bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell profiling reveals Müller glia coordinate retinal intercellular communication during light/dark adaptation via thyroid hormone signaling
Authors: Wei Min , Sun Yanping , Li Shouzhen , Chen Yunuo , Li Longfei , Fang Minghao , Shi Ronghua , Tong Dali , Chen Jutao , Ma Yuqian , Qu Kun , Zhang Mei , Xue Tian
Published: February 2023

Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.
A Welfare Analysis of Occupational Licensing in U.S. States
Authors: Kleiner Morris M , Soltas Evan J
Published: February 2023

We assess the welfare consequences of occupational licensing for workers and consumers. We estimate a model of labour market equilibrium in which licensing restricts labour supply but also affects labour demand via worker quality and selection. On the margin of occupations licensed differently between U.S. states, we find that licensing raises wages and hours but reduces employment. We estimate an average welfare loss of 12% of occupational surplus. Workers and consumers respectively bear 70% and 30% of the incidence. Higher willingness to pay offsets 80% of higher prices for consumers, and higher wages compensate workers for 60% of the cost of mandated investment in occupation-specific human capital. Welfare effects appear more favourable in occupations in which licensing is more common.
Wet cupping therapy in the modulation of inflammation in patients with pain
Authors: Al Jaouni Soad K , Rohaiem Sawsan M , Almuhayawi Mohammed S , Godugu Kavitha , Almughales Jamil , Kholi Sabria M , Al-Raddadi Rajaa , Bukhari Musab , Mousa Shaker A
Published: February 2023

Objectives

Wet cupping therapy (WCT) is a complementary treatment used for a wide range of diseases associated with pain. Inflammatory cytokines play an important role in the clinical symptoms related to pain. The objective of this study is to assess the changes in inflammatory markers (different interleukins (IL) and tumour necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte stimulating factor (G-CSF)) in patients with pain who went a 6 weeks of WCT as a complementary approach.

Methods

This is a retrospective record review study from the Prophetic Medicine Clinics for Cupping Therapy Clinics, at King Abdulaziz University Hospital, Saudi Arabia. It consists of 93 adult patients; these patients were referred from different specialty clinics with various diagnoses due to pain for performing WCT as an integrative treatment. Measurements of various biomarkers in patients with pain before and after 6 weeks of WCT were carried out.

Key findings

Serum IL-1β, IL-5, IL-6, IL-7, IL-8, IL-12, IL-13, TNF-α, GM-CSF, G-CSF, MCP-1 and MIP-1β were significantly (P < 0.001) decreased in patients after 6 weeks of WCT. Other biomarkers did not significantly change.

Conclusions

WCT showed favourable effects on pro-inflammatory markers (cytokines and chemokines) in patients with pain.
Cost and cost-effectiveness analysis of a digital diabetes prevention program: results from the PREDICTS trial
Authors: Michaud Tzeyu L , Wilson Kathryn E , Katula Jeffrey A , You Wen , Estabrooks Paul A
Published: February 2023

Although technology-assisted diabetes prevention programs (DPPs) have been shown to improve glycemic control and weight loss, information are limited regarding relevant costs and their cost-effectiveness. To describe a retrospective within-trial cost and cost-effectiveness analysis (CEA) to compare a digital-based DPP (d-DPP) with small group education (SGE), over a 1-year study period. The costs were summarized into direct medical costs, direct nonmedical costs (i.e., times that participants spent engaging with the interventions), and indirect costs (i.e., lost work productivity costs). The CEA was measured by the incremental cost-effectiveness ratio (ICER). Sensitivity analysis was performed using nonparametric bootstrap analysis. Over 1 year, the direct medical costs, direct nonmedical costs, and indirect costs per participant were $4,556, $1,595, and $6,942 in the d-DPP group versus $4,177, $1,350, and $9,204 in the SGE group. The CEA results showed cost savings from d-DPP relative to SGE based on a societal perspective. Using a private payer perspective for d-DPP, ICERs were $4,739 and $114 to obtain an additional unit reduction in HbA1c (%) and weight (kg), and were $19,955 for an additional unit gain of quality-adjusted life years (QALYs) compared to SGE, respectively. From a societal perspective, bootstrapping results indicated that d-DPP has a 39% and a 69% probability, at a willingness-to-pay of $50,000/QALY and $100,000/QALY, respectively, of being cost-effective. The d-DPP was cost-effective and offers the prospect of high scalability and sustainability due to its program features and delivery modes, which can be easily translated to other settings.
Populusroot salicinoid phenolic glycosides are not mobilized to support metabolism and regrowth under carbon-limited conditions
Authors: Hillabrand R M , Gordon H , Hynes B , Constabel C P , Landhäusser S M
Published: February 2023

Remobilization of carbon storage compounds in trees is crucial for the resilience to disturbances, stress and the requirements of their perennial lifestyle, all of which can impact photosynthetic carbon gain. Trees contain abundant non-structural carbohydrates in the form of starch and sugars for long-term carbon storage, yet questions remain about the ability of trees to remobilize non-conventional carbon compounds under stress. Aspens, like other members of the genus Populus, have abundant specialized metabolites called salicinoid phenolic glycosides, which contain a core glucose moiety. In this study, we hypothesized that the glucose-containing salicinoids could be remobilized as an additional carbon source during severe carbon limitation. We made use of genetically modified hybrid aspen (Populus tremula L.× Populus albaL.) with minimal salicinoid content and compared these with control plants with high salicinoid content during resprouting (suckering) in dark (carbon-limited) conditions. As salicinoids are abundant anti-herbivore compounds, identification of such a secondary function for salicinoids may provide insight into the evolutionary pressures that drive their accumulation. Our results show that salicinoid biosynthesis is maintained during carbon limitation and suggests that salicinoids are not remobilized as a carbon source for regenerating shoot tissue. However, we found that salicinoid-producing aspens had reduced resprouting capacity per available root biomass when compared with salicinoid-deficient aspens. Therefore, our work shows that the constitutive salicinoid production in aspens can reduce the capacity for resprouting and survival in carbon-limited conditions.
A Revised Nomenclature for ToxA Haplotypes Across Multiple Fungal Species
Authors: Aboukhaddour Reem , Hafez Mohamed , McDonald Megan , Moffat Caroline S. , Navathe Sudhir , Friesen Timothy L. , Strelkov Stephen E. , Oliver Richard P. , Tan Kar-Chun , Liu Zhaohui , Moolhuijzen Paula M. , Phan Huyen , See Pao Theen , Solomon Peter S.
Published: February 2023

ToxA is one of the most studied proteinaceous necrotrophic effectors produced by plant pathogens. It has been identified in four pathogens ( Pyrenophora tritici-repentis, Parastagonospora nodorum, Parastagonospora pseudonodorum [formerly Parastagonospora avenaria f. sp. tritici], and Bipolaris sorokiniana) causing leaf spot diseases on cereals worldwide. To date, 24 different ToxA haplotypes have been identified. Some P. tritici-repentis and related species also express ToxB, another small protein necrotrophic effector. We present here a revised and standardized nomenclature for these effectors, which could be extended to other poly-haplotypic genes found across multiple species.
OASL knockdown inhibits the progression of stomach adenocarcinoma by regulating the mTORC1 signaling pathway
Authors: Zhao Weizhu , Yang Haiying , Liu Luguang , Qu Xianlin , Ding Jishuang , Yu Hang , Xu Botao , Zhao Siwei , Xi Guangmin , Xing Ligang , Chai Jie
Published: February 2023

The present study investigated the effects of 2′‐5′ oligoadenylate synthetase‐like (OASL) on the biological functions of stomach adenocarcinoma (STAD) cells and tumor formation in nude mice. The differential expression levels of OASL in the different cancer types from TCGA dataset were analyzed using gene expression profiling interactive analysis. Overall survival and the receiver operating characteristic were analyzed using the KM plotter and R, respectively. Furthermore, OASL expression and its effects on the biological functions of STAD cells were detected. The possible upstream transcription factors of OASL were predicted using JASPAR. The downstream signaling pathways of OASL were analyzed using GSEA. Tumor formation experiments were performed to evaluate the effect of OASL on tumor formation in nude mice. The results showed that OASL was highly expressed in STAD tissues and cell lines. OASL knockdown markedly inhibited cell viability, proliferation, migration, and invasion and accelerated STAD cell apoptosis. Conversely, OASL overexpression had the opposite effect on STAD cells. JASPAR analysis revealed that STAT1 is an upstream transcription factor of OASL. Furthermore, GSEA showed that OASL activated the mTORC1 signaling pathway in STAD. The protein expression levels of p‐mTOR and p‐RPS6KB1 were suppressed by OASL knockdown and promoted by OASL overexpression. The mTOR inhibitor, rapamycin, markedly reversed the effect of OASL overexpression on STAD cells. Additionally, OASL promoted tumor formation and increased tumor weight and volume in vivo. In conclusion, OASL knockdown suppressed the proliferation, migration, invasion, and tumor formation of STAD cells by inhibiting the mTOR signaling pathway.
Mediation of serum albumin in the association of serum potassium with mortality in Chinese dialysis patients: a prospective cohort study
Authors: Huang Naya , Liu Yuanying , Ai Zhen , Zhou Qian , Mao Haiping , Yang Xiao , Xu Yuanwen , Yu Xueqing , Chen Wei
Published: February 2023

Background:

The clinical importance of hypokalemia is likely underrecognized in Chinese dialysis patients, and whether its clinical effect was mediated by serum albumin is not fully elucidated. This study aimed to explore the association between serum.

Methods:

This was a prospective nation-wide multicenter cohort study. Restricted cubic splines were used to test the linearity of serum potassium and relationships with all-cause (AC) and cardiovascular (CV) mortality and a subsequent two-line piecewise linear model was fitted to approach the nadir. A mediation analysis was performed to examine relations of albumin to potassium and mortalities.

Results:

A total of 10,027 patients were included, of whom 6605 were peritoneal dialysis and 3422 were hemodialysis patients. In the overall population, the mean age was 51.69 ± 14.8 years, 55.3%(5546/10027) were male, and the median dialysis vintage was 13.60 (4.70, 39.70) months. Baseline serum potassium was 4.30 ± 0.88 mmol/L. After a median follow-up period of 26.87 (14.77, 41.50) months, a U-shaped was found between potassium and mortality, and a marked increase in risk at lower potassium but a moderate elevation in risk at higher potassium were observed. The nadir for AC mortality risk was estimated from piecewise linear models to be a potassium concentration of 4.0 mmol/L. Interestingly, the significance of the association between potassium and mortality was attenuated when albumin was introduced into the extended adjusted model. A subsequent significant mediation by albumin for potassium and AC and CV mortalities were found (P < 0.001 for both), indicating that hypokalemia led to higher mortality mediated by low serum albumin, which was a surrogate of poor nutritional status and inflammation.

Conclusions:

Associations between potassium and mortalities were U-shaped in the overall population. The nadir for AC mortality risk was at a potassium of 4.0 mmol/L. Serum albumin mediated the association between potassium and AC and CV mortalities.
A multicenter, randomized, placebo-controlled study to select the minimum effective dose of estetrol in postmenopausal participants (E4Relief): part 2—vaginal cytology, genitourinary syndrome of menopause, and health-related quality of life
Authors: Gaspard Ulysse , Taziaux Mélanie , Jost Maud , Coelingh Bennink Herjan J.T. , Utian Wulf H. , Lobo Rogerio A. , Foidart Jean-Michel
Published: February 2023

Objective

A phase 2 study showed that 15 mg estetrol (E4) alleviates vasomotor symptoms (VMS). Here, we present the effects of E4 15 mg on vaginal cytology, genitourinary syndrome of menopause, and health-related quality of life.

Methods

In a double-blind, placebo-controlled study, postmenopausal participants (n = 257, 40-65 y) were randomized to receive E4 2.5, 5, 10, or 15 mg or placebo once daily for 12 weeks. Outcomes were the vaginal maturation index and maturation value, genitourinary syndrome of menopause score, and the Menopause Rating Scale to assess health-related quality of life. We focused on E4 15 mg, the dose studied in ongoing phase 3 trials, and tested its effect versus placebo at 12 weeks using analysis of covariance.

Results

Least square (LS) mean percentages of parabasal and intermediate cells decreased, whereas superficial cells increased across E4 doses; for E4 15 mg, the respective changes were −10.81% (P = 0.0017), −20.96% (P = 0.0037), and +34.17% (P < 0.0001). E4 15 mg decreased LS mean intensity score for vaginal dryness and dyspareunia (−0.40, P = 0.03, and −0.47, P = 0.0006, respectively); symptom reporting decreased by 41% and 50%, respectively, and shifted to milder intensity categories. The overall Menopause Rating Scale score decreased with E4 15 mg (LS mean, −3.1; P = 0.069) and across doses was associated with a decreasing frequency and severity of VMS (r = 0.34 and r = 0.31, P < 0.001).

Conclusions

E4 demonstrated estrogenic effects in the vagina and decreased signs of atrophy. E4 15 mg is a promising treatment option also for important menopausal symptoms other than VMS.
Lipoabdominoplasty: What We Have Implemented and What We Have Modified over 26 Years
Authors: Cárdenas-Camarena Lázaro , Reyes-Herrera Martín Fernando , Vargas-Flores Edgar , López-Fabila Daniel Atl , Robles-Cervantes José Antonio
Published: February 2023

Lipoabdominoplasty is one of the most commonly performed procedures in body-contouring surgery. We present a retrospective study of our 26 years of experience to improve the results and assure the greatest possible safety in lipoabdominoplasty. We include all of our female patients who underwent lipoabdominoplasty performed from July 1996 to June 2022, dividing the patients into two groups: group I underwent circumferential liposuction avoiding abdominal flap liposuction for the first 7 years, and group II underwent circumferential liposuction including abdominal flap liposuction for the subsequent 19 years, pointing out the differences in the processes, results, and complications of both groups. Over a period of 26 years, 973 female patients underwent lipoabdominoplasty: 310 in group I and 663 in group II. Ages were very similar; however, weight, BMI, amount of liposuction material, and weight of the abdominal flap removed were higher in group I. Twenty percent of patients in group I were obese compared to 7% in group II. The average amount of liposuction in group I was 4990 mL compared to 3373 mL in group II and 1120 g of abdominal flap in group I versus 676 g in group II. Minor and major complications were 11.6% and 1.2% in group I versus 9.2% and 0.6% in group II, respectively. In our more than 26 years of performing lipoabdominoplasty, we have maintained most of our initial procedures. These processes have allowed us to perform surgery safely and effectively with a low morbidity rate.
A Multicenter Noninferiority Study Comparing Safety and Effectiveness of Hyaluronic Acid Fillers for Correction of Nasolabial Folds in Chinese Subjects
Authors: Li Wenzhi , Li Bi , Hofmann Matthias , Klein Gudrun , Xie Hongfu
Published: February 2023

Background:

Hyaluronic acid fillers are the preferred choice for minimally invasive facial volume restoration. In this study, a split-face design was used to compare the effectiveness and safety results of Belotero Balance Lidocaine (BEL) and Restylane (RES, control) to investigate whether BEL is noninferior compared with RES in nasolabial fold (NLF) correction.

Methods:

This was a prospective, controlled clinical study in Chinese subjects. Subjects with symmetrical moderate NLFs according to the Wrinkle Severity Rating Scale were randomized to receive BEL in one NLF and RES in the other. The primary objective was to investigate whether BEL is noninferior compared with RES after being injected mid-dermally in moderate NLFs after 6 months. Secondary objectives included responses at other visits and pain sensation. Treatment-emergent adverse events (TEAEs) were assessed.

Results:

A total of 220 subjects were enrolled. The Wrinkle Severity Rating Scale response rates at month 6 were 62.9% for BEL versus 64.9% for RES, demonstrating noninferiority. The secondary endpoints supported this. Significantly reduced pain scores were observed for BEL versus RES. For both products, injection site nodule and bruising were the most frequent treatment-emergent adverse events at the injection site. All treatment-related treatment-emergent adverse events were mild.

Conclusions:

The study showed that BEL is effective and well tolerated for correction of moderate NLFs in Chinese subjects. Noninferiority of BEL was demonstrated compared with RES, and regardless of applied pain treatment, a further reduction in injection pain was observed in BEL.
Burden of fatty liver and hepatic fibrosis in persons with HIV: A diverse cross-sectional US multicenter study
Authors: Gawrieh Samer , Lake Jordan E. , Debroy Paula , Sjoquist Julia A. , Robison Montreca , Tann Mark , Akisik Fatih , Bhamidipalli Surya S. , Saha Chandan K. , Zachary Kimon , Robbins Gregory K. , Gupta Samir K. , Chung Raymond T. , Chalasani Naga , Corey Kathleen E.
Published: February 2023

Background & Aims:

The current prevalence of fatty liver disease (FLD) due to alcohol-associated (AFLD) and nonalcoholic (NAFLD) origins in US persons with HIV (PWH) is not well defined. We prospectively evaluated the burden of FLD and hepatic fibrosis in a diverse cohort of PWH.

Approach & Results:

Consenting participants in outpatient HIV clinics in 3 centers in the US underwent detailed phenotyping, including liver ultrasound and vibration-controlled transient elastography for controlled attenuation parameter and liver stiffness measurement. The prevalence of AFLD, NAFLD, and clinically significant and advanced fibrosis was determined. Univariate and multivariate logistic regression models were used to evaluate factors associated with the risk of NAFLD. Of 342 participants, 95.6% were on antiretroviral therapy, 93.9% had adequate viral suppression, 48.7% (95% CI 43%–54%) had steatosis by ultrasound, and 50.6% (95% CI 45%–56%) had steatosis by controlled attenuation parameter ≥263 dB/m. NAFLD accounted for 90% of FLD. In multivariable analysis, old age, higher body mass index, diabetes, and higher alanine aminotransferase, but not antiretroviral therapy or CD4+ cell count, were independently associated with increased NAFLD risk. In all PWH with fatty liver, the frequency of liver stiffness measurement 8–12 kPa was 13.9% (95% CI 9%–20%) and ≥12 kPa 6.4% (95% CI 3%–11%), with a similar frequency of these liver stiffness measurement cutoffs in NAFLD.

Conclusions:

Nearly half of the virally-suppressed PWH have FLD, 90% of which is due to NAFLD. A fifth of the PWH with FLD has clinically significant fibrosis, and 6% have advanced fibrosis. These data lend support to systematic screening for high-risk NAFLD in PWH.
Prediction of Nonrelapse Mortality in Patients With Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia Receiving Allogeneic Stem Cell Transplantation With Posttransplantation Cyclophosphamide-based Graft Versus Host Disease Prophylaxis
Authors: Hermans Sjoerd J. F. , Versluis Jurjen , Labopin Myriam , Giebel Sebastian , van Norden Yvette , Moiseev Ivan , Blaise Didier , Díez Martín Jose L. , Meijer Ellen , Rovira Montserrat , Choi Goda , Raiola Anna Maria , Koc Yener , Reményi Péter , Vydra Jan , Kröger Nicolaus , Sica Simona , Martino Massimo , van Gorkom Gwendolyn , Chevallier Patrice , Busca Alessandro , Herrera Arroyo Concepcion , Brissot Eolia , Peric Zinaida , Nagler Arnon , Shouval Roni , Ciceri Fabio , Cornelissen Jan J. , Mohty Mohamad
Published: February 2023

Graft versus host disease (GVHD) prophylaxis with posttransplantation cyclophosphamide (PTCY) has been established to reduce severe GVHD, and thereby potentially reducing nonrelapse mortality (NRM) after allogeneic stem cell transplantation (alloSCT). We evaluated the predictive capacity of established NRM-risk scores in patients receiving PTCY-based GVHD prophylaxis, and subsequently developed and validated a novel PTCY-specific NRM-risk model. Adult patients (n = 1861) with AML or ALL in first complete remission who received alloSCT with PTCY-based GVHD prophylaxis were included. The PTCY-risk score was developed using multivariable Fine and Gray regression, selecting parameters from the hematopoietic cell transplantation-comorbidity index (HCT-CI) and European Group for Blood and Marrow Transplantation (EBMT) score with a subdistribution hazard ratio (SHR) of ≥1.2 for 2-year NRM in the training set (70% split), which was validated in the test set (30%). The performance of the EBMT score, HCT-CI, and integrated EBMT score was relatively poor for discriminating 2-year NRM (c-statistic 51.7%, 56.6%, and 59.2%, respectively). The PTCY-risk score included 10 variables which were collapsed in 3 risk groups estimating 2-year NRM of 11% ± 2%, 19% ± 2%, and 36% ± 3% (training set, c-statistic 64%), and 11% ± 2%, 18% ± 3%, and 31% ± 5% (test set, c-statistic 63%), which also translated into different overall survival. Collectively, we developed an NRM-risk score for acute leukemia patients receiving PTCY that better predicted 2-year NRM compared with existing models, which might be applicable to the specific toxicities of high-dose cyclophosphamide.
Sharps Injury Rates Reported Among US Workers
Authors: Kennedy Erika J. , Hendricks Kitty J. , Casey Megan
Published: February 2023

Objective

To examine sharps injury (SI) rates among US workers treated in hospital emergency departments.

Methods

A national probability-based sample of approximately 67 US hospital emergency departments from the National Electronic Injury Surveillance System—Occupational Supplement was used to examine annual national estimates of SI rates (number of injuries/10,000 full-time equivalents) for US workers from 2006 to 2020.

Results

Among the general US worker population, the 25- to 34-year age group experienced the highest annual SI rate. Health care industry workers experienced SI rates up to 16 times the rate of all US workers.

Conclusion

Younger age (≤34 years) is associated with increased SI risk. Tailored prevention efforts should be developed to address the specific needs of these workers, especially among health care workers. Continual occupational surveillance will maximize the health and safety of US workers.
Pediatric musculoskeletal infections
Authors: Hannon Megan , Lyons Todd
Published: February 2023

Purpose of review

The aim of this article is to review the recent guidelines and literature regarding the diagnosis and the treatment of common pediatric musculoskeletal infections: septic arthritis, osteomyelitis, pyomyositis, and Lyme disease.

Recent findings

In the last decade, a better understanding of the causative organisms of common bacterial infections, including Kingella, leads to prompt targeted antimicrobial coverage in all musculoskeletal infections. Prompt diagnosis and treatment continues to be the mainstay in the treatment of children with osteoarticular infections. Efforts to improve early detection have lead to improving rapid lab diagnostic testing; however, more advanced diagnostics such as arthrocentesis for septic arthritis and MRI for osteomyelitis and pyomyositis, remain the gold standard. Shorter and narrowed antibiotic courses, with appropriate transition to outpatient oral treatment provide effective infection clearance and reduction in complications of disease.

Advances in diagnostics, including pathogen identification as well as imaging continues to improve our ability to diagnose and treat these infections, although still lack ability to provide definitive diagnosis without more invasive nor advanced techniques.
Communication Frameworks for Palliative Surgical Consultations
Authors: Blumenthaler Alisa N. , Robinson Kristen Ashlee , Hodge Caitlin , Xiao Lianchun , Lilley Elizabeth J. , Griffin James F. , White Michael G. , Day Ryan , Tanco Kimberson , Bruera Eduardo , Badgwell Brian D.
Published: February 2023

Objective:

To evaluate whether patients with advanced cancer prefer surgeons to use the best case/worst case (BC/WC) communication framework over the traditional risk/benefit (R/B) framework in the context of palliative surgical scenarios.

Background:

Identifying the patient’s preferred communication frameworks may improve satisfaction and outcome measures during difficult clinical decision-making.

Methods:

In a video-vignette–based randomized, double-blinded study from November 2020 to May 2021, patients with advanced cancer viewed 2 videos depicting a physician-patient encounter in a palliative surgical scenario, in which the surgeon uses either the BC/WC or the R/B framework to discuss treatment options. The primary outcome was the patients’ preferred video surgeon.

Results:

One hundred fifty-five patients were approached to participate; 66 were randomized and 58 completed the study (mean age 55.8 ± 13.8 years, 60.3% males). 22 patients (37.9%, 95% CI: 25.4%–50.4%) preferred the surgeon using the BC/WC framework, 21 (36.2%, 95% CI: 23.8%–48.6%) preferred the surgeon using the R/B framework, and 15 (25.9%, 95% CI: 14.6%–37.2%) indicated no preference. High trust in the medical profession was inversely associated with a preference for the surgeon using BC/WC framework (odds ratio: 0.83, 95% CI: 0.70–0.98, P = 0.03). The BC/WC framework rated higher for perceived surgeon’s listening (4.6 ± 0.7 vs 4.3±0.9, P = 0.03) and confidence in the surgeon’s trustworthiness (4.3 ± 0.8 vs 4.0 ± 0.9, P = 0.04).

Conclusions:

Surgeon use of the BC/WC communication framework was not universally preferred but was as acceptable to patients as the traditional R/B framework and rated higher in certain aspects of communication. A preference for a surgeon using BC/WC was associated with lower trust in the medical profession. Surgeons should consider the BC/WC framework to individualize their approach to challenging clinical discussions.
Differences in Sexual and Physical Abuse History by Presenting Chief Complaint in an Outpatient Urogynecology Population
Authors: Hansbarger Molly , Ackenbom Mary , Shepherd Jonathan P.
Published: February 2023

Importance

One in 3 women experience sexual or physical violence in their lifetimes. Health consequences for survivors are numerous, including urogynecologic symptoms.

Objectives

We aimed to determine prevalence and factors that predict a history of sexual or physical abuse (SA/PA) in outpatient urogynecology, specifically whether the chief complaint (CC) predicts a history of SA/PA.

Study Design

This cross-sectional study analyzed 1,000 newly presenting patients to 1 of 7 urogynecology offices in western Pennsylvania from November 2014 to November 2015. All sociodemographic/medical data were retrospectively abstracted. Univariable and multivariable logistic regression analyzed risk factors based on known associated variables.

Results

One thousand new patients had a mean age of 58.4 ± 15.8 years with a body mass index (BMI) of 28.8 ± 6.5. Nearly 12% reported a history of SA/PA. Patients with CC of pelvic pain were more than twice as likely to report abuse compared with all other CCs (odds ratio [OR], 2.690; 95% confidence interval [CI], 1.576–4.592). Prolapse was the most common CC (36.2%) but had the lowest prevalence of abuse (6.1%). Nocturia was an additional urogynecologic variable predictive of abuse (OR, 1.162 per nightly episode; 95% CI, 1.033–1.308). Increasing BMI and decreasing age both increased the risk of SA/PA. Smoking conferred the highest likelihood of abuse history (OR, 3.676; 95% CI, 2.252–5.988).

Conclusions

Although those with a CC of prolapse were less likely to report abuse history, we recommend routine screening for all women. Pelvic pain was the most common CC among women reporting abuse. Special efforts should be made to screen those at higher risk with complaints of pelvic pain who are younger, smokers, with higher BMI, and with increased nocturia.
d-Mannose for Recurrent Urinary Tract Infection Prevention in Postmenopausal Women Using Vaginal Estrogen: A Randomized Controlled Trial
Authors: Lenger Stacy M. , Chu Christine M. , Ghetti Chiara , Durkin Michael J. , Jennings Zoe , Wan Fei , Sutcliffe Siobhan , Lowder Jerry L.
Published: February 2023

Importance

Further research is needed to determine whether d-mannose plus vaginal estrogen therapy (VET) is beneficial over VET alone for recurrent urinary tract infection (rUTI) prevention.

Objective

The aim of this study was to evaluate d-mannose efficacy for rUTI prevention in postmenopausal women using VET.

Study Design

We conducted a randomized controlled trial comparing d-mannose (2 g/d) with control. Participants were required to have a history of uncomplicated rUTIs and to remain on VET throughout the trial. They were followed up 90 days for incident UTIs. Cumulative UTI incidences were calculated by the Kaplan-Meier method and compared by Cox proportional hazards regression. For the planned interim analysis, P < 0.001 was considered statistically significant. Futility analysis was performed by generating post hoc conditional power for multiple scenarios.

Results

We evaluated 545 patients for frequent/recurrent UTIs from March 1, 2018, to January 18, 2020. Of these women, 213 had culture-proven rUTIs, 71 were eligible, 57 enrolled, 44 began their planned 90-day study period, and 32 completed the study. At interim analysis, the overall cumulative UTI incidence was 46.6%; 41.1% in the treatment arm (median time to first UTI, 24 days) and 50.4% in the control arm (median, 21 days); hazard ratio, 0.76; 99.9% confidence interval, 0.15–3.97. d-Mannose was well tolerated with high participant adherence. Futility analysis suggested the study lacked power to detect the planned (25%) or observed (9%) difference as statistically significant; the study was halted before conclusion.

Conclusions

d-Mannose is a well-tolerated nutraceutical, but further research is needed to determine whether d-mannose in combination with VET has a significant, beneficial effect beyond VET alone in postmenopausal women with rUTIs.
Carbohydrate Loading and Aspiration Risk in Bariatric Patients: Safety in Preoperative Enhanced Recovery Protocols
Authors: Huang Estella Y , Li Jonathan Z , Chung Daniel , Jacobsen Garth R , Sandler Bryan J , Wadhwa Anupama , Said Engy , Robbins Kimberly , Horgan Santiago , Broderick Ryan C
Published: February 2023

Background:

Enhanced recovery protocols (ERPs) have been developed to improve perioperative outcomes, however there is ongoing concern for aspiration with recent oral intake in patients with obesity, who may be predisposed to impaired GI motility and greater gastric volumes. We aim to study the safety of a 300mL pre-op carbohydrate loading drink prior to bariatric surgery.

Methods:

Data was collected prospectively from patients undergoing primary bariatric surgery. All bariatric patients at our institution are prescribed a proton pump inhibitor (PPI) for 4 weeks prior to surgery and undergo a screening pre-op EGD before surgery with a traditional 8-hour fast (NOCARB), followed by an intraoperative day-of-surgery EGD with carbohydrate loading (CARB) 2-4 hours prior to incision. Gastric volumes and pH are measured after being endoscopically suctioned via direct visualization during both settings.

Results:

We identified 203 patients, 94 patients (46.3%) in the CARB group, and 109 patients (53.7%) in the NOCARB group. The patients were 82.3% female with a mean age of 42.8 years and average BMI of 41.7 kg/m2. There was no difference in gastric volume between NOCARB and CARB (17.0 versus 16.1mL, p=0.59). The NOCARB group had lower pHs than the CARB group (2.8 versus 3.8, p=0.001). Subset analysis of 23 patients who had measurements on both screening and intra-op EGD revealed less gastric volumes in CARB patients (13.3 versus 18.3, p<0.0001).

Conclusion:

When included in an ERP, PPI use and preoperative carbohydrate loading 2-4 hours before bariatric surgery does not increase aspiration risk based on gastric volumes and pH and should be strongly considered in all eligible bariatric patients.
Whole-genome-based characterization of Campylobacter jejuni from human patients with gastroenteritis collected over an 18 year period reveals increasing prevalence of antimicrobial resistance
Authors: Ghielmetti Giovanni , Seth-Smith Helena M. B. , Roloff Tim , Cernela Nicole , Biggel Michael , Stephan Roger , Egli Adrian
Published: February 2023

Campylobacteriosis is the most common cause of acute gastrointestinal bacterial infection in Europe, with most infections linked to the consumption of contaminated food. While previous studies found an increasing rate of antimicrobial resistance (AMR) in

Campylobacter

spp. over the past decades, the investigation of additional clinical isolates is likely to provide novel insights into the population structure and mechanisms of virulence and drug resistance of this important human pathogen. Therefore, we combined whole-genome sequencing and antimicrobial-susceptibility testing of 340 randomly selected

Campylobacter jejuni

isolates from humans with gastroenteritis, collected in Switzerland over an 18 year period. In our collection, the most common multilocus sequence types (STs) were ST-257 (n=44), ST-21 (n=36) and ST-50 (n=35); the most common clonal complexes (CCs) were CC-21 (n=102), CC-257 (n=49) and CC-48 (n=33). High heterogeneity was observed among STs, with the most abundant STs recurring over the entire study period, while others were observed only sporadically. Source attribution based on ST assigned more than half of the strains to the ‘generalist’ category (n=188), 25  % as ‘poultry specialist’ (n=83), and only a few to ‘ruminant specialist’ (n=11) or ‘wild bird’ origin (n=9). The isolates displayed an increased frequency of AMR from 2003 to 2020, with the highest rates of resistance observed for ciprofloxacin and nalidixic acid (49.8 %), followed by tetracycline (36.9 %). Quinolone-resistant isolates carried chromosomal gyrA mutations T86I (99.4 %) and T86A (0.6 %), whereas tetracycline-resistant isolates carried tet(O) (79.8 %) or mosaic tetO/32/O (20.2 %) genes. A novel chromosomal cassette carrying several resistance genes, including aph(3')-III, satA and aad(6), and flanked by insertion sequence elements was detected in one isolate. Collectively, our data revealed an increasing prevalence of resistance to quinolones and tetracycline in

C. jejuni

isolates from Swiss patients over time, linked to clonal expansion of gyrA mutants and acquisition of the tet(O) gene. Investigation of source attribution suggests that infections are most likely related to isolates from poultry or generalist backgrounds. These findings are relevant to guide future infection prevention and control strategies.
The type-VI secretion system of the beneficial symbiont Vibrio fischeri
Authors: Guckes Kirsten R. , Miyashiro Tim I.
Published: February 2023

The mutualistic symbiosis between the Hawaiian bobtail squid Euprymna scolopes and the marine bacterium

Vibrio fischeri

is a powerful experimental system for determining how intercellular interactions impact animal–bacterial associations. In nature, this symbiosis features multiple strains of

V. fischeri

within each adult animal, which indicates that different strains initially colonize each squid. Various studies have demonstrated that certain strains of

V. fischeri

possess a type-VI secretion system (T6SS), which can inhibit other strains from establishing symbiosis within the same host habitat. The T6SS is a bacterial melee weapon that enables a cell to kill adjacent cells by translocating toxic effectors via a lancet-like apparatus. This review describes the progress that has been made in understanding the factors that govern the structure and expression of the T6SS in

V. fischeri

and its effect on the symbiosis.
Athlete deaths during the COVID-19 vaccination campaign: contextualisation of online information
Authors: Binkhorst Mathijs , Goldstein Daniel J.
Published: February 2023

Background and aim

Lay people and medical professionals have suggested a link between (mRNA) COVID-19 vaccination and a purported increase in sudden cardiac arrest (SCA) and death (SCD) among athletes. We aimed to compare the athlete death rate in 2021-2022 with pre-pandemic estimates and investigate the role of vaccination.

Methods

A comprehensive, much referenced, publicly available list of health issues, emergencies, and SCA/SCD in athletes from January 2021 to December 2022 was analysed. Demographic data, country, type of sport, vaccination status, and possible association between reported medical events and vaccination were evaluated for the complete set of athletes. The following data were specifically assessed for cases of SCD in young US athletes and compared to matched data from pre-pandemic studies: average annual SCD number, mean age, male/female ratio, sports with highest death toll, cause and scene of death, and relation to exercise. Descriptive statistics were used.

Results

The list contained 1653 entries. (Former) athletes, aged 5-86 years, from 99 countries, participated in 61 different sports. In multiple cases, causes of and circumstances surrounding medical events were irretrievable. Many cases involved non-cardiovascular, exercise-unrelated aetiologies. Vaccination details were scarce. In 63 (3.8%) cases, including 9 fatal events, there was a plausible association with COVID-19 vaccination. In US athletes aged 9-40 (mean 22.7) years, 166 SCD cases were identified (average 83/year), mainly in males (83%) and in football (39.8%) and basketball (16.9%). Main causes of death were non-cardiovascular exercise-unrelated (22.9%) or unknown (50.6%). Deaths primarily occurred at rest (32.5%) or under unknown circumstances (38.6%). SCD characteristics were similar to those of two pre-pandemic studies with comparable datasets.

Conclusion

SCD rate among young US athletes in 2021-2022 was comparable to pre-pandemic estimates. There is currently no evidence to substantiate a link between (mRNA) COVID-19 vaccination and SCD in (young) athletes.
Predicting seizure outcome after epilepsy surgery: do we need more complex models, larger samples, or better data?
Authors: Eriksson Maria H , Ripart Mathilde , Piper Rory J , Moeller Friederike , Das Krishna B , Eltze Christin , Cooray Gerald , Booth John , Whitaker Kirstie J , Chari Aswin , Sanfilippo Patricia Martin , Caballero Ana Perez , Menzies Lara , McTague Amy , Tisdall Martin M , Cross J Helen , Baldeweg Torsten , Adler Sophie , Wagstyl Konrad
Published: February 2023

Objective

The accurate prediction of seizure freedom after epilepsy surgery remains challenging. We investigated if 1) training more complex models, 2) recruiting larger sample sizes, or 3) using data-driven selection of clinical predictors would improve our ability to predict post-operative seizure outcome. We also conducted the first external validation of a machine learning model trained to predict post-operative seizure outcome.

Methods

We performed a retrospective cohort study of 797 children who had undergone resective or disconnective epilepsy surgery at a single tertiary center. We extracted patient information from medical records and trained three models – a logistic regression, a multilayer perceptron, and an XGBoost model – to predict one-year post-operative seizure outcome on our dataset. We evaluated the performance of a recently published XGBoost model on the same patients. We further investigated the impact of sample size on model performance, using learning curve analysis to estimate performance at samples up toN=2,000. Finally, we examined the impact of predictor selection on model performance.

Results

Our logistic regression achieved an accuracy of 72% (95% CI=68-75%, AUC=0.72), while our multilayer perceptron and XGBoost both achieved accuracies of 71% (95% CIMLP=67-74%, AUCMLP=0.70; 95% CIXGBoost own=68-75%, AUCXGBoost own=0.70). There was no significant difference in performance between our three models (allP>0.4) and they all performed better than the external XGBoost, which achieved an accuracy of 63% (95% CI=59-67%, AUC=0.62;PLR=0.005,PMLP=0.01,PXGBoost own=0.01) on our data. All models showed improved performance with increasing sample size, with limited improvements aboveN=400. The best model performance was achieved with data-driven feature selection.

Significance

We show that neither the deployment of complex machine learning models nor the assembly of thousands of patients alone is likely to generate significant improvements in our ability to predict post-operative seizure freedom. We instead propose that improved feature selection alongside collaboration, data standardization, and model sharing is required to advance the field.
Prevalence of pesticides in European water and relationship for public health: A protocol for systematic review and meta-analysis
Authors: Valera Manuel Serrano , Vela Nuria , Piuvezam Grasiela , Mateo-Ramírez Francisco , Fernandes Pimenta Isaac Davidson Santiago , Martínez-Alcalá Isabel
Published: February 2023

Background

There is currently a growing interest in the so-called emerging pollutants, such as pesticides, pharmaceuticals, personal hygiene care products, drugs, etc., whose presence in natural ecosystems is not necessarily recent, but the development in latest years of new and more sensitive methods of analysis have allowed their detection. They can be present in the natural environment, in food, and in many products of everyday origin, which suggests that human exposure is massive and universal. These contaminants correspond, in most cases, to unregulated substances, which may be candidates for future regulations, depending on research on their potential health effects and monitoring data regarding their prevalence. Therefore, the study of this type of substances is becoming one of the priority lines of research of the main agencies dedicated to the protection of public and environmental health, such as the World Health Organization (WHO), the United States Environmental Protection Agency (USEPA) or the European Union (EU). In this sense, it is of vital importance to know the nature and quantity of this type of contaminants, to establish preventive mechanisms that minimize their presence in the environment, including, of course, aquatic systems, with special requirements for water human consumption.

Methods

This systematic review and meta-analyzes protocol is conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) statement guidelines and the Cochrane Handbook of Systematic Reviews of Interventions. The papers should include monitoring studies carried out in pesticides polluted waters in Europe. Prevalence studies of emerging contaminants (pesticides) in water resources (watersheds, aquifers, river, marine and springs), waste waters (influent and effluent) and drinking water should be included. Therefore, the comprehensive search strategy will be conducted in the following databases: PubMed, Scopus, Web of Science, EMBASE, ScienceDirect. Two independent reviewers will conduct all study selection procedures, data extraction, and methodological evaluation, and disagreements will be referred to a third reviewer. RevMan 5.3 software will be used to gather data and perform the meta-analysis if possible.

Discussion

This systematic review should provide evidence on the presence of pesticides in European waters in order to establish preventive mechanisms that minimize their presence in the environment.

Dissemination and ethics

The findings of this scoping review will be disseminated in print, at conferences, or via peer-reviewed journals. Ethical approval is not necessary as this paper does not involve patient data.

Systematic review registration

PROSPERO CRD42022348332.
Evolution of horn length and lifting strength in the Japanese rhinoceros beetleTrypoxylus dichotomus
Authors: Weber Jesse N. , Kojima Wataru , Boisseau Romain , Niimi Teruyuki , Morita Shinichi , Shigenobu Shuji , Gotoh Hiroki , Araya Kunio , Lin Chung-Ping , Thomas-Bulle Camille , Allen Cerisse E. , Tong Wenfei , Lavine Laura Corley , Swanson Brook O. , Emlen Douglas J.
Published: February 2023

Rhinoceros beetle (Trypoxylus dichotomus) males have pitchfork-shaped head horns, which they use to pry rival males from the trunks of trees. In the largest males these horns can be three times the length of horns in the two closest sister species. Because this weapon functions as a lever, longer horns should lift with less force than shorter horns (the ‘paradox of the weakening combatant’) unless other elements of the weapon system (e.g., input lever length, muscle mass) evolve to compensate. We used next-generation sequencing approaches to consolidate 23 sample locations into 8 genetically distinguishable populations, reconstructing their historical relationships and providing a comprehensive picture of the evolution of this horn lever system. We show that head horns likely increased in length independently in the Northern and Southern lineages. In both instances this resulted in weaker lifting forces, but this mechanical disadvantage was later ameliorated, to some extent and in some locations, by subsequent reductions to horn length, changes in muscle size, or by an increase in input lever length (head height). Our results reveal an exciting geographic mosaic of differences in weapon size, weapon force, and in the extent and nature of mechanical compensation. Reconstructing the evolution of this weapon system offers critical insights towards meaningfully linking mating system dynamics, selection patterns, and diversity in sexually selected traits.