bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship Between Time Spent on Social Media and Adolescent Cigarette, E-cigarette, and Dual Use: A Longitudinal Analysis of the UK Millennium Cohort Study
Authors: Purba Amrit Kaur , Henderson Marion , Baxter Andrew , Pearce Anna , Katikireddi S Vittal
Published: April 2024

Introduction

To estimate the effect of social media use in 14 year olds on risk of and inequalities in cigarette, e-cigarette, and dual use at 17 years, using the UK-representative Millennium Cohort Study (born 2000–2002).

Aims and Methods

The relationship of time spent on social media (using questionnaires [n = 8987] and time-use-diaries [n = 2520]) with cigarette, e-cigarette, and dual use was estimated using adjusted odds ratios (AORs) or relative risk ratios (ARRRs). Effect modification was examined (using parental education as an indicator for socioeconomic circumstances) by comparing adjusted risk differences within low and high-parental education groups. Analyses accounted for prespecified confounders (identified via directed acyclic graphs), baseline outcome measures (to address reverse causality), sample design, attrition, and item-missingness (through multiple imputation).

Results

Time spent on social media was associated with increased risk of cigarette, e-cigarette, and dual use in a dose–response manner. Social media use for ≥2 hours/day (vs. 1–<30 minutes) was associated with increased cigarette (AOR 2.76 [95% confidence interval 2.19 to 3.48]), e-cigarette (3.24 [2.59 to 4.05]), and dual use (ARRR 4.11 [2.77 to 6.08]). The risk of cigarette use among 30 minutes–<1 hour/day users (vs. non-users) were smaller in those with high versus low parental education (ARDs 1.4% vs. 12.4%). Similar findings were observed across the higher time categories. Analyses using time-use-diaries, in complete case samples, and with additional adjustment for baseline outcome measures generally revealed similar findings.

Conclusions

After accounting for observed confounders and potential reverse causality, findings suggest social media use increases the risk of cigarette, e-cigarette, and dual use in a dose–response manner. Guidance addressing adolescent online safety should be prioritized.

Implications

This study’s identification of a dose–response relationship and differential effects across socioeconomic groups, could assist in the development of guidance on time spent on social media. The adverse effects of social media use on adolescent cigarette, e-cigarette, and dual use supports legislation aimed at promoting adolescent online safety. Study findings strengthen calls to prohibit social media marketing of nicotine-related products and importantly highlight the need to increase awareness and understanding of the underlying algorithms which drive adolescent exposure to nicotine-related content on social media to ensure they are functioning in a way that best serves the adolescent population.
Naringenin restricts the colonization and growth of Ralstonia solanacearum in tobacco mutant KCB-1
Authors: Shi Haoqi , Jiang Jiale , Yu Wen , Cheng Yazhi , Wu Shengxin , Zong Hao , Wang Xiaoqiang , Ding Anming , Wang Weifeng , Sun Yuhe
Published: April 2024

Bacterial wilt severely jeopardizes plant growth and causes enormous economic loss in the production of many crops, including tobacco (Nicotiana tabacum). Here, we first demonstrated that the roots of bacterial wilt-resistant tobacco mutant KCB-1 can limit the growth and reproduction of Ralstonia solanacearum. Secondly, we demonstrated that KCB-1 specifically induced an upregulation of naringenin content in root metabolites and root secretions. Further experiments showed that naringenin can disrupt the structure of R. solanacearum, inhibit the growth and reproduction of R. solanacearum, and exert a controlling effect on bacterial wilt. Exogenous naringenin application activated the resistance response in tobacco by inducing the burst of reactive oxygen species and salicylic acid deposition, leading to transcriptional reprogramming in tobacco roots. Additionally, both external application of naringenin in CB-1 and overexpression of the Nicotiana tabacum chalcone isomerase (NtCHI) gene, which regulates naringenin biosynthesis, in CB-1 resulted in a higher complexity of their inter-root bacterial communities than in untreated CB-1. Further analysis showed that naringenin could be used as a marker for resistant tobacco. The present study provides a reference for analyzing the resistance mechanism of bacterial wilt-resistant tobacco and controlling tobacco bacterial wilt.
LIKE EARLY STARVATION 1 interacts with amylopectin during starch biosynthesis
Authors: Osman Rayan , Bossu Mélanie , Dauvillée David , Spriet Corentin , Liu Chun , Zeeman Samuel C , D’Hulst Christophe , Bompard Coralie
Published: April 2024

Starch is the major energy storage compound in plants. Both transient starch and long-lasting storage starch accumulate in the form of insoluble, partly crystalline granules. The structure of these granules is related to the structure of the branched polymer amylopectin: linear chains of glucose units organized in double helices that align to form semicrystalline lamellae, with branching points located in amorphous regions between them. EARLY STARVATION 1 (ESV1) and LIKE EARLY STARVATION 1 (LESV) proteins are involved in the maintenance of starch granule structure and in the phase transition of amylopectin, respectively, in Arabidopsis (Arabidopsis thaliana). These proteins contain a conserved tryptophan-rich C-terminal domain folded into an antiparallel β-sheet, likely responsible for binding of the proteins to starch, and different N-terminal domains whose structure and function are unknown. In this work, we combined biochemical and biophysical approaches to analyze the structures of LESV and ESV1 and their interactions with the different starch polyglucans. We determined that both proteins interact with amylopectin but not with amylose and that only LESV is capable of interacting with amylopectin during starch biosynthesis. While the C-terminal domain interacts with amylopectin in its semicrystalline form, the N-terminal domain of LESV undergoes induced conformational changes that are probably involved in its specific function of mediating glucan phase transition. These results clarify the specific mechanism of action of these 2 proteins in the biosynthesis of starch granules.
Comparison of transcriptomic profiles between HFPO-DA and prototypical PPARα, PPARγ, and cytotoxic agents in mouse, rat, and pooled human hepatocytes
Authors: Heintz Melissa M , Klaren William D , East Alexander W , Haws Laurie C , McGreal Steven R , Campbell Rebecca R , Thompson Chad M
Published: April 2024

Like many per- or polyfluorinated alkyl substances (PFAS), toxicity studies with HFPO-DA (ammonium, 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate), a short-chain PFAS used in the manufacture of some types of fluorinated polymers, indicate that the liver is the primary target of toxicity in rodents following oral exposure. Although the current weight of evidence supports the PPARα mode of action (MOA) for liver effects in HFPO-DA-exposed mice, alternate MOAs have also been hypothesized including PPARγ or cytotoxicity. To further evaluate the MOA for HFPO-DA in rodent liver, transcriptomic analyses were conducted on samples from primary mouse, rat, and pooled human hepatocytes treated for 12, 24, or 72 h with various concentrations of HFPO-DA, or agonists of PPARα (GW7647), PPARγ (rosiglitazone), or cytotoxic agents (ie, acetaminophen or d-galactosamine). Concordance analyses of enriched pathways across chemicals within each species demonstrated the greatest concordance between HFPO-DA and PPARα agonist GW7647-treated hepatocytes compared with the other chemicals evaluated. These findings were supported by benchmark concentration modeling and predicted upstream regulator results. In addition, transcriptomic analyses across species demonstrated a greater transcriptomic response in rodent hepatocytes treated with HFPO-DA or agonists of PPARα or PPARγ, indicating rodent hepatocytes are more sensitive to HFPO-DA or PPARα/γ agonist treatment. These results are consistent with previously published transcriptomic analyses and further support that liver effects in HFPO-DA-exposed rodents are mediated through rodent-specific PPARα signaling mechanisms as part of the MOA for PPARα activator-induced rodent hepatocarcinogenesis. Thus, effects observed in mouse liver are not appropriate endpoints for toxicity value development for HFPO-DA in human health risk assessment.
Chronic pain in pediatric patients: epidemiology, pathophysiology, and mitigation strategies
Authors: Rodriguez-Restrepo Andrea , AuBuchon Jacob D.
Published: April 2024

Purpose of review

To provide an updated summary on the epidemiology, pathophysiology, and treatment strategies of chronic pain in pediatric patients and its differences with chronic pain in adults.

Recent findings

Chronic pain in children is common, can be debilitating and can progress into adulthood, thus it requires an interdisciplinary evaluation and management. Targeting interdisciplinary care, including psychology, physical, and/or occupational therapy, has been shown to improve pain and function. Recent decline in mental health post pandemic has correlated with increase in pediatric chronic pain thus the need to identify patients at risk and offer early interdisciplinary treatment.

Chronic pediatric pain should be addressed under the biopsychosocial model, where the biological, psychological, and social factors are evaluated on how they influence the pain perception, pain experience, functional ability, and treatment focus. Pain education to patients and their families is the crucial initial step towards a functional rehabilitation of pain.
Obesity and anesthesia
Authors: Arora Lovkesh , Sharma Surangama , Carillo James F.
Published: April 2024

Purpose of review

Surgical procedures on obese patients are dramatically increasing worldwide over the past few years. In this review, we discuss the physiopathology of predominantly respiratory system in obese patients, the importance of preoperative evaluation, preoxygenation and intraoperative positive end expiratory pressure (PEEP) titration to prevent pulmonary complications and the optimization of airway management and oxygenation to reduce or prevent postoperative respiratory complications.

Recent findings

Many patients are coming to preoperative clinic with medication history of glucagon-like-peptide 1 agonists (GLP-1) agonists and it has raised many questions regarding Nil Per Os (NPO)/perioperative fasting guidelines due to delayed gastric emptying caused by these medications. American Society of Anesthesiologists (ASA) has come up with guiding document to help with such situations. Ambulatory surgery centers are doing more obesity cases in a safe manner which were deemed unsafe at one point. Quantitative train of four (TOF) monitoring, better neuromuscular reversal agents and gastric ultrasounds seemed to have made a significant impact in the care of obese patients in the perioperative period.

Obese patients are at higher risk of perioperative complications, mainly associated with those related to the respiratory function. An appropriate preoperative evaluation, intraoperative management, and postoperative support and monitoring is essential to improve outcome and increase the safety of the surgical procedure.
Patient Location and Disparities in Access to Fertility Preservation for Women With Gynecologic or Breast Cancer
Authors: Kanbergs Alexa , Jorgensen Kirsten , Agusti Nuria , Viveros-Carreño David , Wu Chi-Fang , Nitecki Roni , Harris John A. , Woodard Terri , Ramphul Ryan , Rauh-Hain Jose Alejandro
Published: April 2024

OBJECTIVE:

To assess the effect of geographic factors on fertility-sparing treatment or assisted reproductive technology (ART) utilization among women with gynecologic or breast cancers.

METHODS:

We conducted a cohort study of reproductive-aged patients (18–45 years) with early-stage cervical, endometrial, or ovarian cancer or stage I–III breast cancer diagnosed between January 2000 and December 2015 using linked data from the California Cancer Registry, the California Office of Statewide Health Planning and Development, and the Society for Assisted Reproductive Technology. Generalized linear mixed models were used to evaluate associations between distance from fertility and gynecologic oncology clinics, as well as California Healthy Places Index score (a Census-level composite community health score), and ART or fertility-sparing treatment receipt.

RESULTS:

We identified 7,612 women with gynecologic cancer and 35,992 women with breast cancer. Among all patients, 257 (0.6%) underwent ART. Among patients with gynecologic cancer, 1,676 (22.0%) underwent fertility-sparing treatment. Stratified by quartiles, residents who lived at increasing distances from gynecologic oncology or fertility clinics had decreased odds of undergoing fertility-sparing treatment (gynecologic oncology clinics: Q2, odds ratio [OR] 0.76, 95% CI, 0.63–0.93, P=.007; Q4, OR 0.72, 95% CI, 0.56–0.94, P=.016) (fertility clinics: Q3, OR 0.79, 95% CI, 0.65–0.97, P=.025; Q4, OR 0.67, 95% CI, 0.52–0.88, P=.004), whereas this relationship was not observed among women who resided within other quartiles (gynecologic oncology clinics: Q3, OR 0.81 95% CI, 0.65–1.01, P=.07; fertility clinics: Q2, OR 0.87 95% CI, 0.73–1.05, P=.15). Individuals who lived in communities with the highest (51st–100th percentile) California Healthy Places Index scores had greater odds of undergoing fertility-sparing treatment (OR 1.29, 95% CI, 1.06–1.57, P=.01; OR 1.66, 95% CI, 1.35–2.04, P=.001, respectively). The relationship between California Healthy Places Index scores and ART was even more pronounced (Q2 OR 1.9, 95% CI, 0.99–3.64, P=.05; Q3 OR 2.86, 95% CI, 1.54–5.33, P<.001; Q4 OR 3.41, 95% CI, 1.83–6.35, P<.001).

CONCLUSION:

Geographic disparities affect fertility-sparing treatment and ART rates among women with gynecologic or breast cancer. By acknowledging geographic factors, health care systems can ensure equitable access to fertility-preservation services.
High-Dose Buprenorphine Initiation in the Management of Opioid Use Disorder in Pregnancy
Authors: Berry Marissa , Kiefer Miranda K. , Hinely Katherine A. , Bowden Heather , Jordan Audra , Vilensky Michael , Rood Kara M.
Published: April 2024

Buprenorphine is commonly used as a treatment for opioid use disorder (OUD). Transition to buprenorphine traditionally has been done using a low-dose initiation regimen due to concerns surrounding precipitated withdrawal. There are increasing data supporting use of a high-dose initiation regimen in the nonpregnant population. This retrospective case series describes six individuals with OUD who underwent high-dose buprenorphine initiation in pregnancy. There were no instances of sedation, respiratory depression, supplemental oxygen use, or death. All individuals were successfully transitioned to buprenorphine. These findings provide support for high-dose buprenorphine initiation in pregnancy, but future large studies are needed.
Lymphangitic Melanomatosis: Case Report of Intralymphatic Spread of Melanoma in a 66-year-old Man
Authors: Srivatsa Shantanu , Smith Collin-Jamal , Sangüeza Omar P. , Miedema Jayson , Collichio Frances A. , Googe Paul B.
Published: April 2024

Melanoma with lymphatic invasion has been associated with increased risk of metastasis, but the mechanisms and clinical implications are poorly understood. Although current reports have documented angiotropic spread of melanoma and suggest lymphatic spread of melanoma to increase the likelihood of metastasis, to our knowledge, lymphangitic metastatic melanoma resembling cutaneous carcinomatosis or presenting with facial hyperpigmentation has not been described. In this case report, we describe extensive cutaneous intralymphatic spread of melanoma, or lymphangitic melanomatosis, producing macular skin pigmentation in a 66-year-old man.
Frozen Section Histoanatomy of the Peritarsal Eyelid
Authors: Zhang Junqian , Lee Vivian , Elenitsas Rosalie , McMurray Stacy L. , Sobanko Joseph F. , Briceño César A. , Mehta Sonul , Miller Christopher J.
Published: April 2024

BACKGROUND

Mohs surgery of eyelid skin cancers requires detailed knowledge of anatomy for precise surgery and accurate evaluation of histology.

OBJECTIVE

To review the histology of the peritarsal eyelid using frozen sections as encountered intraoperatively by Mohs surgeons.

METHODS

The authors review the literature describing the anatomy and histology of the peritarsal eyelid from the lens of a Mohs surgeon. Histology from select Mohs cases is used to frame the discussion of the microanatomy of this region.

RESULTS

The peritarsal eyelids contain a unique mixture of skin, muscle, tarsus, glandular tissue, and conjunctiva. The histologic appearance of many of these structures differs from skin found outside of this anatomic region. Tumors of the eyelid and periocular region may mimic normal histologic structures found within the peritarsal eyelid.

CONCLUSION

The peritarsal eyelids have unique anatomy and associated histologic structures. Knowledge of the detailed histoanatomy is required for confident execution of Mohs surgery in this anatomic region.
Glutathione S-Transferase α4 Alleviates Hyperlipidemia-Induced Vascular Neointimal Hyperplasia in Arteriovenous Grafts via Inhibiting Endoplasmic Reticulum Stress
Authors: Zhou Chenchen , Zhong Yanxia , Chu Yun , Chen Renyu , Wang Yurou , Zheng Yingfang , Dai Hongkai , Zhan Chengye , Xie Aini , Luo Jinlong
Published: April 2024

Neointimal hyperplasia causes the failure of coronary artery bypass grafting. Our previous studies have found that endothelial dysfunction is 1 candidate for triggering neointimal hyperplasia, but which factors are involved in this process is unclear. Glutathione S-transferase α4 (GSTA4) plays an important role in metabolizing 4-hydroxynonenal (4-HNE), a highly reactive lipid peroxidation product, which causes endothelial dysfunction or death. Here, we investigated the role of GSTA4 in neointima formation after arteriovenous grafts (AVGs) with or without high-fat diet (HFD). Compared with normal diet, HFD caused endothelial dysfunction and increased neointima formation, concomitantly accompanied by downregulated expression of GSTA4 at the mRNA and protein levels. In vitro, overexpression of GSTA4 attenuated 4-HNE–induced endothelial dysfunction and knockdown of GSTA4 aggravated endothelial dysfunction. Furthermore, silencing GSTA4 expression facilitated the activation of 4-HNE–induced endoplasmic reticulum stress and inhibition of endoplasmic reticulum stress pathway alleviated 4-HNE–induced endothelial dysfunction. In addition, compared with wild-type mice, mice with knockout of endothelial-specific GSTA4 (GSTA4 endothelial cell KO) exhibited exacerbated vascular endothelial dysfunction and increased neointima formation caused by HFD. Together, these results demonstrate the critical role of GSTA4 in protecting the function of endothelial cells and in alleviating hyperlipidemia-induced vascular neointimal hyperplasia in arteriovenous grafts.
Effects of Pterostilbene on Heart and Lung Oxidative Stress Parameters in 2 Experimental Models of Cardiovascular Disease: Myocardial Infarction and Pulmonary Arterial Hypertension
Authors: de Castro Alexandre Luz , Duarte Ortiz Vanessa , Hickmann Alexandre R. , Santos Lacerda Denise , Türck Patrick , Campos Carraro Cristina , Freitas Schauana , Bello Klein Adriane , Bassani Valquiria , da Rosa Araujo Alex Sander
Published: April 2024

Myocardial infarction (MI) and pulmonary arterial hypertension (PAH) are 2 prevalent cardiovascular diseases. In both conditions, oxidative stress is associated with a worse prognosis. Pterostilbene (PTE), an antioxidant compound, has been studied as a possible therapy for cardiovascular diseases. This study aims to evaluate the effect of PTE on oxidative stress in the hearts of animals with MI and in the lungs of animals with PAH. Male Wistar rats were used in both models. In the MI model, the experimental groups were sham, MI, and MI + PTE. In the PAH model, the experimental groups were control, PAH, and PAH + PTE. Animals were exposed to MI through surgical ligation of the left coronary artery, or to PAH, by the administration of monocrotaline (60 mg/kg). Seven days after undergoing cardiac injury, the MI + PTE animals were treated with PTE (100 mg/kg day) for 8 days. After this, the heart was collected for molecular analysis. The PAH + PTE animals were treated with PTE (100 mg/kg day) for 14 days, beginning 7 days after PAH induction. After this, the lungs were collected for biochemical evaluation. We found that PTE administration attenuated the decrease in ejection fraction and improved left ventricle end-systolic volume in infarcted animals. In the PAH model, PTE improved pulmonary artery flow and decreased reactive oxygen species levels in the lung. PTE administration promoted protective effects in terms of oxidative stress in 2 experimental models of cardiac diseases: MI and PAH. PTE also improved cardiac function in infarcted rats and pulmonary artery flow in animals with PAH.
Nurses and Nursing Students With Substance Use Disorders
Authors: Molloy Patricia A.
Published: April 2024

Substance use disorder (SUD) is a significant problem for millions of Americans. The incidence of SUDs among nurses and nursing students is thought to be like that found in the general population. Some studies suggest increases in substance use among college students given stressors related to the COVID-19 pandemic. Nurses are in unique positions to care for one another as we care for our patients. Identification, referral, and treatment of SUDs can prevent both nurses and nursing students from terminating their careers or nursing programs of study. The purposes of this article were to increase nurses' knowledge of SUDs among nurses and nursing students, provide an organizing framework for identification of substance problems among nurses/nursing students, and discuss ways to create a culture of support and recovery for nurses/nursing students with SUDs.
Damage-Associated Molecular Patterns as Mediators of Thrombus Formation on Dialyzer Membrane in Critically Ill Patients
Authors: Okamoto Kaori , Ito Takashi , Sato Sara , Yamamoto Masahiro , Takahashi Masaki , Takahashi Yuki , Tsuchida Takumi , Mizugaki Asumi , Hayakawa Mineji
Published: April 2024

This prospective study investigated the relationship between inflammation, damage-associated molecular patterns (DAMPs), and thrombus formation on dialyzer membranes in critically ill patients undergoing renal replacement therapy (RRT) from July 2020 to August 2022, identifying mechanisms and interventions to prevent clotting. The patients were divided into two groups: inflammatory (n = 56, serum C-reactive protein >10 mg/dl) and noninflammatory control (n = 45, serum C-reactive protein <5 mg/dl). Cell-free deoxyribonucleic acid (DNA) levels, high mobility group box 1 protein (HMGB1), histone H3, and myeloperoxidase (MPO) in the lumen of the hollow fiber membrane of the dialyzer were quantified. Immunostaining assessed leukocytes, fibrin fibers, and platelet thrombi on the luminal surface of the hollow fiber membrane. The inflammatory group, compared to controls, exhibited elevated cell-free DNA, HMGB1, and MPO levels, although histone H3 remained unchanged. Damage-associated molecular patterns increased with disseminated intravascular coagulation (DIC) severity. Immunostaining in the inflammatory group revealed leukocytes, amorphous nuclei, neutrophil extracellular trap-like structures, fibrin fibers, and platelet thrombi on the hollow fiber membrane’s luminal surface. Elevated DAMP levels in severely inflamed patients’ dialyzer membranes, correlating with DIC severity, indicate a link between inflammation, coagulation activation, and dialyzer clotting. Research into thrombus prevention in RRT for DIC-affected critically ill patients is warranted.
Phosphate sensing in health and disease
Authors: Zechner Christoph , Rhee Eugene P.
Published: April 2024

Purpose of review

Disruptions of phosphate homeostasis are associated with a multitude of diseases with insufficient treatments. Our knowledge regarding the mechanisms underlying metazoan phosphate homeostasis and sensing is limited. Here, we highlight four major advancements in this field during the last 12–18 months.

Recent findings

First, kidney glycolysis senses filtered phosphate, which results in the release of glycerol 3-phosphate (G-3-P). Circulating G-3-P then stimulates synthesis of the phosphaturic hormone fibroblast growth factor 23 in bone. Second, the liver serves as a postprandial phosphate reservoir to limit serum phosphate excursions. It senses phosphate ingestion and triggers renal excretion of excess phosphate through a nerve-dependent mechanism. Third, phosphate-starvation in cells massively induces the phosphate transporters SLC20A1/PiT1 and SLC20A2/PiT2, implying direct involvement of cellular phosphate sensing. Under basal phosphate-replete conditions, PiT1 is produced but immediately destroyed, which suggests a novel mechanism for the regulation of PiT1 abundance. Fourth, Drosophila melanogaster intestinal cells contain novel organelles called PXo bodies that limit intracellular phosphate excursions. Phosphate starvation leads to PXo body dissolution, which triggers midgut proliferation.

These studies have opened novel avenues to dissect the mechanisms that govern metazoan phosphate sensing and homeostasis with the potential to identify urgently needed therapeutic targets.
New therapeutic perspectives for vascular and valvular calcifications in chronic kidney disease
Authors: Huish Sharon , Sinha Smeeta
Published: April 2024

Purpose of review

Vascular and valvular calcification are associated with cardiovascular morbidity and mortality in people with chronic kidney disease (CKD). Uncertainty exists regarding therapeutic strategies to attenuate calcification. This review outlines the pathophysiological mechanisms contributing to vascular and valvular calcification, considers the mechanisms of action of therapeutic interventions, and reports the latest outcomes from interventional studies.

Recent findings

Conventional therapies targeted at CKD-mineral and bone disorder (MBD) modulation have yielded conflicting or inconclusive results. Magnesium and vitamin K supplementation appear to offer attenuation of coronary artery calcification but inconsistent findings justify the need for further studies. Strategies targeting hydroxyapatite formation such as sodium thiosulphate and hexasodium fytate show promise and are worthy of further evaluation. The serum calcification propensity assay (T50) correlates with severity and progression; it holds promise as a potential future clinical tool for screening monitoring calcification risk.

Whilst knowledge of the pathophysiology of vascular calcification has grown and therapeutic approaches appear promising, as yet no medication has been approved to treat vascular or valvular calcification, or calciphylaxis.
Aneurinibacillus uraniidurans sp. nov., a uranium-resistant bacterium isolated from uranium-contaminated soil
Authors: Zhang Lijuan , Wang Ning , Huang Wei , Luo Yi , Wu Longyuan , Song Bo , Zheng Guofeng , Liu Zaidao , Zhang Yongwen , Wang Suling , Wang Wei , Sheng Jiandong
Published: April 2024

A novel Gram-positive strain, B1T, was isolated from uranium-contaminated soil. The strain was aerobic, rod-shaped, spore-forming, and motile. The strain was able to grow at 20−45 °C, at pH 6.0–9.0, and in the presence of 0–3 % (w/v) NaCl. The complete genome size of the novel strain was 3 853 322 bp. The genomic DNA G+C content was 45.5 mol%. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain B1T has the highest similarity to Aneurinibacillus soli CB4T (96. 71 %). However, the novel strain showed an average nucleotide identity value of 89.02 % and a digital DNA–DNA hybridization value of 37.40 % with strain CB4T based on the genome sequences. The major fatty acids were iso-C15 : 0 and C16 : 0. The predominate respiratory quinone was MK7. Diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, phosphatidylglycerol, unidentified phospholipids, an unidentified aminolipid and an unidentified lipid were identified as the major polar lipids. The phylogenetic, phenotypic, and chemotaxonomic analyses showed that strain B1T represents a novel species of the genus Aneurinibacillus, for which the name Aneurinibacillus uraniidurans sp. nov. is proposed. The type strain is B1T (=GDMCC 1.4080T=JCM 36228T). Experiments have shown that strain B1T demonstrates uranium tolerance.
Acceptability, feasibility and appropriateness of intensified health education, SMS/phone tracing and transport reimbursement for uptake of voluntary medical male circumcision in a sexually transmitted infections clinic in Malawi: a mixed methods study
Authors: Matoga Mitch M. , Kudowa Evaristar , Chikuni Joachim , Tsidya Mercy , Tseka Jennifer , Ndalama Beatrice , Bonongwe Naomi , Mathiya Esther , Jere Edward , Yatina Dumbo , Kamtambe Blessings , Kapito Martin , Hosseinipour Mina C. , Chasela Charles S. , Jewett Sara
Published: April 2024

Introduction

Uptake of voluntary medical male circumcision (VMMC) remains a challenge in many settings. Innovative implementation strategies are required to scale-up VMMC uptake.

Methodology

RITe was a multi-faceted intervention comprising transport reimbursement (R), intensified health education (IHE) and SMS/Telephone tracing (Te), which increased the uptake of VMMC among uncircumcised men with sexually transmitted infections (STIs) in Malawi. Using a concurrent exploratory mixed-method approach, we assessed the intervention’s acceptability, feasibility and appropriateness among men with STIs and healthcare workers (HCWs) at Bwaila District Hospital. Participants completed Likert scale surveys and participated in-depth interviews (IDIs) and focus group discussions (FGDs). We calculated percentages of responses to survey items and summarized common themes using thematic analysis. Median scores and interquartile ranges (IQR) were calculated for acceptability, feasibility and appropriateness of each strategy at baseline and end-line and compared using the Wilcoxon signed rank test.

Results

A total of 300 surveys, 17 IDIs and 4 FGDs were conducted with men and HCWs between baseline and end-line. The mean age for men in the survey was 29 years (SD ±8) and most were married/cohabiting (59.3%). Mean age for HCWs was 38.5 years (SD ±7), and most were female (59.1%). For acceptability, participants agreed that RITe was welcome, approvable, and likable. Despite participants agreeing that RITe was a good idea, culture and religion influenced appropriateness, particularly at baseline, which improved at end-line for Te and R. For feasibility, HCWs agreed that RITe was easy to implement, but expressed concerns that R (end-line median = 4, IQR: 2, 4) and Te (end-line median = 4, IQR: 4, 4), were resource intensive, hence unsustainable. Interviews corroborated the survey results. Participants reported that IHE provided important information, Te was a good reminder and R was attractive, but they reported barriers to R and Te such as electricity, limited access to phones and distrust in the government.

Conclusions

The RITe intervention was acceptable, feasible and appropriate. However, culture/religion and structural barriers affected perceptions of appropriateness and feasibility, respectively. Continued awareness raising on VMMC and addressing setting-specific structural factors are required to overcome barriers that impede demand-creation interventions for VMMC.

Study registration

ClinicalTrials.govidentifier:NCT04677374. Registered on December 18, 2020.
Cardiovascular events associated with CDK4/6 inhibitors based on randomized controlled trials or cohort trials: a safety meta-analysis
Authors: Zhang Chengrong , Shen Guoshuang , Li Shengmei , Ma Fei , Li Huihui , Tang Yuyao , Li YongXin , Li Zhoujuan , Zhu Zijun , Qiu Tianlei , Liu Zhilin , Zhao Yi , Huang Shifeng , Zhao Fuxing , Kong Fanzhen , Zhao Jiuda
Published: April 2024

Background

CDK4/6 inhibitors is highly valued, but the incidence of cardiovascular events (CVAEs) associated with CDK4/6 inhibitors is not clear.

Methods

Eligible CVAEs were extracted from theClinicalTrials.govregistry. A systematic search of electronic databases (PubMed, Embase, Cochrane Library, and important meetings) until 3 September 2023 was conducted. A disproportionality analysis was performed from the first quarter (Q1) of 2013 to Q1 of 2023 using data from the FDA Adverse Event Reporting System database. Study heterogeneitywas assessed using theI2statistic. Using Peto OR and inverse variance methods to calculate the risk and incidence of CVAEs associated with CDK4/6 inhibitors.

Findings

21 RCTs and cohort trials (n=24,331) were included. During the follow-up period of 8.4 to 34.0 months, CDK4/6 inhibitors significantly increased the risk of CVAEs (Peto OR, 1.64, 95% confidence interval, 1.23 - 2.21,P< 0.01). The rates of QT prolongation and deep vein thrombosis were 98.83 (89.6-100.1) and 6.41 (5.23-7.18) per 1000 patients, respectively. Moreover, we identified 11 CVAEs that were not reported in RCTs or cohort studies, acute coronary syndrome, atrial fibrillation, and mobile thrombophlebitis etc. were strongly correlated with CDK4/6 inhibitors. Furthermore, the risk of CVAEs varied depending on the specific CDK4/6 inhibitors used, its combination with different endocrine therapies, and the patient’s treatment stage.

Interpretation

CDK4/6 inhibitors increase the risk of CVAEs, some of which may lead to serious consequences, early recognition and management of CVAEs is of great importance in clinical practice.
Breast imaging with an ultra-low field MRI scanner: a pilot study
Authors: Shen Sheng , Koonjoo Neha , Longarino Friderike K. , Lamb Leslie R. , Villa Camacho Juan C. , Hornung Torben P.P. , Ogier Stephen E. , Yan Susu , Bortfeld Thomas R. , Saksena Mansi A. , Keenan Kathryn E. , Rosen Matthew S.
Published: April 2024

Breast cancer screening is necessary to reduce mortality due to undetected breast cancer. Current methods have limitations, and as a result many women forego regular screening. Magnetic resonance imaging (MRI) can overcome most of these limitations, but access to conventional MRI is not widely available for routine annual screening. Here, we used an MRI scanner operating at ultra-low field (ULF) to image the left breasts of 11 women (mean age, 35 years ±13 years) in the prone position. Three breast radiologists reviewed the imaging and were able to discern the breast outline and distinguish fibroglandular tissue (FGT) from intramammary adipose tissue. Additionally, the expert readers agreed on their assessment of the breast tissue pattern including fatty, scattered FGT, heterogeneous FGT, and extreme FGT. This preliminary work demonstrates that ULF breast MRI is feasible and may be a potential option for comfortable, widely deployable, and low-cost breast cancer diagnosis and screening.
WITHDRAWN:Shewanellais a putative producer of polyunsaturated fatty acids in the gut soil of the composting earthwormEisenia fetida
Authors: Wittlinger Jan-Philipp , Castejón Natalia , Hausmann Bela , Berry David , Schnorr Stephanie L.
Published: April 2024

Withdrawal Statement

The authors have withdrawn this manuscript owing to a duplicate posting of manuscript number BIORXIV/2024/587473. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author. The correct preprint can be found at doi.org/10.1101/2024.03.31.587473.
Medical ChatGPT – A systematic Meta-Review
Authors: Egger Jan , Sallam Malik , Luijten Gijs , Gsaxner Christina , Pepe Antonio , Kleesiek Jens , Puladi Behrus , Li Jianning
Published: April 2024

Since its release at the end of 2022, ChatGPT has seen a tremendous rise in attention, not only from the general public, but also from medical researchers and healthcare professionals. ChatGPT definitely changed the way we can communicate now with computers. We still remember the limitations of (voice) assistants, like Alexa or Siri, that were “overwhelmed” by a follow-up question after asking about the weather, not to mention even more complex questions, which they could not handle at all. ChatGPT and other Large Language Models (LLMs) turned that in the meantime upside down. They allow fluent and continuous conversations on a human-like level with very complex sentences and diffused in the meantime into all kinds of applications and areas. One area that was not spared from this development, is the medical domain. An indicator for this is the medical search engine PubMed, which comprises currently more than 36 million citations for biomedical literature from MEDLINE, life science journals, and online books. As of March 2024, the search term “ChatGPT” already returns over 2,700 results. In general, it takes some time, until reviews, and especially systematic reviews appear for a “new” topic or discovery. However, not for ChatGPT, and the additional search restriction to “systematic review” for article type under PubMed, returns still 31 contributions, as of March 19 2024. After filtering out non-systematic reviews from the returned results, 19 publications are included. In this meta-review, we want to take a closer look at these contributions on a higher level and explore the current evidence of ChatGPT in the medical domain, because systematic reviews belong to the highest form of knowledge in science.
Increasing the accuracy of exchange parameters reporting on slow dynamics by performing CEST experiments with highB1fields
Authors: Khandave Nihar Pradeep , Hansen D Flemming , Vallurupalli Pramodh
Published: April 2024

Over the last decade chemical exchange saturation transfer (CEST) NMR methods have emerged as powerful tools to characterize biomolecular conformational dynamics occurring between a visible major state and ‘invisible’ minor states. The ability of the CEST experiment to detect these minor states, and provide precise exchange parameters, hinges on using appropriateB1field strengths during the saturation period. Typically, a pair ofB1fields withω1(= 2πB1) values around the exchange ratekexare chosen. Here we show that the transverse relaxation rate of the minor state resonance (R2,B) also plays a crucial role in determining theB1fields that lead to the most informative datasets. Using, to guide the choice ofB1, instead ofkex, leads to data wherefrom substantially more accurate exchange parameters can be derived. The need for higherB1fields, guided by K, is demonstrated by studying the conformational exchange in two mutants of the 71 residue FF domain withkex∼11 s-1and ∼72 s-1, respectively. In both cases analysis of CEST datasets recorded usingB1field values guided bykexlead to imprecise exchange parameters, whereas usingB1values guided by K resulted in precise site-specific exchange parameters. The conclusions presented here will be valuable while using CEST to study slow processes at sites with large intrinsic relaxation rates, including carbonyl sites in small to medium sized proteins, amide15N sites in large proteins and when the minor state dips are broadened due to exchange among the minor states.
Palynological studies on the selected members ofFabaceae
Authors: Pranav Raj T.K. , Ajin Shaju , Abhinna B.S. , Jojo Joseph
Published: April 2024

The investigation into pollen biology encompasses various stages such as pollen production, transfer to stigma, and the ensuing interactions leading to fertilization. Stigma plays a crucial role in providing an optimal environment for pollen germination and subsequent tube growth. However, conductingin vivostudies presents challenges due to the complexities of pistillate tissues, thus necessitating a reliance onin vitrocultures to comprehend pollen physiology. This study focuses on assessing pollen viability and germination in a selection ofFabaceaespecies, includingCanavalia gladiata, Centrosoma pubescens, Clitoria ternatea, Crotalaria pallida, Glyricidia maculata, Pueraria phaseoloides, andVigna unguiculata, utilizing tetrazolium testing and hanging drop culture methods. Results demonstrate a range of variability in pollen viability (from 19.38% to 80.78%) and germination (ranging from 23.90% to 79.81%), withCrotalaria pallidaexhibiting the highest rates of viability and germination, whereasClitoria ternateaandPueraria phaseoloidesdisplayed the lowest rates. This investigation contributes valuable insights into the pollen characteristics ofFabaceaespecies, hinting at possible connections between pollen viability/germination and seed/fruit set percentages.
SlAN1 is a limiting factor for the light-dependent anthocyanin accumulation in fruit tissues of purple tomato
Authors: Reis Gabriel Lasmar dos , Vaz Chaiane Fernandes , Arge Luis Willian Pacheco , Santos Adolfo Luís dos , Chaves-Silva Samuel , Peres Lázaro Eustáquio Pereira , Chalfun-Junior Antonio , Benedito Vagner Augusto
Published: April 2024

Anthocyanins are specialized plant metabolites with significant dietary value due to their anti-inflammatory properties. Research indicates that dietary intake of these phenolic compounds contributes to preventing various chronic diseases. As the most consumed vegetable worldwide, tomato (Solanum lycopersicum) is an excellent candidate for anthocyanin-enrichment strategies. In tomato, activation of anthocyanin biosynthesis is light-dependent, but this mechanism has yet to be entirely characterized. We investigated the role of light in anthocyanin biosynthesis in fruits of the purple tomato, which is a near-isogenic line (NIL) derived from wild accessions into cv. Micro-Tom (MT). MT-Aft/atv/hp2starts accumulating anthocyanin early during fruit development but is restricted to the peel (exocarp and epicarp). Manipulating light incidence in different fruit tissues determined that the absence of anthocyanin accumulation in the flesh results from the sun-blocking effect of the cyanic epicarp on the mesocarp, thus preventing light from penetrating deeper into the fruit. Transcriptional analyses of the fruit peel and flesh revealed that the bHLH transcription factor SlAN1 (Solyc09g065100) is the limiting factor for light-dependent anthocyanin accumulation in both tissues. This research enhances our comprehension of the genetic and environmental regulation of anthocyanin accumulation in fruit tissues, offering valuable insights into plant breeding for human nutrition.

Highlight

The expression of theSlAN1gene is activated in response to light signals, and it is the limiting factor for anthocyanin pigmentation in tomato fruit tissues.
Mosaic and cocktail capsid-virus-like particle vaccines for induction of antibodies against the EPCR-binding CIDRα1 domain of PfEMP1
Authors: Riedmiller Ilary , Fougeroux Cyrielle , Jensen Rasmus W. , Kana Ikhlaq H. , Sander Adam F. , Theander Thor G. , Lavstsen Thomas , Turner Louise
Published: April 2024

The sequestration ofPlasmodium falciparum-infected erythrocytes to the host endothelium is central to the pathogenesis of malaria. The sequestration is mediated by the parasités diversePlasmodium falciparumerythrocyte membrane protein 1 (PfEMP1) variants, which bind select human receptors on the endothelium. Severe malaria is associated with PfEMP1 binding human endothelial protein C receptor (EPCR) via their CIDRα1 domains. Antibodies binding and inhibiting across the sequence diverse CIDRα1 domains are likely important in acquired immunity against severe malaria. In this study, we explored if immunization with AP205 bacteriophage capsid-virus-like particles (cVLPs) presenting a mosaic of diverse CIDRα1 protein variants would stimulate broadly reactive and inhibitory antibody responses in mice. Three different mosaic cVLP vaccines each composed of five CIDRα1 protein variants with varying degrees of sequence conservation of residues at and near the EPCR binding site, were tested. All mosaic cVLP vaccines induced functional antibodies comparable to those induced by matched cocktails of cVLPs decorated with the single CIDRα1 variant. No broadly reactive responses were observed. However, the vaccines did induce some cross-reactivity and inhibition within the CIDRα1 subclasses included in the vaccines, demonstrating potential use of the cVLP vaccine platform for the design of multivalent vaccines.
Alanine-scanning mutagenesis library of MreB reveals distinct roles for regulating cell shape and viability
Authors: Maharjan Suman , Sloan Ryan , Lusk Jada , Bevienguevarr Rose , Surber Jacob , Morgenstein Randy M.
Published: April 2024

The bacterial actin-homolog MreB is a crucial component of the rod-system (elongasome) that maintains rod shape in many bacteria. It is localized beneath the inner membrane where it organizes the elongasome complex. Depletion or deletion ofmreBresults in loss of rod shape and cell death; however, the mechanism of how MreB operates is not known, given that the protein cannot be purified in a functionally intact form. Past studies have reported mutations inmreBcause varying degrees of cell shape and size alterations based on the type and position of the substitution. To better understand the role of MreB in rod shape formation we have taken the first truly systematic approach by replacing the native copy ofmreBwith an alanine-scanning mutagenesis library. Surprisingly, we observed stably growing spherical mutants that have lost MreB’s function(s) for shape regulation without losing viability. Hence, MreB has vital functions related to growth in addition to shape maintenance that can be separated. In support of this, rod shape suppressor analysis of these spherical mutants only revealed reversions or intragenicmreBmutations, suggesting that MreB is indispensable for rod shape. Additionally, our results imply the elongasome is no longer active in these strains, suggesting a novel way for rod shaped bacteria to synthesize cell wall.
Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration
Authors: Liu Dong , Webber Hannah C. , Bian Fuyun , Xu Yangfan , Prakash Manjari , Feng Xue , Yang Ming , Yang Hang , You In-Jee , Li Liang , Liu Liping , Liu Pingting , Huang Haoliang , Chang Chien-Yi , Liu Liang , Shah Sahil H , Torre Anna La , Welsbie Derek S. , Sun Yang , Duan Xin , Goldberg Jeffrey Louis , Braun Marcus , Lansky Zdenek , Hu Yang
Published: April 2024

Optineurin (OPTN) mutations are linked to amyotrophic lateral sclerosis (ALS) and normal tension glaucoma (NTG), but a relevant animal model is lacking, and the molecular mechanisms underlying neurodegeneration are unknown. We found that OPTN C-terminus truncation (OPTNΔC) causes late-onset neurodegeneration of retinal ganglion cells (RGCs), optic nerve (ON), and spinal cord motor neurons, preceded by a striking decrease of axonal mitochondria. Surprisingly, we discover that OPTN directly interacts with both microtubules and the mitochondrial transport complex TRAK1/KIF5B, stabilizing them for proper anterograde axonal mitochondrial transport, in a C- terminus dependent manner. Encouragingly, overexpressing OPTN/TRAK1/KIF5B reverses not only OPTN truncation-induced, but also ocular hypertension-induced neurodegeneration, and promotes striking ON regeneration. Therefore, in addition to generating new animal models for NTG and ALS, our results establish OPTN as a novel facilitator of the microtubule-dependent mitochondrial transport necessary for adequate axonal mitochondria delivery, and its loss as the likely molecular mechanism of neurodegeneration.