bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Chemotherapy Timing in Pregnancy With Congenital Malformation
Authors: van Gerwen Mathilde , Maggen Charlotte , Cardonick Elyce , Verwaaijen Emma J. , van den Heuvel-Eibrink Marry , Shmakov Roman G. , Boere Ingrid , Gziri Mina M. , Ottevanger Petronella B. , Lok Christianne A. R. , Halaska Michael , Shao Long Ting , Struys Ilana , van Dijk-Lokkart Elisabeth M. , Van Calsteren Kristel , Fruscio Robert , Zola Paolo , Scarfone Giovanna , Amant Frédéric 
Published: December 2021

(Abstracted from JAMA Network Open 2021;4:e2113180)
Chemotherapy puts a developing fetus at risk of teratogenic effects. The standard recommendation is that chemotherapy be administered after organogenesis is complete, however, the exact gestational age that chemotherapy can be administered safely and avoid causing congenital malformations remains unknown.
Human Metapneumovirus Infection in a Children’s Hospital – It Should Get More Attention
Authors: Hani Nellie , Gornick Wendi , Huff Beth , Atienza Jamie , Singh Jasjit 
Published: December 2021

Background:
Respiratory syncytial virus (RSV) and influenza infections are a major cause of hospitalization and intensive care unit (ICU) admission to children’s hospitals and are closely tracked. We compared data over 6 seasons of human metapneumovirus (hMPV), RSV and influenza infections.

Methods:
During the 2014–2019 winter viral seasons, hMPV, RSV and influenza infections were tracked. For hMPV admissions, rates of hospitalizations, ICU admissions, hospital-acquired infections (HAIs) and mortalities were assessed and compared with RSV and influenza admissions. Retrospective data was used to study patients infected with hMPV.

Results:
During the winter seasons of 2014–2019, the rates of hospitalization due to hMPV were significantly higher than both RSV and influenza. ICU admissions, deaths and HAIs for hMPV were similar to RSV and influenza.
Of the 471 total cases with hMPV, 58 (12.3%) had chronic lung disease (CLD) and 23 (4.9%) were tracheostomy dependent. Among 104 hMPV ICU admissions from 2013 to 2019, 86 (82%) had an underlying medical diagnosis, 30 (29%) had CLD, 21 (20%) had tracheostomies and 33 (32%) required mechanical ventilation. The average age of hMPV infected children in our ICU is 3 years and 10 months.

Conclusions:
Our large descriptive study of hMPV infected children over 6 seasons showed higher rates of hospitalization compared with RSV and influenza, similar ICU and HAI rates, and deaths. ICU admitted children often had associated co-morbidities, including CLD. Further studies for focused disease surveillance and potential vaccine development for high-risk children are needed.
Characterizing Pain Leading to Emergency Medical Services Activation in Heart Failure
Authors: Smith Asa B. , Jung Miyeon , Lee Christopher , Pressler Susan J. 
Published: December 2021

Background
Pain is a common but understudied symptom among patients with heart failure (HF) transported by emergency medical services (EMS). The aims were to determine explanatory factors of a primary complaint of pain and pain severity, and characterize pain among patients with HF transported by EMS.

Methods
Data from electronic health records of patients with HF transported by EMS within a midwestern United States county from 2009 to 2017 were analyzed. Descriptive statistics, χ2, analysis of variance, and logistic and multiple linear regression analyses were used.

Results
The sample (N = 4663) was predominantly women (58.1%) with self-reported race as Black (57.7%). The mean age was 64.2 ± 14.3 years. Pain was the primary complaint in 22.2% of the sample, with an average pain score of 6.8 ± 3.1 out of 10. The most common pain complaint was chest pain (68.1%). Factors associated with a primary pain complaint were younger age (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.96–0.97), history of myocardial infarction (OR, 1.96; 95% CI, 1.55–2.49), and absence of shortness of breath (OR, 0.67; 95% CI, 0.58–0.77). Factors associated with higher pain severity were younger age (b = −0.05, SE = 0.013), being a woman (b = 1.17, SE = 0.357), and White race (b = −1.11, SE = 0.349).

Conclusions
Clinical and demographic factors need consideration in understanding pain in HF during EMS transport. Additional research is needed to examine these factors to improve pain management and reduce transports due to pain.
Effect of Dietary Sodium Restriction on the Quality of Life of Patients With Heart Failure
Authors: Zhu Chenya , Cheng Ming , Su Yue , Ma Tianyu , Lei Xiaoqing , Hou Yunying 
Published: December 2021

Background
Dietary salt restriction is recommended by many guidelines for patients with heart failure (HF). Quality of life (QoL) is an important end point of this intervention. However, the literature is still limited regarding the effect of dietary salt restriction on QoL in patients with HF.

Aims
We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the effect of dietary sodium restriction on QoL in patients with HF.

Methods
We searched PubMed (MEDLINE), the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, and Cumulative Index to Nursing and Allied Health from the establishment of each database to December 20, 2020. We included randomized controlled trials with sodium restriction as an intervention. The primary outcome was QoL, and the secondary outcomes were mortality, readmission, and fatigue. We obtained the full text of potentially relevant trials, extracted data from the included trials, assessed their risk of bias, and performed a meta-analysis.

Results
We included 10 trials (1011 participants with HF) with 7 days to 83 months of follow-up. Dietary sodium restriction did not improve QoL over the long term (>30 days) (P = .61). The pooled effects showed that this intervention might increase mortality risk (P < .00001). It did not reduce the readmission rate within the short term (≤30 days) (P = .78) but increased the readmission rate over the long term (P = .0003).

Conclusion
Our study did not show that interventions to restrict dietary sodium had a positive effect on patients with HF in terms of QoL, mortality, or readmission.
Brief Report: Undertreated Midlife Symptoms for Women Living With HIV Linked to Lack of Menopause Discussions With Care Providers
Authors: King Elizabeth M. , Kaida Angela , Mayer Ulrike , Albert Arianne , Gormley Rebecca , de Pokomandy Alexandra , Nicholson Valerie , Cardinal Claudette , Islam Shaz , Loutfy Mona , Murray Melanie C. M. 
Published: December 2021

Background:
Increasingly, women living with HIV are entering menopause (ie, cessation of menses for ≥1 year) and experiencing midlife symptoms. Menopausal hormone therapy (MHT) is first-line therapy for bothersome hot flashes and early menopause (ie, before age 45 years); however, its use in women living with HIV is poorly described. We conducted a cross-sectional assessment of MHT uptake and barriers to use in this group.

Setting:
This study was conducted across 3 Canadian provinces from 2015 to 2017.

Methods:
Perimenopausal and postmenopausal women living with HIV (35 years or older) in the Canadian HIV Women's Sexual and Reproductive Health Cohort Study who answered questions related to MHT use were included. Univariable/multivariable logistic regression evaluated factors associated with MHT use, adjusted for age and contraindications.

Results:
Among 464 women, 47.8% (222 of 464) had a first-line indication for MHT; however, only 11.8% (55 of 464) reported ever using MHT and 5.6% (26 of 464) were current users. Only 44.8% had ever discussed menopause with their care provider despite almost all women having regular HIV care (97.8%). African/Caribbean/Black women had lower unadjusted odds of MHT treatment compared with White women [odds ratio (OR) 0.42 (0.18–0.89); P = 0.034]. Those who had discussed menopause with their care provider had higher odds of treatment [OR 3.13 (1.74–5.86); P < 0.001]. In adjusted analyses, only women having had a menopause discussion remained significantly associated with MHT use [OR 2.97 (1.62–5.61); P < 0.001].

Conclusion:
Women living with HIV are seldom prescribed MHT despite frequent indication. MHT uptake was associated with care provider–led menopause discussions underscoring the need for care provider education on menopause management within HIV care.
Integrated Single-cell and Plasma Proteomic Modeling to Predict Surgical Site Complications: A Prospective Cohort Study
Authors: Rumer Kristen K. , Hedou Julien , Tsai Amy , Einhaus Jakob , Verdonk Franck , Stanley Natalie , Choisy Benjamin , Ganio Edward , Bonham Adam , Jacobsen Danielle , Warrington Beata , Gao Xiaoxiao , Tingle Martha , McAllister Tiffany N. , Fallahzadeh Ramin , Feyaerts Dorien , Stelzer Ina , Gaudilliere Dyani , Ando Kazuo , Shelton Andrew , Morris Arden , Kebebew Electron , Aghaeepour Nima , Kin Cindy , Angst Martin S. , Gaudilliere Brice 
Published: December 2021

Objective:The aim of this study was to determine whether single-cell and plasma proteomic elements of the host's immune response to surgery accurately identify patients who develop a surgical site complication (SSC) after major abdominal surgery.Summary Background Data:SSCs may occur in up to 25% of patients undergoing bowel resection, resulting in significant morbidity and economic burden. However, the accurate prediction of SSCs remains clinically challenging. Leveraging high-content proteomic technologies to comprehensively profile patients’ immune response to surgery is a promising approach to identify predictive biological factors of SSCs.Methods:Forty-one patients undergoing non-cancer bowel resection were prospectively enrolled. Blood samples collected before surgery and on postoperative day one (POD1) were analyzed using a combination of single-cell mass cytometry and plasma proteomics. The primary outcome was the occurrence of an SSC, including surgical site infection, anastomotic leak, or wound dehiscence within 30 days of surgery.Results:A multiomic model integrating the single-cell and plasma proteomic data collected on POD1 accurately differentiated patients with (n = 11) and without (n = 30) an SSC [area under the curve (AUC) = 0.86]. Model features included coregulated proinflammatory (eg, IL-6- and MyD88- signaling responses in myeloid cells) and immunosuppressive (eg, JAK/STAT signaling responses in M-MDSCs and Tregs) events preceding an SSC. Importantly, analysis of the immunological data obtained before surgery also yielded a model accurately predicting SSCs (AUC = 0.82).Conclusions:The multiomic analysis of patients’ immune response after surgery and immune state before surgery revealed systemic immune signatures preceding the development of SSCs. Our results suggest that integrating immunological data in perioperative risk assessment paradigms is a plausible strategy to guide individualized clinical care.
Association Between Surgical Opioid Prescriptions and Opioid Initiation by Opioid-naïve Spouses
Authors: Varady Nathan H. , Chen Antonia F. , Niu Ruijia , Chung Mei , Freccero David M. , Smith Eric L. 
Published: December 2021

Objective:
To determine whether surgical opioid prescriptions are associated with increased risk of opioid initiation by operative patients’ spouses.

Summary of Background Data:
Adverse effects of surgical opioids on operative patients have been well described. Whether risks of surgical opioids extend to operative patients’ family members is unknown.

Methods:
This was a retrospective cohort study of opioid-naïve, married patients undergoing 1 of 11 common surgeries from January 1, 2011 to June 30, 2017. The adjusted association between surgical opioid prescriptions and opioid initiation by the operative patient’s spouse in the 6-months after surgery was assessed. Secondary analyses assessed how this association varied with postoperative time.

Results:
There were 318,022 patients (mean ± standard deviation age 48.8 ±9.3 years; 49.5% women). Among the 50,833 (16.0%) patients that did not fill a surgical opioid prescription, 2152 (4.2%) had spouses who filled an opioid prescription within 6-months of their surgery. In comparison, among the 267,189 (84.0%) patients who filled a surgical opioid prescription, 15,026 (5.6%) had spouses who filled opioid prescriptions within 6-months of their surgery [unadjusted P < 0.001; adjusted odds ratio (aOR) 1.37, 95% confidence interval (CI) 1.31–1.43, P < 0.001]. Associated risks were only mildly elevated in postoperative month 1 (aOR 1.11, 95% CI 1.00–1.23, P = 0.04) before increasing to a peak in postoperative month 3 (aOR 1.57,95% CI 1.391.76, P < 0.001).

Conclusions:
Surgical opioid prescriptions were associated with increased risk of opioid initiation by spouses of operative patients, suggesting that risks associated with surgical opioids may extend beyond the surgical patient. These findings may highlight the importance of preoperative counseling on safe opioid use, storage, and disposal for both patients and their partners.
Revised Nodal Staging Integrating Tumor Deposit Counts With Positive Lymph Nodes in Patients With Stage III Colon Cancer
Authors: Pyo Dae Hee , Kim Seok Hyung , Ha Sang Yoon , Yun Seong Hyeon , Cho Yong Beom , Huh Jung Wook , Park Yoon Ah , Shin Jung Kyong , Lee Woo Yong , Kim Hee Cheol 
Published: December 2021

Objective:
We evaluated the prognostic value of tumor deposit (TD) counts and incorporated them with the number of positive lymph nodes to develop a revised nodal staging.

Summary Background Data:
The current American Joint Committee on Cancer (AJCC) staging on colon cancer includes the TDs only for nodenegative patients, as N1c, and their counts are not considered.

Methods:
We included consecutive patients with stage III colorectal cancer who underwent curative resections between January 2010 and December 2019. The patients were grouped as TD 0, TD 1, TD 2, or TD ≥3 based on their TD counts. Disease-free survival and overall survival were compared.

Results:
Of 2446 eligible stage III patients, 658 (26.9%) had TDs. Among them, 500 (76.0%) patients concurrently had positive lymph nodes (LNs). TD counts were significantly related to worse disease-free survival (DFS) and overall survival regardless of pT stages or the number of positive LNs. The patients were restaged based on the integrated number of TD counts and positive LNs. The N3 stage, which had ≥10 integrated TDs and positive LNs, was newly classified. Among the patients who completed 6 months of adjuvant chemotherapy, those upstaged to N2 from an initial stage of N1 experienced significantly worse DFS than those confirmed as N1 in the revised N staging. The newly N3-staged patients showed significantly worse DFS than the patients initially staged as N2.

Conclusions:
Revised N staging using the integrated number of TD counts and positive LNs could predict DFS more accurately than current staging. It would also draw greater attention to the patients with high-risk stage III colon cancer staged as N3.
Mesenchymal stem cells after the proprocessing of tanshinone IIA attenuate cognitive deficits and oxidative stress injury in an amyloid β-peptide (25–35)-induced rodent model of Alzheimer’s disease
Authors: Ba Zhisheng , Shi Shangpeng , Huang Nanqu , Li Yuanyuan , Huang Juan , You Chao , Yang Xiaoyan , Liu Daishun , Yu Changyin , He Yuqi , Luo Yong 
Published: December 2021

Objectives
To verify whether mesenchymal stem cells cocultured with tanshinone IIA may ameliorate Alzheimer’s disease by inhibiting oxidative stress.

Methods
Sixty male Sprague–Dawley rats were randomly divided into 4 groups named Sham, Aβ25–35, mesenchymal stem cells, and mesenchymal stem cells (tanshinone IIA). The rats were treated according to different groups. The neurobehavioral performance of Sprague–Dawley rats was evaluated via Morris water maze test. Histological changes were checked via hematoxylin-eosin staining. The levels of total antioxidant activity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and malondialdehyde in hippocampus were assayed by ELISA kit. The levels of Aβ, p-tau/tau, and p-AMP-activated protein kinase/AMP-activated protein kinase in hippocampus were checked by Western blot.

Results
Our research showed that the injection of mesenchymal stem cells (tanshinone IIA) into the hippocampus alleviated learning and memory deficits and reduced hippocampal neuronal injury in the Alzheimer’s disease rats. Moreover, mesenchymal stem cells (tanshinone IIA) treatment suppressed oxidative stress, attenuated Aβ accumulation reduced Tau hyperphosphorylation, and enhanced the activity of AMP-activated protein kinase in the hippocampus of the Alzheimer’s disease rats. However, there were almost no significant difference between the mesenchymal stem cells and Aβ25–35 groups.

Conclusions
Mesenchymal stem cells (tanshinone IIA) transplantation may be a potential treatment for curing Alzheimer’s disease, which may be related to the inhibition of oxidative stress.
Ginsenoside Rg1 inhibits oxidative stress and inflammation in rats with spinal cord injury via Nrf2/HO-1 signaling pathway
Authors: Zhang Zhen , Yang Kun , Mao Rui , Zhong Donghai , Xu Zehua , Xu Jie , Xiong Min 
Published: December 2021

Objectives
In this study, our objective was to investigate the underlying mechanism of the neuroprotective role of ginsenoside Rg1 in attenuating spinal cord injury (SCI).

Methods
A rat SCI model was established and treated with ginsenoside Rg1 and nuclear factor erythroid 2-related factor2(Nrf2) inhibitor all-trans retinoic acid (ATRA). The protective effects of ginsenoside Rg1 were evaluated by Basso, Beattie and Bresnahan (BBB) scale, hematoxylin/eosin staining, ELISA assay, western blotting and quantitative reverse transcription PCR (RT-qPCR).

Results
Ginsenoside Rg1 alleviated neuronal edema and bleeding in the injured spinal cord, reduced inflammatory cell infiltration and cell necrosis, further repaired the injured spinal cord structure, improved BBB motor score in the SCI rat model and improved hind limb motor function. Meanwhile, ginsenoside Rg1 significantly increased the content of antioxidant enzymes superoxide dismutase and glutathione, and inhibited the production of oxidative marker malondialdehyde. In addition, ginsenoside Rg1also significantly inhibits the activities of the inflammatory factors tumor necrosis factor-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) to reduce the inflammatory response after trauma. Furthermore, western blot and RT-qPCR also suggested that ginsenoside Rg1 could activate the protein expression of Nrf2 and heme oxygenase-1 (HO-1) after SCI, and the inhibition of ATRA on these improvements further verified the neuroprotective effect of Nrf2 and HO-1 in ginsenoside Rg1 on SCI.

Conclusion
Ginsenoside Rg1 has a neuroprotective effect on SCI and can improve motor dysfunction caused by injury. The underlying mechanism may play antioxidative stress and anti-inflammatory effect by regulating the Nrf2/HO-1 signaling pathway.
The activation of hypothalamic AMP-activated protein kinase by oxidative stress is related to hyperphagia in diabetic rats
Authors: Mendoza-Bello Juan M. , Barragán-Bonilla Martha I. , Ramírez Mónica , Flores-Alfaro Eugenia , Millán-Vega Alejandro , Parra-Abarca Juan , Espinoza-Rojo Mónica 
Published: December 2021

Objective
During diabetes, there are increased blood glucose levels and oxidative stress. The relationship between oxidative stress and the phosphorylation of AMP-activated protein kinase at the hypothalamic level has been little studied. The objective of this study was to analyze the relationship between oxidative stress and AMP-activated protein kinase activation in Wistar rats with hyperphagia and hyperglycemia.

Methods
Rats at 7, 14, and 28 days with diabetes were used. Control rats were included. Food intake was calculated to determine hyperphagia. The hypothalamus was extracted to evaluate oxidative stress markers by spectrophotometry; phosphorylation of AMP-activated protein kinase, growth hormone receptor 1a, and neuropeptide Y expression were determined by Western blot.

Results
There was a significant increase in the consumption of food in the experimental groups. The level of malondialdehyde decreased in the 7-day group (33%) and increased significantly in the 28-day group (90%), glutathione peroxidase activity increased in the 7-day group (70%) and decreased in the 28-day group (34%), and the phosphorylation of AMP-activated protein kinase increased significantly in the 28-day group (86%). Under ex-vivo conditions in animals with 28 days of hyperglycemia, glutathione peroxidase activity increased 195%, the malondialdehyde level decreased 87%, phosphorylation of AMP-activated protein kinase decreased 53%, and growth hormone receptor 1a expression decreased 66%, when treating hyperglycemic hypothalamic tissue with an antioxidant. NPY expression increased in hyperglycemia, and antioxidant treatment did not regulate its expression.

Conclusions
The activation of AMP-activated protein kinase is related with an increase in oxidative stress markers in hyperglycemic and hyperphagic rats.
The neural bases of vertebrate motor behaviour through the lens of evolution
Authors: Suryanarayana Shreyas M. , Robertson Brita , Grillner Sten 
Published: December 2021

The primary driver of the evolution of the vertebrate nervous system has been the necessity to move, along with the requirement of controlling the plethora of motor behavioural repertoires seen among the vast and diverse vertebrate species. Understanding the neural basis of motor control through the perspective of evolution, mandates thorough examinations of the nervous systems of species in critical phylogenetic positions. We present here, a broad review of studies on the neural motor infrastructure of the lamprey, a basal and ancient vertebrate, which enjoys a unique phylogenetic position as being an extant representative of the earliest group of vertebrates. From the central pattern generators in the spinal cord to the microcircuits of the pallial cortex, work on the lamprey brain over the years, has provided detailed insights into the basic organization (abauplan) of the ancestral vertebrate brain, and narrates a compelling account of common ancestry of fundamental aspects of the neural bases for motion control, maintained through half a billion years of vertebrate evolution.This article is part of the theme issue ‘Systems neuroscience through the lens of evolutionary theory’.
Evolution of behavioural control from chordates to primates
Authors: Cisek Paul 
Published: December 2021

This article outlines a hypothetical sequence of evolutionary innovations, along the lineage that produced humans, which extended behavioural control from simple feedback loops to sophisticated control of diverse species-typical actions. I begin with basic feedback mechanisms of ancient mobile animals and follow the major niche transitions from aquatic to terrestrial life, the retreat into nocturnality in early mammals, the transition to arboreal life and the return to diurnality. Along the way, I propose a sequence of elaboration and diversification of the behavioural repertoire and associated neuroanatomical substrates. This includes midbrain control of approach versus escape actions, telencephalic control of local versus long-range foraging, detection of affordances by the dorsal pallium, diversified control of nocturnal foraging in the mammalian neocortex and expansion of primate frontal, temporal and parietal cortex to support a wide variety of primate-specific behavioural strategies. The result is a proposed functional architecture consisting of parallel control systems, each dedicated to specifying the affordances for guiding particular species-typical actions, which compete against each other through a hierarchy of selection mechanisms.
This article is part of the theme issue ‘Systems neuroscience through the lens of evolutionary theory’.