bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of job-related psychological flexibility, coping style and personality types in depression in Chinese physicians: A cross-section study
Authors: Yao Yongcheng , Jing Xiangzhi , Lu Lingeng
Published: September 2022

To investigate the associations of job-related psychological flexibility, coping style and personality types with and their interactions in depression in Chinese physicians. A cross-sectional survey of 444 physicians was conducted by using the convenience sampling method in the municipal hospitals in Zhengzhou, Henan province. Center for Epidemiological Studies Depression, Work-related Acceptance and Action Questionnaire, the Simplified Coping Style Questionnaire and Eysenck Personality Questionnaire-Revision Short Scale of China were administered to each participant. Depression tendency scores were significantly higher in healthcare workers with intermediate title, age 31 and older, introvert unstable personality than other counterparts, (P < .01). Female and extrovert stable healthcare workers had significantly higher coping score than male and other personality types (P < .05). The scores of job-related psychological flexibility in healthcare workers with Introvert Stable or working in emergency department were significantly higher than their counterparts (P < .01). General linear model algorithm of machine learning showed that Extrovert Unstable was the main risk factor for depression (β = 6.74), followed by Extrovert Stable (β = −4.90), negative coping, positive coping, and length of service. Multivariate regression models showed that a significant interaction existed between coping style, work-related psychological flexibility and Extroversion (β = −0.103, P < .05), independently explaining 0.7% variance of depression, and that a significant interaction existed between coping style, work-related psychological flexibility and neuroticism (β = 0.116, P < .05), independently explaining 1.0% variance of depression. Interactions existed between personality types, coping style and work-related psychological flexibility in depression tendency in Chinese healthcare workers, with neuroticism (extrovert unstable) being a risk factor and extroversion (extrovert stable) being a protective factor. Precision prevention strategies could be made based on personality types to reduce depression in health workers.
Adding colchicine to tocilizumab in hospitalized patients with severe COVID-19 pneumonia: An open-label randomized controlled trial
Authors: Rahhal Alaa , Najim Mostafa , Aljundi Amer Hussein , Mahfouz Ahmed , Alyafei Sumaya Mehdar , Awaisu Ahmed , Habib Mhd, Baraa , Obeidat Ibrahim , Faisal Mohanad Mohammed , Alanzi Meshaal Ali , Nair Arun Prabhakaran , Elhassan Areeg , Al-Dushain Abdullah , Abdelmajid Alaaeldin Abdelmajid , Abdelgader Ahmed Elfadil , Moursi Ahmed Mahmoud Ahmed , Alharafsheh Ahmad Eid Nazzal , Kamar Mohd Ragheb Abou , Goravey Wael , Omar Amr Salah , Abukhattab Mohammed , Khatib Mohamad Yahya , Mohamedali Mohamed Gaafar , AlMaslamani Muna A. Rahman , Alemadi Samar
Published: September 2022

Introduction:

Colchicine acts upstream in the cytokines cascade by inhibiting the nod-like receptor protein 3 (NLRP3) inflammasome while interleukin 6 (IL-6) receptor antagonists, such as tocilizumab, block the end result of the cytokines cascade. Hence, adding colchicine to tocilizumab with the aim of blocking the early and end products of the cytokines cascade, might reduce the risk of developing cytokine storm.

Methods and analysis:

We aim to conduct an open-label randomized controlled trial to evaluate the efficacy and safety of adding colchicine to tocilizumab among patients with severe COVID-19 pneumonia to reduce the rate of invasive mechanical ventilation and mortality. We will include patients with severe COVID-19 pneumonia who received tocilizumab according to our local guidelines. Enrolled patients will be then randomized in 1:1 to colchicine versus no colchicine. Patients will be followed up for 30 days. The primary outcome is the rate of invasive mechanical ventilation and will be determined using Cox proportional hazard model.

Discussion:

Given colchicine’s ease of use, low cost, good safety profile, and having different anti-inflammatory mechanism of action than other IL-6 blockade, colchicine might serve as a potential anti-inflammatory agent among patients with severe COVID-19 pneumonia. This study will provide valuable insights on the use of colchicine in severe COVID-19 when added to IL-6 antagonists.

Ethics and dissemination:

The Medical Research Center and Institutional Review Board at Hamad Medical Corporation in Qatar approved the study protocol (MRC-01-21-299). Results of the analysis will be submitted for publication in a peer-reviewed journal.
Serum neurofilament light chain levels are correlated with the infarct volume in patients with acute ischemic stroke
Authors: Ahn June Woo , Hwang Jaechun , Lee Myunghoon , Kim Jae Hyoung , Cho Hee-Jin , Lee Ho-Won , Eun Mi-Yeon
Published: September 2022

Neurofilament light chains (NfLs) are promising biomarkers of neuroaxonal damage in stroke patients. We investigated the correlations between NfL levels and infarct volume, initial stroke severity, and functional outcomes at discharge in patients with acute ischemic stroke.

We prospectively included 15 patients with first-ever acute ischemic stroke and 8 age- and sex-matched healthy controls without other neurological disorders. Serum NfL levels were measured using the single-molecule array (Simoa) technique twice within 24 hours of admission (NfL1D) and on the seventh hospital day (NfL7D) in patients with stroke and once in healthy controls. We assessed the infarct volume on diffusion-weighted magnetic resonance imaging using the free software ITK-SNAP.

Serum NfL1D levels in stroke patients were significantly higher (28.4 pg/mL; interquartile range [IQR], 43.0) than in healthy controls (14.5 pg/mL; IQR, 3.2; P = .005). Temporal pattern analyses demonstrated that NfL7D levels were increased (114.0 pg/mL; IQR, 109.6) compared to NfL1D levels in all stroke patients (P = .001). There was a strong correlation between NfL7D levels and infarct volume (R = 0.67, P = .007). The difference between NfL1D and NfL7D (NfLdiff levels) was strongly correlated with the infarct volume (R = 0.63; P = .013). However, there was no statistically significant correlation between NfL levels and the initial stroke severity or functional outcomes at discharge.

NfL levels in the subacute stage of stroke and the NfL difference between admission and 7th day of hospital were correlated with infarct volume in patients with acute ischemic stroke.
Citation analysis of the most influential publications on whiplash injury: A STROBE-compliant study
Authors: Ye Shuxi , Chen Qin , Liu Ning , Chen Rongchun , Wu Yaohong
Published: September 2022

Whiplash injury is a common diagnosis and causes substantial economic burden. Numerous papers have been published to provide new insights into whiplash injury. However, so far there has not been a comprehensive analysis of the most influential publications on whiplash injury. This study aimed to determine the 100 most cited publications on whiplash injury and analyze their characteristics. A keyword search was conducted using the Web of Science database. The top 100 cited publications relevant to whiplash injury were gathered. The main characteristics including title, year of publication, citation, authorship, journal, country, institution, and topic were generated. The number of citations of the top 100 cited publications ranged from 82 to 777. Fifteen countries contributed the top 100 publications. Australia had the largest number of publications (26), followed by the United States (21), and Canada (12). The majority of the publications were from Europe (40) and North America (33). A total of 19 institutions and 17 authors published more than one publication. The University of Queensland (16) and the author Sterling M (7) had the leading publication record. This is the first citation analysis to identify and characterize the highest impact researches on whiplash injury. The present analysis provides the most influential studies on whiplash injury, and reveals the leading journals, counties, institutions, and authors with special contributions in this filed. The list may serve as an archive of historical development of whiplash injury and a basis for further research.
Performance of novice intubators in using direct laryngoscope with 3 stylets on a manikin model
Authors: Yang Ting-Hao , Ou Ju-Chi , Chiu Yu-Ju , Tsai Tung-Yao , Mok Sam-I , Ong Jiann Ruey
Published: September 2022

Background:

Tracheal intubation is an important clinical skill for medical students and junior residents (novice intubators). They are usually trained to use a direct laryngoscope (DL) with straight-to-cuff styletted tracheal tubes first. Only later are they exposed to the bougie as an airway adjunct and videolaryngoscope (VL) with either a standard blade or a hyperangulated blade. The purpose of this study was to investigate the performance of novice intubators in using DL with 3 common stylets.

Methods:

We conducted a prospective study to compare the performance of DL with 3 common stylets, namely the straight-to-cuff stylet (S), hyperangulated VL stylet (G), and bougie (B), on a manikin model.

Results:

Among 72 participants, no significant difference was observed between the success rates of S, G, and B at the first attempt (84.72%, 81.94%, and 86.11%, respectively [P = .78]) or within 2 minutes (91.67%, 93.06%, and 91.67%, respectively [P = .94]). For participants with successful intubation within 2 minutes, the average total intubation times for S, G, and B were 25.05, 24.39, and 37.45 seconds, respectively. Among the 3 stylets, B had the longest intubation time, which differed significantly from S and G (P < .01).

Conclusions:

The performances of novice intubators with 3 different stylets were similar. The success rates for DL with either hyperangulated VL stylet or bougie were not inferior compared with the straight-to-cuff stylet on manikin airway training model. If we properly trained novice intubators to use corresponding maneuvers, they can learn to use the 3 stylets early in their airway learning course.
Cytokine-polymorphisms associated with Preeclampsia: A review
Authors: Mora-Palazuelos Carlos , Bermúdez Mercedes , Aguilar-Medina Maribel , Ramos-Payan Rosalío , Ayala-Ham Alfredo , Romero-Quintana Jose Geovanni
Published: September 2022

Background:

Preeclampsia (PE) is a syndromic disorder that affects 2% to 8% of pregnancies and is diagnosed principally when hypertension appears in the second-d half of pregnancy. WHO estimates the incidence of PE to be seven times higher in developing countries than in developed countries. Severe preeclampsia/eclampsia is one of the most important causes of maternal mortality, associated with 50,000 to 100,000 annual deaths globally as well as serious fetal and neonatal morbidity and mortality, especially in developing countries. Even though evidence from family-based studies suggest PE has a heritable component, its etiology, and specific genetic contributions remain unclear. Many studies examining the genetic factors contributing to PE have been conducted, most of them are focused on single nucleotide polymorphisms (SNPs). Given that PE has a very important inflammatory component, is mandatory to examine cytokine-SNPs for elucidating all mechanisms involved in this pathology. In this review, we describe the most important cytokine-polymorphisms associated with the onset and development of PE. We aim to provide current and relevant evidence in this regard.

Methods:

We searched English databases such as PubMed and the National Center for Biotechnology Information. The publication time of the papers was set from the establishment of the databases to February 2022. All studies about Th1/Th2/Th17 cytokines polymorphisms were included in our study.

Results:

SNPs in IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-17A, and IL-22 are associated with the development, early-onset and severity of PE, being the Th1/Th2/Th17 responses affected by the presence of these SNPs.

Conclusions:

The changes in Th1/Th2/Th17 response modify processes such as placentation, control of inflammation, and vascular function. Nonetheless, association studies have shown different results depending on sample size, diagnostic, and population.
TYRO protein tyrosine kinase-binding protein predicts favorable overall survival in osteosarcoma and correlates with antitumor immunity
Authors: Xu Hai-Ru , Chen Jun-Jie , Shen Jin-Ming , Ding Wei-Hang , Chen Jie
Published: September 2022

To explore the prognostic significance and underlying mechanism of TYRO protein tyrosine kinase-binding protein (TYROBP) in osteosarcoma. Firstly, the expression of TYROBP was analyzed using the t test. The Kaplan–Meier plotter analysis and a receiver operating characteristic curve were performed to evaluate the influence of TYROBP on overall survival (OS). Further, Cox regression analysis was conducted to predict the independent prognostic factors for OS of osteosarcoma patients, and a nomogram was constructed. Then, the relationship between TYROBP and clinicopathological characteristics was determined using statistical methods. Enrichment analyses were conducted to evaluate the biological functions of TYROBP. Finally, the ESTIMATE algorithm was used to assess the association of TYROBP with immune cell infiltration. TYROBP was significantly increased in osteosarcoma (all P < .001). However, the high expression of TYROBP was related to better OS in osteosarcoma patients. Cox regression analysis showed that TYROBP was an independent prognostic factor for predicting OS (P = .005), especially in patients of the male sex, age <18 years, metastasis, and tumor site leg/foot (all P < .05). Besides, TYROBP mRNA expression was significantly associated with the tumor site (P < .01) but had no remarkable relationship with age, gender, and metastasis status (all P > .05). Functional annotation and gene set enrichment analysis (GSEA) revealed that TYROBP was mainly involved in immune-related pathways. Importantly, TYROBP positively correlated with immune scores (P < .001, R = .87). TYROBP served as an independent prognostic biomarker for OS in osteosarcoma. High TYROBP expression might prolong the survival of osteosarcoma patients mainly through promoting antitumor immunity.
Single incision laparoscopic totally preperitoneal hernioplasty (SIL-TPP): Lessons learned from 102 procedures and initial experience
Authors: Zhou Encheng , Qi Changlei , Wang Xiaojun , Fei Ting , Huang Qing
Published: September 2022

Background:

The abdominal wall in groin area is conventionally considered that it was comprised by 9 layers. Single incision laparoscopy totally extraperitoneal hernioplasty (SIL-TEP) reported before were operated through the front of the posterior rectus sheath.

Method:

102 SIL-TPP were conducted from October 2018 to October 2020 at The Affiliated Hospital of Medical School of Ningbo University using a self-made single-port device and standard laparoscopic instruments. Clinical data, demographic and intraoperative findings, and short-term postoperative outcomes were analyzed.

Results:

Of the 102 hernias treated, 46 were right inguinal hernias, 33 were left inguinal hernias and 23 were double-side inguinal hernias. All patients received the SIL-TPP and no conversion happened. The mean left-side and right-side hernia operative time was almost same. The left-side and right-side operative time were 75.48 ± 26.95 and 76.24 ± 26.09 minutes, respectively. The mean operative time was 75.92 ± 26.45 (range, 29–170 minutes) in unilateral inguinal hernia. Mean operative time was 104.17 ± 28.58 minutes (range, 67–180 minutes) in double-side inguinal hernia. The intraoperative complications rate was 21.57 (22/102) and all the complications were Peritoneum or sac tearing. Postoperative complications occurred in 3 cases (1 case wound seroma, 1 case urinary retension and 1 case upper respiratory infection) and were successfully treated conservatively. The mean hospital stay was 2.8646 ± 1.38 days. The 24 hours Visual analogue scale score was 2.28 ± 0.77. During follow-up to June 2022, no recurrence case occurred.

Conclusion:

SIL-TPP is safe and feasible. SIL-TPP has its unique skills and advantages to treat inguinal hernia. Large-scale randomized controlled trials comparing SIL-TPP inguinal hernia repair with conventional single port and conventional three port laparoscopic totally extraperitoneal hernioplasty with short-term outcome and long-term recurrence rate are needed to confirm these results.
Levetiracetam poisoning with acute kidney injury treated with hemodialysis: A case report
Authors: Sedogawa Hiraku , Watanabe Norihiro , Hirose Yoshikazu , Mizouchi Naoko , Shimagaki Shunri , Yamaguchi Hiroki , Hirose Yasuo
Published: September 2022

Introduction:

Levetiracetam is a newer second-generation anticonvulsant for the treatment of generalized and partial seizure disorders. Common adverse effects are rhabdomyolysis and neuropsychiatric problems, such as somnolence, dizziness, and mood changes. The present report describes the first case, to our knowledge, of levetiracetam overdose resulting in acute kidney injury for which hemodialysis was required.

Patient concerns:

A 51-year-old man presented with hypotension and disturbance of consciousness with subsequent development of oliguria and elevated creatinine. Based on his history of ingesting a large dose of levetiracetam and the course of the disease, he was considered to have been poisoned by levetiracetam.

Diagnosis:

Acute kidney injury induced by levetiracetam poisoning.

Interventions/Outcomes:

Dialysis was performed for the rapidly progressing renal failure. His renal function improved, and he was weaned from dialysis and discharged home on the 19th day.

Conclusion:

We should be aware of the possibility that severe renal function deterioration may occur in some patients with levetiracetam overdose. It is possible that clinicians underestimate the occurrence of this problem. In cases of acute renal failure in levetiracetam poisoning, induction of dialysis is beneficial.
A systematic review of prognosis of ABO blood group and rhesus factor on outcomes in patients with bladder cancer
Authors: Yang Haiming , Yan Jingxin
Published: September 2022

Background:

Bladder cancer (BC) is the 10th most common malignancy worldwide, and some studies reported that ABO blood type or/and rhesus factor has been identified as a prognostic oncologic marker for patients with BC. We carried out a systematic review to assess the prognosis of ABO blood group and rhesus factor on outcomes in patients with bladder cancer.

Methods:

We searched databases through February 2022 for studies assessing blood group on outcomes in patients with bladder cancer.

Results:

We included ten studies with 15,204 participants. We found that blood type A is relevant to non-muscle-invasive BC patients treated with transurethral resection of bladder tumor and blood type B patients have a lower incidence of disease recurrence and progression. Blood type O and non-O blood type have not been found to be related to disease recurrence. However, in multivariable analyses, blood type O and non-O blood type are associated with cancer-specific mortality (CSM). Other than that, blood type B doesn’t have statistical significance for BC patients accepted radical cystectomy (RC). The same results showed in blood type AB non-muscle-invasive bladder cancer patients treated with RC.

Conclusions:

Our study confirmed that a particular association of blood type for prognosis of patients with BC, and ABO blood group antigen expression can be suitable biomarkers for BC. We also found that rhesus factor has no impact on prognosis of BC patients.
Qigong for mental health and sleep quality in postmenopausal women: A randomized controlled trial
Authors: Carcelén-Fraile María del Carmen , Aibar-Almazán Agustín , Martínez-Amat Antonio , Jiménez-García José Daniel , Brandão-Loureiro Vânia , García-Garro Patricia Alexandra , Fábrega-Cuadros Raquel , Rivas-Campo Yulieth , Hita-Contreras Fidel
Published: September 2022

Background:

Menopause is one of the stages in a woman’s life that affects her psychological health, the most frequent being anxiety and depression. In addition, another problem related to this stage is the lack of sleep that causes a decrease in the quality of sleep. The purpose of this randomized controlled trial was to analyze the effectiveness of a Qigong exercise program on sleep quality, anxiety, and depression in Spanish postmenopausal women.

Methods:

A total of 125 women were randomly assigned to an experimental group (EG) (n = 63) that carried out a Qigong exercise program for 12 weeks, or a control group (CG) (n = 62), which did not perform any type of intervention. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and anxiety and depression using the Hospital Anxiety and Depression Scale (HADS).

Results:

Women who underwent an intervention program experienced significant improvements for all measured variables, except for the use of sleeping medication and daytime dysfunctions that did not show any significant effect with respect to the group and group × time interaction.

Conclusions:

After an intervention based on a BaDuanJin Qigong exercise program for 12 weeks, improvements were observed in sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbances, the total score of the PSQI, anxiety and depression in postmenopausal Spanish women.
Association of follicle stimulating hormone and serum lipid profiles in postmenopausal women
Authors: Xu Zhengfen , Gu Shuiqin , Wu Xiaojie , Zhou Ying , Li Huan , Tang Xuedong
Published: September 2022

The aim of the study was to observe the association between follicle stimulating hormone (FSH) levels and serum lipid profiles in postmenopausal women. A total of 411 healthy postmenopausal women with a mean age of 55 years (range 45–65 years) were enrolled in this study. Data on age, time of last menstrual period, past medical history, use of medications, and smoking status were collected, and body weight, height, and blood pressure were measured. Blood samples were collected to measure the serum concentrations of FSH, luteinizing hormone (LH), estradiol (E2), glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) using routine methods. FSH levels were negatively associated with LDL-C, even after adjustment for age, LH, E2, BMI, systolic blood pressure (SBP), and diastolic blood pressure (DBP) (OR = 0.185, 95% CI = 0.051‐0.669). Although FSH may also be negatively associated with dyslipidemia (P = .06 for trend) and hypercholesterolemia (P = .079 for trend), but no statistical significance was found after adjusting for confounding factors, particularly BMI. All relevant data are within the paper and its Supporting Information files. The results indicated that lower FSH levels might increase the odds of dyslipidemia, especially the risk of LDL-C elevation, which is an important factor that increases the risk of CVD in postmenopausal women.
Advantages of an alternate-day glucocorticoid treatment strategy for the treatment of IgG4-related disease: A preliminary retrospective cohort study
Authors: Fukui Sho , Nakai Takehiro , Kawaai Satoshi , Ikeda Yukihiko , Suda Masei , Nomura Atsushi , Tamaki Hiromichi , Kishimoto Mitsumasa , Ohde Sachiko , Okada Masato
Published: September 2022

Alternate-day glucocorticoid (GC) therapy is a treatment option that can reduce GC-associated adverse events. We investigated the safety and efficacy of alternate-day GC therapy in patients with immunoglobulin G4-related disease (IgG4-RD).

Medical records of patients with IgG4-RD who were followed for at least one year at St. Luke’s International Hospital, Tokyo, Japan, from 2004 to 2020 were reviewed. Patients who fulfilled comprehensive IgG4-RD diagnostic criteria were divided into alternate-day or daily GC treatment groups based on their treatment protocol. The effect of alternate-day GC therapy on glucocorticoid toxicity index (GTI) score was evaluated using multilinear analysis with adjustments for cumulative GC doses until each assessment point and propensity scores (PS) for alternate-day GC therapy. Kaplan–Meier curves and Cox proportional hazard models were used to assess the efficacy of alternate-day GC therapy for disease control.

Among the 67 patients with IgG4-RD, patients with alternate-day (n = 13) and daily (n = 31) GC treatments were analyzed after excluding 23 ineligible patients. The median (interquartile range) age was 64 (60–70) years, 29 (65.9%) were male patients, 26 (59.1%) patients had positive biopsy results, and the median follow-up period was 1643 days. Significantly more patients with alternate-day GC treatment used concomitant immunosuppressants (11 [84.6%] vs 11 [35.5%]; P = .007). The alternate-day strategy significantly lowered the GTI score after adjusting for cumulative GC dose until the assessment and PS (adjusted coefficient: −29.5 [−54.3, −4.8], P = .021 at 12 months; −20.0 [−39.8, −0.1], P = .049 at 24 months). Serious infections were numerically less frequent in the alternate-day group (incidence ratio [95% confidence interval [CI]: 0.45 [0.05, 3.63], P = .45). Most patients (92.3%) in the alternate-day GC treatment group and all patients in the daily GC treatment group showed treatment responses in the remission induction therapy. The PS-adjusted hazard ratio of alternate-day GC treatment for disease flares was not significant (1.55 [0.53, 4.51]; P = .43).

The alternate-day treatment strategy significantly reduced GC-related adverse events regardless of the cumulative GC dose. Alternate-day GC treatment is a feasible option for patients with IgG4-RD, without a significant increase in disease flares particularly when combined with immunosuppressants.
Cutoff values of protein induced by vitamin K absence or antagonist II for diagnosing hepatocellular carcinoma
Authors: Jang Tyng-Yuan , Dai Chia-Yen
Published: September 2022

Protein induced by vitamin K absence or antagonist II (PIVKA-II) is a promising serum marker for hepatocellular carcinoma (HCC). There are limited data on its cutoff value in HCC for Taiwanese cirrhosis patients. This study aimed to investigate the diagnostic value of PIVKA-II levels in patients with suspected HCC. In total, 88 patients with chronic hepatitis and suspected HCC by ultrasound, elevated α-fetoprotein (AFP) or PIVKA-II levels were consecutively enrolled. Their baseline characteristics and findings on dynamic phases of computed tomography (CT) or magnetic resonance imaging (MRI) were examined. Sixty participants had cirrhosis and 34 had HCC. The median levels of PIVKA-II in non-cirrhosis and cirrhosis patients without or with HCC were 28.0, 48.0, and 847.0 mAU/mL, respectively. The optimal cutoff value of PIVKA-II in predicting HCC was 78.0 mAU/mL. Combining AFP with PIVKAII mildly increased its diagnostic performance for HCC, yielding higher specificity and positive predictive value. Significant factors predicting HCC in multivariate regression analysis were PIVKA >78.0 mAU/mL and fatty liver. Monitoring PIVKA-II level is suitable for noninvasively assessing HCC in patients with chronic hepatitis, particularly with AFP.
Mortality Risk in Pediatric Sepsis Based on C-reactive Protein and Ferritin Levels
Authors: Horvat Christopher M. , Fabio Anthony , Nagin Daniel S. , Banks Russell K. , Qin Yidi , Park Hyun-Jung , Kernan Kate F. , Canna Scott W. , Berg Robert A. , Wessel David , Pollack Murray M. , Meert Kathleen , Hall Mark , Newth Christopher , Lin John C. , Doctor Allan , Shanley Tom , Cornell Tim , Harrison Rick E. , Zuppa Athena F. , Reeder Ron W. , Sward Kathy , Holubkov Richard , Notterman Daniel A. , Dean J. Michael , Carcillo Joseph A. ,   on behalf of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network
Published: September 2022

OBJECTIVES:

Interest in using bedside C-reactive protein (CRP) and ferritin levels to identify patients with hyperinflammatory sepsis who might benefit from anti-inflammatory therapies has piqued with the COVID-19 pandemic experience. Our first objective was to identify patterns in CRP and ferritin trajectory among critically ill pediatric sepsis patients. We then examined the association between these different groups of patients in their inflammatory cytokine responses, systemic inflammation, and mortality risks.

DATA SOURCES:

A prospective, observational cohort study.

STUDY SELECTION:

Children with sepsis and organ failure in nine pediatric intensive care units in the United States.

DATA EXTRACTION:

Two hundred and fifty-five children were enrolled. Five distinct clinical multi-trajectory groups were identified. Plasma CRP (mg/dL), ferritin (ng/mL), and 31 cytokine levels were measured at two timepoints during sepsis (median Day 2 and Day 5). Group-based multi-trajectory models (GBMTM) identified groups of children with distinct patterns of CRP and ferritin.

DATA SYNTHESIS:

Group 1 had normal CRP and ferritin levels (n = 8; 0% mortality); Group 2 had high CRP levels that became normal, with normal ferritin levels throughout (n = 80; 5% mortality); Group 3 had high ferritin levels alone (n = 16; 6% mortality); Group 4 had very high CRP levels, and high ferritin levels (n = 121; 11% mortality); and Group 5 had very high CRP and very high ferritin levels (n = 30; 40% mortality). Cytokine responses differed across the five groups, with ferritin levels correlated with macrophage inflammatory protein 1α levels and CRP levels reflective of many cytokines.

CONCLUSIONS:

Bedside CRP and ferritin levels can be used together to distinguish groups of children with sepsis who have different systemic inflammation cytokine responses and mortality risks. These data suggest future potential value in personalized clinical trials with specific targets for anti-inflammatory therapies.
An Unusual Case of Infantile Hepatic Steatosis Caused by Coconut-Based Infant Formula
Authors: Prieto Jimenez Paula M. , Jun-Ihn Esther , Matthews Michael , Lollie Trang , Qu Yong , Martin Martin G.
Published: September 2022

We report a 5-month-old African American male with hepatic steatosis secondary to chronic and exclusive homemade coconut milk formula ingestion. Findings resolved with discontinuation.
Structural characterisation of methanogen pseudomurein cell wall peptide ligases homologous to bacterial MurE/F murein peptide ligases
Authors: Subedi Bishwa P. , Schofield Linley R. , Carbone Vincenzo , Wolf Maximilian , Martin William F. , Ronimus Ron S. , Sutherland-Smith Andrew J.
Published: September 2022

Archaea have diverse cell wall types, yet none are identical to bacterial peptidoglycan (murein). Methanogens

Methanobacteria

and

Methanopyrus

possess cell walls of pseudomurein, a structural analogue of murein. Pseudomurein differs from murein in containing the unique archaeal sugar N-acetyltalosaminuronic acid instead of N-acetylmuramic acid, β−1,3 glycosidic bonds in place of β−1,4 bonds and only l-amino acids in the peptide cross-links. We have determined crystal structures of methanogen pseudomurein peptide ligases (termed pMurE) from

Methanothermus fervidus

(Mfer762) and

Methanothermobacter thermautotrophicus

(Mth734) that are structurally most closely related to bacterial MurE peptide ligases. The homology of the archaeal pMurE and bacterial MurE enzymes is clear both in the overall structure and at the level of each of the three domains. In addition, we identified two UDP-binding sites in Mfer762 pMurE, one at the exterior surface of the interface of the N-terminal and middle domains, and a second site at an inner surface continuous with the highly conserved interface of the three domains. Residues involved in ATP binding in MurE are conserved in pMurE, suggesting that a similar ATP-binding pocket is present at the interface of the middle and the C-terminal domains of pMurE. The presence of pMurE ligases in members of the Methanobacteriales and Methanopyrales, that are structurally related to bacterial MurE ligases, supports the idea that the biosynthetic origins of archaeal pseudomurein and bacterial peptidoglycan cell walls are evolutionarily related.
Neuroscience-Informed Classification of Prevention Interventions in Substance Use Disorders: An RDoC-based Approach
Authors: Rezapour Tara , Rafei Parnian , Baldacchino Alex , Conrod Patricia J. , Dom Geert , Fishbein Diana H. , Kazemi Atefeh , Hendriks Vincent , Newton Nicola , Riggs Nathaniel R. , Squeglia Lindsay M. , Teesson Maree , Vassileva Jasmin , Verdejo-Garcia Antonio , Ekhtiari Hamed
Published: September 2022

Neuroscience has contributed to uncover the mechanisms underpinning substance use disorders (SUD). The next frontier is to leverage these mechanisms as active targets to create more effective interventions for SUD treatment and prevention. Recent large-scale cohort studies from early childhood are generating multiple levels of neuroscience-based information with the potential to inform the development and refinement of future preventive strategies. However, there are still no available well-recognized frameworks to guide the integration of these multi-level datasets into prevention interventions. The Research Domain Criteria (RDoC) provides a neuroscience-based multi-system framework that is well suited to facilitate translation of neurobiological mechanisms into behavioral domains amenable to preventative interventions. We propose a novel RDoC-based framework for prevention science and adapted the framework for the existing preventive interventions. From a systematic review of randomized controlled trials using a person-centered drug/alcohol preventive approach for adolescents, we identified 22 unique preventive interventions. By teasing apart these 22 interventions into the RDoC domains, we proposed distinct neurocognitive trajectories which have been recognized as precursors or risk factors for SUDs, to be targeted, engaged and modified for effective addiction prevention.
“They assume by having sex, they are a husband”: How Indian Female Sex Workers navigate relationship fluidity and sexual risk
Authors: Panchanadeswaran Subadra , Chacko Shubha , Hwahng Sel , Rahill Guitele , Joshi Manisha , Manasi Ardra
Published: September 2022

There is limited evidence that highlights female sex workers’ (FSWs) agency in negotiating HIV risk in the context of multiple sexual relationships. Using a Gendered Vulnerability framework, this study employed a phenomenological approach to explore the FSWs’ active navigation of concurrent sexual relationships and their perceptions and assessments of HIV risk and sexual negotiation. Sixty (60) FSWs participated in the study. Data were collected through semi-structured interviews and focus group discussions. ATLAS.ti provided an interpretive framework for data analysis. Findings revealed that FSWs navigate a complex landscape of multiple sexual relationships that influenced their condom use decisions. Despite possessing accurate HIV knowledge, FSWs in this study indicated that multiple circumstances (e.g., economic constraints, damaging gender norms, merely paying transactional relationships with some clients, emotional attachments with others, gender-role bound relationships, and instances of sexual victimization) influenced their perceptions of power and their desires and perceived capacities for HIV risk and prevention decisions. A nuanced understanding of FSWs’ concurrent fluid relationships and the cultural contexts in which Indian FSWs work are vital when planning programs and policies for HIV prevention.
Load and fatigue monitoring in instrumental musicians using an online app: A Pilot Study
Authors: McCrary J. Matt , Ascenso Sara , Savvidou Paola , Schraft Séverine , McAllister Lesley , Redding Emma , Bastepe-Gray Serap , Altenmüller Eckart
Published: September 2022

Background/Aims

High occupational injury rates are reported in musicians, with a career prevalence of up to 89%. Fatigue and playing (over)load are identified as key risk factors for musicians’ injuries. Self-report fatigue management strategies in sport have demonstrated preventive effects. A self-report fatigue management tool for musicians was developed based on a Delphi survey of international experts and hosted in an online app. The aims of this study are to evaluate the content validity and uptake of this new tool, and explore associations between collected performance quality, physical/psychological stress, pain, injury and fatigue data.

Methods

University and professional musicians were asked to provide entries into the online app twice per week for one to six months. Entries into the app were designed to take 2-3 minutes to complete and consisted of the following: 6 questions regarding playing load over the previous 72 hours; 5 questions regarding current levels in key physical/psychological stress domains (sleep, recovery, overplaying, pain, fitness); one question self-rating of performance quality over the previous day; one question regarding current musculoskeletal symptoms; a reaction time task to evaluate psychomotor fatigue.

Results

N=96 participants provided an average of 2 app entries (range 0 – 43). Increased playing time, rating of perceived exertion (RPE), and feelings of having to ‘play too much’ were consistently associated with increased self-rated performance quality (p≤ .004; 6.7<|t|<2148.5). Increased ratings of feeling fit and recovering well were consistently associated with reduced pain severity (p<.001; 3.8<|t|<20.4). Pain severity was increased (6.5/10 vs. 2.5/10; p<.001) in participants reporting playing-related musculoskeletal disorders (PRMDs; symptoms affecting playing).

Conclusion

The prospective value of regular individual self-report playing load, stress, and performance data collection in musicians is clear. However, limited uptake of the online fatigue management app piloted in this study indicates that new approaches to the collection of these data are needed to realize their potential impact.
Value-Based Neural Representations Predict Social Decision Preferences
Authors: Guassi Moreira João F. , Méndez Leal Adriana S. , Waizman Yael H. , Tashjian Sarah M. , Galván Adriana , Silvers Jennifer A.
Published: September 2022

Social decision-making is omnipresent in everyday life, carrying the potential for both positive and negative consequences for the decision-maker and those closest to them. While evidence suggests that decision makers use value-based heuristics to guide choice behavior, very little is known about how decision makers’ representations of other agents influence social choice behavior. We used multivariate pattern expression analyses on fMRI data to understand how value-based processes shape neural representations of those affected by one’s social decisions and whether value-based encoding is associated with social decision preferences. We found that stronger value-based encoding of a given close other (e.g., parent) relative to a second close other (e.g., friend) was associated with a greater propensity to favor the former during subsequent social decision-making. These results are the first to our knowledge to explicitly show that value-based processes affect decision behavior via representations of close others.
Wildflower phenological escape differs by continent and spring temperature
Authors: Lee Benjamin R. , Miller Tara K. , Rosche Christoph , Yang Yong , Heberling J. Mason , Kuebbing Sara E. , Primack Richard B.
Published: September 2022

Temperate understory plant species are at risk from climate change and anthropogenic threats that include increased deer herbivory, habitat loss, pollinator declines and mismatch, and nutrient pollution. Recent work suggests that spring ephemeral wildflowers may be at additional risk due to phenological mismatch with deciduous canopy trees. The study of this dynamic, commonly referred to as “phenological escape”, and its sensitivity to spring temperature is limited to eastern North America. Here, we use herbarium specimens to show that phenological sensitivity to spring temperature is remarkably conserved for understory wildflowers across North America, Europe, and Asia, but that canopy trees in North America are significantly more sensitive to spring temperature compared to in Asia and Europe. We predict that advancing tree phenology will lead to decreasing spring light windows in North America while spring light windows will be maintained or even increase in Asia and Europe in response to projected climate warming.
Small Molecule Protein Assembly Modulators with Pan-Cancer Therapeutic Efficacy
Authors: Lingappa Anuradha F. , Akintunde Olayemi , Ewald Connie , Froehlich Markus , Ziari Niloufar , Michon Maya , Yu Shao Feng , Mallesh Suguna , Lin Jim , Kitaygorodskyy Anatoliy , Solas Dennis , Reed Jonathan C. , Lingappa Jaisri R. , Mueller-Schiffmann Andreas , Korth Carsten , Prasad Dharma , Nalca Aysegul , Aston Emily , Fabbri Brad , Anand Sanjeev , Campi Thomas W. , Petrouski Emma , Dey Debendranath , Andrews David W. , Lingappa Vishwanath R.
Published: September 2022

Two structurally-unrelated small molecule chemotypes, represented by compounds PAV-617 and PAV-951 with antiviral activity in cell culture against monkeypox virus (MPXV) and human immunodeficiency virus (HIV) respectively, were studied for anti-cancer efficacy. Each exhibited apparent pan-cancer cytotoxicity, reasonable pharmacokinetics, and non-toxicity in mice at active concentrations. Anti-tumor properties of both chemotypes, were validated in mouse xenografts against A549 human lung cancer and, for one of the chemotypes, against HT-29 colorectal cancer. The targets of these compounds are unconventional: each binds to a different transient, energy-dependent multi-protein complex containing the protein TRIM28/KAP1, an allosteric modulator known to regulate mechanisms underlying viral and nonviral disease states including cancer. Treatment with these compounds alters the target multi-protein complexes in a manner consistent with allosteric modulation as their mechanism of action. These compounds appear to remove a block, crucial for cancer survival and progression, on the homeostatic linkage of uncontrolled cellular proliferation to apoptosis. These compounds provide starting points for development of next-generation non-toxic, pan-cancer therapeutics.
The contribution of mutation to variation in temperature-dependent sprint speed in zebrafish,Danio rerio
Authors: Miller Christina L. , Sun Derek , Thornton Lauren H. , McGuigan Katrina
Published: September 2022

The contribution of new mutations to phenotypic variation, and the consequences of this variation for individual fitness, are fundamental concepts for understanding genetic variation and adaptation. Here, we investigated how mutation influenced variation in a complex trait in zebrafish,Danio rerio. Typical of many ecologically relevant traits in ectotherms, swimming speed in fish is temperature-dependent, with evidence of adaptive evolution of thermal performance. We chemically induced novel germline point mutations in males, and measured sprint speed in their sons at six temperatures (between 16°C and 34°C). Mutational effects on speed were strongly positively correlated among temperatures, resulting in statistical support for only a single axis of mutational variation, reflecting temperature-independent variation in speed (faster-slower mode). While these results suggest pleiotropic effects on speed across different temperatures, when mutation have consistent directional effects on each trait, spurious correlations arise via linkage, or heterogeneity in mutation number. However, mutation did not change mean speed, indicating no directional bias in mutational effects. The results contribute to emerging evidence that mutations may predominantly have synergistic cross-environment effects, in contrast to conditionally neutral or antagonistic effects which underpin thermal adaptation. However, aspects of experimental design might limit resolution of mutations with non-synergistic effects.
Study of the associations between short telomeres, sex hormones and pulmonary fibrosis
Authors: Duckworth Anna , Ruth Katherine S. , Prague Julia K. , Russell Anne-Marie , Almond Howard , Conway John , Beaumont Robin N , Wood Andrew R , Martin Susan , Lunnon Katie , Lindsay Mark A. , Murray Anna , Gibbons Michael A. , Tyrrell Jess , Scotton Chris J.
Published: September 2022

Background

Pulmonary fibrosis (PF) is an incurable fibrotic lung disease with limited treatment options and a high mortality. Evidence is growing that short telomeres cause both heritable and idiopathic pulmonary fibrosis (IPF). Based on survival data, we hypothesised that sex hormones are protective against premature telomere attrition and could influence PF disease onset and/or progression.

Methods

Associations between IPF, sex hormone concentrations and measured leukocyte telomere length (LTL) were examined for unrelated UK Biobank participants of European ancestry with a diagnosis of IPF (415 females, 718 males) against controls (204,321 females, 174,254 males). Polygenic risk scores were used to explore causality between sex hormone indices, LTL and disease.

Findings

Strong associations were found between IPF and LTL. For females, higher odds of having IPF was associated with early menopause and premature ovarian failure. Menopause age correlated positively with both age of IPF diagnosis and age of death. For males, IPF prevalence and stages of disease were associated with serum bioavailable testosterone concentrations. For both sexes, evidence of lower concentrations of sex hormones was associated with shorter LTL. Genetic analysis also inferred bi-directional causal links between sex hormone binding globulin concentration, which impacts free testosterone concentration, and LTL in males.

Interpretation

Our findings suggest that higher sex hormone concentrations protect against IPF onset and progression, possibly by slowing telomere shortening. Hormonal supplementation may delay or prevent disease onset for those with telomere-associated PF risk and improve disease prognosis. This warrants further exploration in a randomised controlled trial.

Funding

Medical Research Council.
Breast cancer in pregnant young women: clinicohistological profile, risk of death and pregnancy outcomes
Authors: Nicolás Ramírez-Torres , Rodolfo Rivas-Ruíz , Alfonso Reyes-López , Kingston Ureña-Wong
Published: September 2022

Objective

To describe a set of tumor characteristics, prognosis and course of pregnancy in patients diagnosed with pregnancy-associated breast cancer (PABC).

Methods

Retrospective cohort study of PABC young women. The histological profile, survival and pregnancy outcomes were assessed. Nonparametric tests, Fisher’s exact test, Kaplan-Meier method, Cox regression and multivariate logistic regression were used for statistical analyses.

Results

We assessed 16 PABC patients. All women self-palpated a breast mass, the women ≤ 35 years of age were diagnosed with unfavorable characteristics: advanced stage (88.8%), positive clinically lymph nodes (100%), high grade (55.5%), ER-negative (77.8%) and high-risk Nottingham prognostic index (66.7%).

Seven deaths were observed with a median follow-up for overall survival (OS) of 64.5 months (range: 15-90). The 5-year OS rates were worse for patients with pathological lymph nodes > 4 (25%; p = 0.001) and with ER-negative disease (50%; p = 0.646).

In our multivariate analysis, the nodal involvement was the only predictor associated to a worse OS (hazard ratio = 1.4, 90% confidence interval [CI]: 1.14 to 1.8). The following risk factors could influence in the risk of a preterm birth: mother’s older age, gestational age at diagnosis and the chemotherapy during pregnancy, but their adjusted ORs of .61 (90% CI: 0.34 to 1), .80 (90% CI: 0.66 to 0.9) and .01 (90% CI: 0.00 to 0.9), respectively did not support statistically such an effect. Most cases of cases (77.7%) exposed to chemotherapy during pregnancy got a live term birth.

Conclusion

Our findings described a more aggressive histological profile for youngest pregnant women coupled the delayed diagnosis might explain the high-risk of death. Simultaneous management of breast cancer and pregnancy was feasible.