness. At an academic medical center, hepatology trained advanced practice providers, who were also certified in obesity management, led an interprofessional team to develop the Weight Intervention in Liver Disease pathway. In September 2018, patients who were seen in the hepatology practice and met criteria for enrollment were referred to the Weight Intervention in Liver Disease program for comprehensive care of obesity and related metabolic disorders. A program evaluation was conducted in 2021 to identify whether the effectiveness of the advanced practice provider-led structure and process, and the Weight Intervention in Liver Disease pathway, supported weight loss goals as well as improvement in alanine aminotransferase levels, patient satisfaction, and provider satisfaction. Results found that the structure of the pathway and the implementation are resulting in positive outcomes of 100% patient satisfaction, 80% provider satisfaction, and a total average sustained weight loss of 5.05% (SD = 7.98, p < .01). A weight loss pathway led by trained advanced practice providers proves successful in long-term weight loss goals.
Exercise prehabilitation for patients with end-stage liver disease: a best practice implementation project
Authors: Gao Bingxin , Zhao Wenwen , Su Wei , Qiu Jie , Xi Huan , Li Na , Zhang Yuxia
Published: May 2023

Objectives:

This study aimed to promote exercise prehabilitation in patients with end-stage liver disease during their waiting period for liver transplantation.

Introduction:

End-stage liver disease indirectly contributes to the development of sarcopenia and affects survival after liver transplantation because of low physiological reserves and insufficient aerobic capacity while awaiting transplantation. Exercise prehabilitation could reduce postoperative complications and promote postoperative recovery.

Methods:

Following the JBI Practical Application of Clinical Evidence System, this study used six audit criteria derived from the JBI Evidence Summary. A baseline audit of six patients and nine nurses was conducted, analyzed barriers, established a prehabilitation process and improved interventions, followed by the implementation of exercise prehabilitation and follow-up audit.

Results:

In the baseline audit, the results of the six criteria [(1) multimodal prehabilitation that includes exercise and other interventions where appropriate is offered to patients scheduled for abdominal surgery; (2) prior to the commencement of an exercise program an assessment of exercise contraindications, health status, treatments, physical activity level, functional capacity and quality of life is completed; (3) exercise programs are designed by appropriately qualified personnel; (4) exercise is delivered and supervised by appropriately qualified personnel; (5) exercise prescription is tailored to each individual patient; and (6) patient response to exercise is monitored throughout prehabilitation] were 0–22%. After implementing the best-practice strategies, all six criteria were set to 100%. Patients were aware of and had high compliance with exercise prehabilitation, nurses’ and patients’ knowledge of exercise rehabilitation improved, and nurses’ implementation rate was significantly higher than before implementation (P < 0.05). The differences in the 6 min walking distance and Borg Fatigue Score between the preimplementation and postimplementation were statistically significant (all P < 0.05).

Conclusions:

This best-practice implementation project is feasible. These results indicate that exercise prehabilitation could improve the preoperative walking capacity and fatigue of patients with end-stage liver disease. Ongoing best practices will be expected to develop in the future.
A potent CD8 T-cell response may be associated with partial cross-protection conferred by an attenuated Chinese HP-PRRSV vaccine against NADC30-like PRRSV challenge
Authors: Li Shuai , Li Jiaqi , Tian Yunfei , Liu Jiawei , Zhu Jianzhong , Chen Nanhua , Shang Shaobin
Published: May 2023

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating pathogens to the global swine industry. Many commercial PRRSV vaccines, originally designed to provide homologous protection, have shown partial protection against heterologous strains. However, the protective immune mechanisms mediated by these PRRSV vaccines are not fully understood. In this study, we investigated the factors responsible for partial protection conferred by an attenuated Chinese HP-PRRSV vaccine (TJM-F92) against heterologous NADC30-like PRRSV. By analysing peripheral T-cell responses induced by the TJM-F92 vaccine and local and systemic memory responses following challenge with NADC30-like PRRSV (SD17-38 strains) as well as neutralizing antibody response, we found that the TJM-F92 vaccine induced a significant expansion of CD8 T cells but not CD4 T cells or γδ T cells. The expanded CD8 T cells exhibited a phenotype of effector memory T cells and secreted IFN-γ upon restimulation with SD17-38 strains in vitro. In addition, only CD8 T cells in the prior immunized pigs rapidly expanded in the blood and spleen after heterologous challenge, with higher magnitude, compared to the unvaccinated pigs, showing a remarkable memory response. In contrast, no obvious humoral immune response was enhanced in the vaccinated and challenged pigs, and no heterologous neutralizing antibodies were detected throughout the experiment. Our results suggested that CD8 T cells elicited by the TJM-F92 vaccine may be responsible for partial heterologous protection against NADC30-like PRRSV strains and potentially recognize the conserved antigens among PRRSV strains.
Genomic SEM Applied to Explore Etiological Divergences in Bipolar Subtypes
Authors: Lawrence Jeremy M. , Breunig Sophie , Foote Isabelle F. , Tallis Connor B. , Grotzinger Andrew D.
Published: May 2023

Background

Bipolar Disorder (BD) is an overarching diagnostic class defined by the presence of at least one prior manic episode (BD I) or both a prior hypomanic episode and a prior depressive episode (BD II). Traditionally, BD II has been conceptualized as a less severe presentation of BD I, however, extant literature to investigate this claim has been mixed.

Methods

We apply Genomic Structural Equation Modeling (Genomic SEM) to investigate divergent genetic pathways across BD’s two major subtypes using the most recent GWAS summary statistics from the PGC. We begin by identifying divergences in genetic correlations across 89 external traits using a Bonferroni corrected threshold. We also use a theoretically informed follow-up model to examine the extent to which the genetic variance in each subtype is explained by schizophrenia and major depression. Lastly, Transcriptome-wide SEM (T-SEM) was used to identify gene expression patterns associated with the BD subtypes.

Results

BD II was characterized by significantly larger genetic overlap with internalizing traits (e.g., neuroticism, insomnia, physical inactivity), while significantly stronger associations for BD I were limited. Consistent with these findings, the follow-up model revealed a much larger major depression component for BD II. T-SEM results revealed 41 unique genes associated with risk pathways across BD subtypes.

Conclusions

Divergent patterns of genetic relationships across external traits provide support for the distinction of the bipolar subtypes. However, our results also challenge the illness severity conceptualization of BD given stronger genetic overlap across BD II and a range of clinically relevant traits and disorders.
Vaccine effectiveness of BNT162b2 mRNA Covid-19 Vaccine in Children below 5 Years in German Primary Care
Authors: Strumann Christoph , Ranzani Otavio , Moor Jeanne , Berner Reinhard , Töpfner Nicole , Chao Cho-Ming , Moor Matthias B.
Published: May 2023

Background

Despite the approval of BNT162b2 mRNA vaccine for children aged 6 months to 4 years by the European Medicines Agency (EMA) and the Federal Drug Administration (FDA) in 2022, no data on vaccine effectiveness (VE) of BNT162b2 are available in this age group. We here report on the VE of BNT162b2 during an Omicron BA.1-2 dominant period.

Methods

An authentication-based retrospective survey was performed between April 14th 2022 and May 9th 2022 in individuals that had registered children for off-label SARS-CoV-2 vaccination in Germany. We used Cox regression to estimate relative VE of two BNT162b2 doses, with the period between first and second vaccine dose as reference period (24.8+-0.6 days) and >=7 days after Dose 2 to before Dose 3 as post-vaccination period (59.5+-23.6 days).

Results

The present analysis included 4615 children aged 2.8+-1.2 years (mean+-standard deviation) who had received their first dose of BNT162b2 on January 1st 2022 or thereafter. VE was substantial for protection from any SARS-CoV-2 infection (VE: 53.1% [95% confidence interval (CI): 36.3-69.6%], p<0.001), symptomatic SARS-CoV-2 infections (VE: 57.5% [95% CI: 40.8-74.2%], p<0.001), and SARS-CoV-2 infections leading to medication use (VE: 66.2% [95% CI: 43.7-88.7%], p<0.001). Differences in dosage of BNT162b2 yielded no change in VE.

Conclusion

This study offers a first industry-independent insight in the potential VE of two doses of the BNT162b2 vaccine in children aged below 5 years, as currently only immunogenicity data by the manufacturer Pfizer/BioNTech are available. Limitations include the retrospective study design, and that the reported VE does not necessarily correspond to currently circulating SARS-CoV-2 variants.
Discontinuation of Heart Failure Therapy in patients Undergoing Non-Cardiac surgery: Data from a Real-world Cohort
Authors: Elharram Malik , Wang Xiaoming , Gouda Pishoy , Graham Michelle M.
Published: May 2023

Background and Aims

Patients with heart failure (HF) with reduced ejection fraction (HFrEF) are at high risk for cardiovascular events following non-cardiac surgery. The perioperative period represents many challenges to maintain guideline directed medical therapy (GDMT). We examined GDMT use in HFrEF patients following non-cardiac surgery, and the association of medication changes with cardiovascular outcomes.

Methods

Using linked administrative databases, a retrospective cohort of HFrEF patients undergoing major non-cardiac surgery between 2008 and 2020 was formed. Pre-operative use of GDMT was determined by outpatient prescriptions up to 90 days prior to surgery. Changes in GDMT was defined as discontinuation or a dose reduction (≥50%) of baseline therapies at 90 days after discharge. The primary composite outcome was HF hospitalization or all-cause mortality at one-year adjusted for age, sex, components of the Revised Cardiac Risk Index and the Charlson Comorbidity index.

Results

Of 397,829 index surgeries, there were 7667 (2%) patients with pre-existing HFrEF on at least one GDMT (50.6% female; mean age: 75 +/- 12 years). At 90 days post-operatively, 46% of patients had undergone major changes to GDMT. Compared to patients who continued GDMT, patients with any change to therapy had a higher incidence of the primary outcome (52% vs. 46%, aOR: 1.14, 95% CI: 1.03-1.25) and all-cause mortality at one year (8.5% vs. 4.9%, aOR: 1.57, 95% CI: 1.3-1.90).

Conclusion

Among patients with HFrEF undergoing major non-cardiac surgery, few are on optimal GDMT, and perioperative changes to GDMT is associated with higher odds for HF hospitalization or death.
Pretreatment Identification of 90-Day Readmission Among Heart Failure Patients Receiving Aquapheresis Treatment
Authors: Alkhatib Deya , Karabayir Ibrahim , Pour-Ghaz Issa , Khan Sania , Hart Linda , Cease Megan , Jefferies John L , Akbilgic Oguz
Published: May 2023

BACKGROUND

The use of traditional models to predict heart failure (HF) has limitations in preventing HF hospitalizations. Artificial intelligence (AI) and machine learning (ML) in cardiovascular medicine only have limited data published regarding HF populations, with none assessing the favorability of decongestive therapy aquapheresis (AQ). AI and ML can be leveraged to design non-traditional models to identify those who are at high risk of HF readmissions.

OBJECTIVES

This study aimed to develop a model for pretreatment identification of risk for 90-day HF events among HF patients who have undergone AQ.

METHODS

Using data from the AVOID-HF (Aquapheresis versus Intravenous Diuretics and Hospitalization for Heart Failure) trial, we designed a ML-based predictive model that can be used before initiating AQ to anticipate who will respond well to AQ and who will be at high risk of future HF events.

RESULTS

Using ML we identified the top ten predictors for 90-day HF events. Interestingly, the variable for ‘intimate relationships with loved ones’ strongly predicted response to therapy. This ML-model was more successful in predicting the outcome in HF patients who were treated with AQ. In the original AVOID-HF trial, the overall 90-day HF event rate in the AQ arm was 32%. Our proposed predictive model was accurate in anticipating 90-day HF events with better statistical accuracy (area under curve 0.88, sensitivity 80%, specificity 75%, negative predictive value 90%, and positive predictive value 57%).

CONCLUSIONS

ML can help identify HF patients who will respond to AQ therapy. Our model can identify super-respondents to AQ therapy and predict 90-day HF events better than currently existing traditional models.

CONDENSED ABSTRACT

Utilizing data from the AVOID-HF trial, we designed a ML-predictive model that can be used before initiating AQ to anticipate who will respond well to AQ and who will be at high risk of future HF events. Using ML, we identified the top 10 predictors for 90-day HF events. Our model can identify super-respondents to ultrafiltration therapy and predict 90-day HF events better than currently existing traditional models.
Short term effect of tetrahydrocurcumin on adipose angiogenesis in very high-fat diet-induced obesity mouse model
Authors: Yoysungnoen Bhornprom , Srisawat Umarat , Piyabhan Pritsana , Sookprasert Nattapon , Duansak Naphatsanan , Mathuradavong Nakorn , Poomipark Natwadee , Munkong Narongsuk , Changtam Chatchawan
Published: May 2023

Tetrahydrocurcumin (THC) has been shown to possess anti-angiogenic activities. This study aims to investigate the effects of THC on adipose angiogenesis and expression of angiogenic factors that occurs in 60% high-fat diet-induced obese mice. Male ICR mice were randomly divided into 3 groups: mice fed with a low-fat diet (LFD group); mice fed with very high fat diet (VHFD group), and mice fed with VHFD supplemented with THC (300 mg/kg/day orally)(VHFD+THC group) for 6 weeks. Body weight (BW), food intake, fasting blood sugar (FBS), lipid profiles and visceral fats weight (VF) were measured. The microvascular density (MVD), VEGF, MMP-2 and MMP-9 expressions were evaluated. The VHFD group had significantly increased total cholesterol, triglyceride, food intake, BW, VF, VF/BW ratio, adipocyte size and the number of crown-liked structures as compared to LFD group. THC supplementation markedly reduced these parameters and adipocyte hypertrophy and inflammation in white adipose tissues. MVD, VEGF, MMP-2 and MMP-9 were over-expressed in the VHFD group. However, THC supplementation decreased MVD and reduced expression of VEGF, MMP-2 and MMP-9. In conclusion, THC suppressed angiogenesis in adipose tissue by the downregulation of VEGF, MMP-2 and MMP-9. With its effects on lipid metabolism as well as on food consumption, THC could contribute to lower visceral fat and body weight. Overall, our study demonstrated the potential benefit of THC in mitigating obesity and associated metabolic disorders along with elucidated the suppression of adipose angiogenesis as one of its underlying mechanisms.

Author summary

Conceptualization, B.Y, U.S., P.P., N.D., N.S. and N.M3.; methodology, B.Y., U.S., P.P., N.D., N.S., N.M3., and C.C; validation, B.Y., U.S., P.P., N.D., N.S., N.M1., and N.M3.; formal analysis, B.Y., U.S, N.S., N.M1., N.P., and N.M3; investigation, B.Y., U.S, N.S., N.M1., N.P., and N.M3.; resources, B.Y. and C.C.; data curation, B.Y. and N.M1.; writing—original draft preparation, BY; writing—review and editing, B.Y; visualization, B.Y., U.S., P.P., and N.D.; supervision, B.Y.; project administration, B.Y., U.S., P.P., N.S., and N.P.; funding acquisition, B.Y., U.S., P.P., N.S., and N.P.
Lipidomic Profiling Unveils Sex Differences in Diabetes Risk: Implications for Precision Medicine
Authors: Pina Ana F. , Meneses Maria João , Carli Fabrizia , Patrício Bárbara , Ribeiro Rogério T. , Patarrão Rita S. , Gardete-Correia Luís , Duarte Rui , Boavida José M. , Raposo João F. , Gastaldelli Amalia , Macedo Maria Paula
Published: May 2023

Type 2 diabetes (T2D) is a multifactorial condition whose greatest impact comes from its complications. Not only impaired glucose homeostasis, but also lipid alterations have a relevant role, with insulin derived mechanisms behind this milieu, i.e., glycemia and lipidemia. Thus, we hypothesized that a) distinct glucose and lipid profiles and b) sex differences, particularly in lipids patterns, may be used to identify subjects at higher risk to develop T2D.

The PREVADIAB2 study evaluated metabolic alterations after 5 years in subjects without T2D when participating to PREVADIAB1. Herein, 953 subjects from the PREVADIAB2 cohort were stratified using a hierarchical clustering algorithm, informed by HOMA-IR, IGI,fISR andfIC. The resulting clusters were profiled and the lipidome of a subset (n=488) was assessed by LC/MS-QTOF.

We identified four clusters, named according to their main metabolic features: Liver Sensitive (LS); Pancreas Glucose Sensitive (PGS); Insulin Deficient (ID); and Insulin Resistant (IR). These cluster metabolic patterns were similar between sexes. However, men and women had distinct parameters cut-offs and lipidomic profiles. Overall, women presented higher long chain ceramides. Nonetheless, men had higher ceramide to sphingomyelin ratio and higher lysophosphatidylcholine to phosphatidylcholine ratio. For both genders, the LS cluster had the most advantageous lipid profile, whereas the other clusters presented lipid specificities towards dysmetabolism. This work shows that clustering individuals by distinct insulin-related metabolic features and sex identifies different phenotypes with distinct lipidome profile, thus demonstrating the importance of placing diabetes in a broader context of metabolism beyond glucose.
Rise of escitalopram and the fall of citalopram
Authors: Cavanah Luke R. , Ray Parita , Goldhirsh Jessica L. , Huey Leighton Y. , Piper Brian J.
Published: May 2023

Introduction

Citalopram and escitalopram are among the most used medications and are key treatments for many psychiatric disorders. Previous findings suggest citalopram and escitalopram prescription rates are changing because of the patent for citalopram ending as opposed to evidence of a clear therapeutic advantage, which is called evergreening. This retrospective study focuses on characterizing the chronologic and geographic variation in the use of citalopram and escitalopram among US Medicaid and Medicare patients. We hypothesized that prescription rates of citalopram will decrease with a concurrent increase in escitalopram, consistent with evergreening.

Methods

Citalopram and escitalopram prescription rates and costs per state were obtained from the Medicaid State Drug Utilization Database and Medicare Provider Utilization and Payment Data. Annual prescription rates outside a 95% confidence interval were considered significantly different from the average.

Results

Overall, a decreasing trend for citalopram and an increasing trend for escitalopram prescription rates were noted in both Medicare and Medicaid patients. Cost differences between generic and brand were noted for both drugs, with generic forms being cheaper compared to the brand-name version.

Discussion

Despite limited evidence suggesting that citalopram and escitalopram have any meaningful differences in therapeutic or adverse effects, there exists a noticeable decline in the use of citalopram that cooccurred with an increase in escitalopram prescribing, consistent with our hypothesis. Moreover, among these general pharmacoepidemiologic trends exists significant geographic variability. There was disproportionate spending (relative to their use) on the brand versions of these medicines compared to their generic forms.
Mobilizing faith-based COVID-19 health ambassadors to address COVID-19 health disparities among African American older adults in under-resourced communities: A hybrid, community-based participatory intervention
Authors: Adinkrah Edward K. , Bazargan Shahrzad , Cobb Sharon , Kibe Lucy W. , Vargas Roberto , Waller Joe , Sanchez Humberto , Bazargan Mohsen
Published: May 2023

The COVID-19 pandemic disproportionately affected older adults, particularly those with pre-existing chronic health conditions. To address the health disparity gap and challenges faced by under-resourced African American older adults in South Los Angeles during this period, we implemented a hybrid (virtual/in-person), pre-post, community-based participatory intervention research project utilizing a faith-based lay health advisor model (COVID-19 Health Ambassador Program (CHAP)). We recruited COVID-19 Health Ambassadors (CHAs) and African American older adults (participants) from faith-based organizations who partook in CHA-led meetings and follow-ups that educated and supported the participants. This paper seeks to evaluate this intervention’s implementation using the Consolidated Framework for Implementation Research (CFIR) as a reporting tool with an emphasis on fidelity, challenges, and adaptations based on data collected via stakeholder interviews and surveys. Results: CHAP was delivered to 152 participants by 19 CHAs from 17 faith-based organizations. CHAs assisted with chronic disease management, resolved medication-related challenges, encouraged COVID-19 vaccination, reduced psychological stress and addressed healthcare avoidance behaviors such as COVID-19 vaccine hesitancy among the participants. Challenges encountered include ensuring participant engagement and retention in the virtual format and addressing technological barriers for CHAs and participants. Adaptations made to better suit the needs of participants included providing communication tools and additional training to CHAs to improve their proficiency in using virtual platforms in addition to adapting scientific/educational materials to suit our participants’ diverse cultural and linguistic needs. Conclusion: The community-centered hybrid approach in addition to our partnership with faith-based organizations and their respective COVID-19 health ambassadors proved to be essential in assisting underserved African American older adults manage chronic health conditions and address community-wide health disparities during the COVID-19 pandemic. Adaptability, cultural sensitivity, and teamwork are key to implementing health interventions especially in underserved populations.
Rectal and vaginal challenge with mpox virus increases virus dissemination and contact transmission compared to skin challenge in the multimammate rat (Mastomys natalensis)
Authors: Port Julia R. , Riopelle Jade C. , Smith Samuel G. , Myers Lara , Lewis Matthew C. , Gallogly Shane , Okumura Atsushi , Schulz Jonathan E. , Rosenke Rebecca , Prado-Smith Jessica , Carmody Aaron , Bane Sidy , Smith Brian J. , Saturday Greg , Feldmann Heinz , Rosenke Kyle , Munster Vincent J.
Published: May 2023

The 2022 mpox virus outbreak was sustained by efficient human-to-human transmission and spread predominantly through sexual networks of men who have sex with men (MSM). It is currently unclear what combination of factors resulted in the enhanced transmission. To investigate this, we established the peridomestic African rodentMastomys natalensisas a new rodent model susceptible to infection after intraperitoneal, rectal, vaginal, and transdermal inoculation with an early 2022 human outbreak isolate (Clade IIb). Route-dependent shedding and tissue replication occurred in the presence of self-resolving localized skin, reproductive tract, or rectal lesions. Mucosal inoculation via both the rectal and vaginal route led to increased shedding compared to skin inoculation, and increased replication and a proinflammatory T-cell profile. Contact transmission was higher in rectally inoculated animals. This suggests that the spread in MSM communities may have been enhanced by increased susceptibility of the anal and genital mucosae for infection and subsequent virus release.
Lack of paternal silencing and ecotype-specific expression in head and body lice hybrids
Authors: Marshall Hollie , de la Filia Andrés G. , Cavalieri Ross , Mallon Eamonn B. , Clark John M. , Ross Laura
Published: May 2023

Paternal genome elimination (PGE) is a non-Mendelian inheritance system in which males develop from fertilised eggs but their paternally-inherited chromosomes are eliminated before or during spermatogenesis. Therefore, PGE males only transmit their maternally inherited set of chromosomes to their offspring. PGE has been described in numerous arthropod species, many of which are pests or parasites, posing a severe economic burden on crop production and/or with implications for human health. In order to understand how PGE has evolved on the molecular level, to potentially develop novel control strategies, we need to examine species which display basal forms of PGE. The human louse, Pediculus humanus, represents an ideal model system to understand the molecular underpinnings of PGE. In this study we analysed parent-of-origin allele specific expression patterns in male offspring of crosses between head and body lice ecotypes. We have shown that hybrid adult males of P. humanus display biparental gene expression, which constitutes the first known case of a species with PGE in which genetic activity of paternal chromosomes in the soma is not affected by embryonic heterochromatinization or (partial or complete) elimination. We have also identified maternally-biased genes (potentially imprinted genes) which may be involved in the elimination of paternal chromosomes during spermatogenesis. Finally, we have identified genes which show ecotype-specific expression bias. Given the low genetic diversity between ecotypes this is suggestive for a role of epigenetic processes in ecotype differences. These findings have implications for models of pediculicide resistance in human lice and for the development of novel epigenetic-mediated control strategies.
Immunomodulatory Effects of Atractylodes Lancea in Healthy Volunteers with Dosage Prediction for Cholangiocarcinoma Therapy: a modelling approach
Authors: Sae-heng Teerachat , Karbwang Juntra , Na-Bangchang Kesara
Published: May 2023

Background

A recent study on the immunomodulatory activity ofAtractylodes Lancea(Thunb.) DC. (AL) in healthy Thai subjects revealed that a once daily dose of 1,000 mg AL administered for 21 days significantly inhibited the production of key pro-inflammatory cytokines, while stimulating the production of immune cells. There is however, no reported maximum tolerated dose (MTD) and suggested phase 2A dosage regimens in the literature.

Objective

This study aimed to evaluate the immunomodulatory effectsof Atractylodes Lancea(Thunb.) DC. (AL) in healthy subjects, and to recommend optimal dose regimens for intrahepatic cholangiocarcinoma (iCCA) based on toxicity criteria.

Methods

A physiologically-based pharmacokinetic (PBPK) model, combined with the toxicological approach and the immunomodulatory effect, was used for a dose-finding. The safety and efficacy of each AL regimen were evaluated based on the previous study. At least, a daily OD dose of 1,000 mg AL significantly suppressed the production of all proinflammatory cytokines while significantly increasing the number of peripheral immune cells.

Results

The developed PBPK model well predicted clinical observed data. No significant differences in SII index values were found, but a difference in the lymphocyte-monocyte ratio was found on day 4. The dosage regimens for phase 2A are BID doses of 1,000 or 2,000 mg or OD doses of 2,000 mg. Preliminary results in phase 2A revealed that a once-daily dose of 2,000 mg had a significantly higher median overall survival, progression-free survival, disease control rate, and inhibition of increased tumor size without toxicities compared with a once-daily dose of 1,000 mg and standard supportive care.

Conclusion

A PBPK model, in conjunction with a toxicological approach, could assist in finding the potential dosage regimens for a clinical study, including herbal medicine.
Shear force enhances adhesion ofPseudomonas aeruginosaby counteracting pilus-driven surface departure
Authors: Palalay Jessica-Jae S. , Simsek Ahmet N. , Sabass Benedikt , Sanfilippo Joseph E.
Published: May 2023

Fluid flow is thought to prevent bacterial adhesion, but some bacteria use adhesins with catch bond properties to enhance adhesion under high shear forces. However, many studies on bacterial adhesion either neglect the influence of shear force or use shear forces that are not typically found in natural systems. In this study, we use microfluidics and single-cell imaging to examine how the human pathogenPseudomonas aeruginosainteracts with surfaces when exposed to shear forces typically found in the human body (0.1 pN to 10 pN). Through cell tracking, we demonstrate that the angle between the cell and the surface predicts if a cell will depart the surface. We discover that at lower shear forces, type IV pilus retraction tilts cells away from the surface, promoting surface departure. Conversely, we show that higher shear forces counterintuitively enhance adhesion by counteracting type IV pilus retraction-dependent cell tilting. Thus, our results reveal thatP. aeruginosaexhibits behavior reminiscent of a catch bond, without having a specific adhesin that is enhanced by force. Instead,P. aeruginosacouples type IV pilus dynamics and cell geometry to tune adhesion to its mechanical environment, which likely provides a benefit in dynamic host environments.
A Cryo-to-Liquid Phase Correlative Light Electron Microscopy Workflow for the Visualization of Biological Processes in Graphene Liquid Cells
Authors: Rutten Luco , Joosten Ben , Schaart Judith , de Beer Marit , Roverts Rona , Gräber Steffen , Jahnen-Dechent Willi , Akiva Anat , Macías-Sánchez Elena , Sommerdijk Nico
Published: May 2023

Liquid phase electron microscopy (LP-EM) has emerged as a powerful technique forin-situobservation of material formation in liquid. However, monitoring these processes requires the repeated interaction of the electron beam with the aqueous environment leading to the decomposition of water molecules (radiolysis), which affects the formation processes under investigation. Graphene’s ultra-conductive properties have made it an efficient way to mitigate this problem, as it acts as an electron scavenger when used as a window material. Using the strategy, the process of interest is initiated when the graphene liquid cells (GLCs) are sealed. This means that the process cannot be imaged at early time points since microscope preparation and initiation of image acquisition at the region of interest are time-consuming.

Here we report a novel cryogenic/liquid phase correlative light/electron microscopy workflow that addresses the most significant limitations of the graphene liquid cells, while combining the advantages of fluorescence and electron microscopy. This workflow allows imaging to be initiated at a predetermined space and time by vitrifying and thawing at a selected time point. We demonstrate the workflow first by observing multiple day crystallization processes and highlight its potential by observing a biological process: the complexation of calciprotein particles. With this observation, we show the exciting possibilities for LP-EM in biology.
Site-Specific Introduction of Alanines for the NMR Investigation of Low-Complexity Regions and Large Biomolecular Assemblies
Authors: Elena-Real Carlos A. , Urbanek Annika , Imbert Lionel , Morató Anna , Fournet Aurélie , Allemand Frédéric , Sibille Nathalie , Boisbouvier Jerome , Bernadó Pau
Published: May 2023

NMR studies of large biomolecular machines and highly repetitive proteins remain challenging due to the difficulty of assigning signals to individual nuclei. Here, we present an efficient strategy to address this challenge by engineering aPyrococcus horikoshiitRNA/alanyl-tRNA synthetase pair that enables the incorporation of up to three isotopically labeled alanine residues in a site-specific manner usingin vitroprotein expression. We have demonstrated the general applicability of this approach for NMR assignment by introducing isotopically labeled alanines into four proteins, including the 300-kDa molecular chaperone ClpP and the alanine-rich Phox2B transcription factor. For large protein assemblies, our labeling approach enables unambiguous assignments, while avoiding potential artefacts induced by site-specific mutations. When applied to Phox2B, which contains two poly-alanine tracts of nine and twenty alanines, we observe that the helical stability is strongly dependent on the homorepeat length, demonstrating structural cooperativity. The capacity to selectively introduce alanines with distinct labeling patterns is a powerful tool to probe structure and dynamics of biomolecular systems that are out of the reach of traditional structural biology methods.
O antigen biogenesis sensitisesEscherichia coliK-12 to bile salts, a likely cause for how it lost its O antigen
Authors: Qin Jilong , Hong Yaoqin , Morona Renato , Totsika Makrina
Published: May 2023

Escherichia coliK-12 is a model organism for bacteriology and has served as a workhorse for molecular biology and biochemistry for over a century since its first isolation in 1922. However,Escherichia coliK-12 strains are phenotypically devoid of an O antigen (OAg) since early reports in the scientific literature. Recent studies reported the presence of independent mutations that abolish OAg biogenesis inE. coliK-12 strains from the same original source, suggesting unknown evolutionary forces have selected for loss of OAg during the early propagation of K-12. Here, we show for the first time that restoration of OAg inE. coliK-12 strain MG1655 synergistically sensitises bacteria to vancomycin with bile salts (VBS). Suppressor mutants surviving lethal doses of VBS mostly contained disruptions in OAg biogenesis. We present data supporting a model where the transient presence and accumulation of lipid-carried OAg intermediates in the bacterial periplasm interfere with peptidoglycan synthesis, causing growth defects that are synergistically enhanced by bile salts. Lastly, we demonstrate that continuous bile salt exposure of OAg-producing MG1655 in the laboratory, can recreate a scenario where OAg disruption is selected for. Hence our work provides a likely explanation for the long-held mystery of howE. coliK-12 lost its OAg production and opens new avenues for exploring long-standing questions on the intricate network coordinating the synthesis of different cell envelope components in Gram-negative bacteria.

Significance statement

Escherichia coliK-12 is the most studied microorganism, widely used in laboratories for studying bacteriology and as a tool for molecular biology. The reason why it is devoid of O antigen remains a long-standing question. Our work has uncovered a previously unknown selection pressure of bile salts on bacterial O antigen biogenesis, which provides a plausible scenario for how the early propagation ofE. coliK-12 strains in bile salt containing media could have led to loss of O antigen in K-12. Our results also suggest that the accumulation of O antigen intermediates in the bacterial periplasm may interfere with bacterial cell wall synthesis, which paves a new research direction into the interplay of different cell envelope component synthesis pathways.