bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular pathways dysregulated by Pb2+ exposure prompts pancreatic beta-cell dysfunction
Authors: Daniel P Vineeth , Kamthan Mohan , Thakur Shilpa , Mondal Prosenjit 
Published: December 2021

Abstract
Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by reduced insulin sensitivity and dysfunction of β-cells. Although the increasing prevalence of diabetes worldwide is largely attributed to genetic predisposition or lifestyle factors (insufficient physical activity), and caloric intake. Environmental factors, exposure to xenobiotics and heavy metals have also been reported to be causative factors of T2DM. At this juncture, we, through our work unveil a plausible link between Pb2+ exposure and diabetes mellitus, and delineated a comprehensive understanding of the potential mechanisms of Pb2+-induced β-cells dysfunction. In our in vivo observations, we found that Pb2+ exposure strongly reduced glucose-stimulated insulin secretion and diminished functional pancreatic β-cell mass. Mechanistically, we found that Pb2+ downregulates intracellular cAMP level via hyper-activating Ca2+/calmodulin-dependent 3′,5′-cyclic nucleotide phosphodiesterase 1C and thereby reduces glucose-stimulated insulin secretion. Further, we report that Pb2+ inhibited mitochondrial adenosine triphosphate production and also identified Pb2+ as a negative regulator of β-cell proliferation via Ca2+/calmodulin-dependent protein kinase kinases-pAMPK-pRaptor axis. Together, our findings strongly reinforce Pb2+ to hijack the physiological role of calcium ions, by mimicking Ca2+ within pancreatic β-cell and thereby stands as a diabetogenic xenobiotic.
Trends in and Maternal Outcomes of Delivery Hospitalizations of Patients With an Asthma Diagnosis
Authors: Friedman Alexander M. , DiMango Emily A. , Guglielminotti Jean R. , Huang Yongmei , Wright Jason D. , D'Alton Mary E. , Wen Timothy 
Published: December 2021

OBJECTIVE:
To characterize asthma prevalence and outcomes during U.S. delivery hospitalizations.

METHODS:
For this repeated cross-sectional analysis, deliveries to women aged 15–54 years with asthma were identified in the 2000–2018 National Inpatient Sample, which approximates a 20% stratified sample of all hospitalizations nationally. Temporal trends in asthma were analyzed using joinpoint regression to estimate the average annual percent change with 95% CIs. The association of asthma with other comorbid conditions was analyzed. The relationship between asthma and several adverse maternal outcomes was analyzed with unadjusted and adjusted logistic regression models, with unadjusted odds ratios and adjusted odds ratios (aORs) as measures of effect. Risk for and trends in a composite of rare, but severe, respiratory complications also were analyzed.

RESULTS:
An estimated 73,109,790 delivery hospitalizations from 2000 to 2018 were included in the analysis, of which 2,221,644 (3.0%) had a diagnosis of asthma. (Unweighted, the study sample included 15,213,024 deliveries, of which 462,276 [3.0%] had a diagnosis of asthma.) Asthma diagnoses rose from 1.2% in 2000 to 5.3% in 2018, representing an average annual percent change of 8.3% (95% CI 7.4–9.2%). Asthma was more common among women with obesity and chronic hypertension. In adjusted analyses, asthma was associated with severe maternal morbidity (aOR 1.50, 95% CI 1.45–1.55), preeclampsia and gestational hypertension (aOR 1.29, 95% CI 1.26–1.30), postpartum hemorrhage (aOR 1.21, 95% CI 1.19–1.24), cesarean delivery (aOR 1.16, 95% CI 1.15–1.18), gestational diabetes (aOR 1.20, 95% CI 1.18–1.21), venous thromboembolism (aOR 1.79, 95% CI 1.65–1.95), and preterm delivery (aOR 1.27, 95% CI 1.25–1.29). From 2000 to 2018, severe respiratory complications decreased from 72 per 10,000 deliveries with asthma to 14 per 10,000 deliveries with asthma (average annual percent change −9.4%, 95% CI −13.3% to −5.3%). This decreasing risk was offset on a population level by an increase in the risk of asthma.

CONCLUSION:
Asthma is increasing during deliveries, is associated with adverse maternal outcomes, and is associated with comorbid conditions. Severe respiratory complications are decreasing proportionately among deliveries with asthma, but are stable on a population basis.
Blood Pressure in Critically Ill Children: Exploratory Analyses of Concurrent Invasive and Noninvasive Measurements
Authors: Goodwin Andrew , Mazwi Mjaye L. , Somer Jonathan , Schwartz Steven M. , McEwan Alistair , Eytan Danny 
Published: December 2021

OBJECTIVES:
Differences and biases between directly measured intra-arterial blood pressure and intermittingly measured noninvasive blood pressure using an oscillometric cuff method have been reported in adults and children. At the bedside, clinicians are required to assign a confidence to a specific blood pressure measurement before acting upon it, and this is challenging when there is discordance between measurement techniques. We hypothesized that big data could define and quantify the relationship between noninvasive blood pressure and intra-arterial blood pressure measurements and how they can be influenced by patient characteristics, thereby aiding bedside decision-making.

DESIGN:
A retrospective analysis of cuff blood pressure readings with associated concurrent invasive arterial blood pressure measurements (452,195 noninvasive blood pressure measurements).

SETTING:
Critical care unit at The Hospital for Sick Children, Toronto.

PATIENTS:
Six-thousand two-hundred ninety-seven patients less than or equal to 18 years old, hospitalized in a critical care unit with an indwelling arterial line.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Two-dimensional distributions of intra-arterial blood pressure and noninvasive blood pressure were generated and the conditional distributions of intra-arterial blood pressure examined as a function of the noninvasive systolic, diastolic, or mean blood pressure. Modification of these distributions according to age and gender were examined using a multilevel mixed-effects model. For any given combination of patient age and noninvasive blood pressure, the expected distribution of intra-arterial blood pressure readings exhibited marked variability at the population level and a bias that significantly depended on the noninvasive blood pressure value and age. We developed an online tool that allows exploration of the relationship between noninvasive blood pressure and intra-arterial blood pressure and the conditional probability distributions according to age.

CONCLUSIONS:
A large physiologic dataset provides clinically applicable insights into the relationship between noninvasive blood pressure and intra-arterial blood pressure measurements that can help guide decision-making at the patient bedside.
Society for Developmental & Behavioral Pediatrics Position Statement on Telehealth
Authors: Keder Robert D. , Mittal Shruti , Stringer Kimberlly , Wallis Kate E. , Wallace Jenna E. , Soares Neelkamal S. 
Published: December 2021

ABSTRACT:
Telehealth has long held promise as a way to increase access to subspecialty care for children and families, including in developmental and behavioral pediatrics (DBP). The coronavirus disease 2019 (COVID-19) pandemic necessitated rapid uptake of telehealth to continue care delivery that was facilitated by “temporary” policy changes related to the pandemic. As a result, the field of DBP has recognized telehealth as a potential model of care for performing home-based diagnostic assessments, providing medication management follow-up, and delivering therapeutic interventions for children with neurodevelopmental disorders. Telehealth has been helpful in mitigating barriers families often face when attending in-person visits (lack of transportation and child care, missed work hours, etc) but has also highlighted additional determinants of health that need to be addressed to provide equitable access to care (broadband connectivity, device access, digital literacy, access to interpretation and sign language services, etc). Anticipating the lifting of pandemic-related emergency declaration and expiration of temporary policies around telehealth, the ability to continue to deliver DBP care by telehealth is uncertain. The purpose of this policy statement is to advocate for legislation and policies that support ongoing, equitable, home-based telehealth care for patients seen by DBP providers while ensuring equitable access to DBP in general. In addition, there is a need to recognize the benefits and challenges of telehealth versus in-person care and to identify clinical scenarios that favor 1 model of care versus the other.
A Pregnant Mother Infected With Severe Acute Respiratory Syndrome Coronavirus 2 With Substance Dependence
Authors: Nagdi Dorabati Peymaneh , Khoshnam rad Mahsa , Hedayat Yaghoobi Mojtaba , Mahmoodi Zohreh 
Published: December 2021

Abstract

Background
In December 2019, the novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China, and now, it has spread all over the world. Pregnant women are a susceptible population, but there is scant information about COVID-19 in this population. Here, we report a case of a mother with substance use disorders who was infected with COVID-19 in her pregnancy.

Case
The patient was a 29-year-old, primigravida mother at the 37th gestational week who was referred to our center because of vaginal bleeding and severe uterine contractions. The patient was abusing opioids. With the suspicion of placental abruption, she was admitted for cesarean section. One day after delivery, she developed dyspnea, rhinorrhea, and vomiting. These were thought of as withdrawal signs. Despite methadone administration, these signs persisted. After ruling out deprivation syndrome and possible obstetric causes, a SARS-CoV-2 Polymerase chain reaction (PCR) test was ordered; the result was positive.

Conclusion
In this case, because of the flu-like symptoms of substance withdrawal and postpartum causes of shortness of breath, the medical team's attention was drawn to these causes. SARS-CoV-2 infection should be considered as a differential diagnosis for these patients.
It's Not Denial, It's Stigma
Authors: Harding Shari 
Published: December 2021

Abstract
Addictions nurses often encounter barriers to care for clients such as stigma, especially in settings outside addictions specialty care. This article utilizes a case-study format to show and discuss concepts related to client engagement in recovery and overcoming stigma. Laura, a 65-year-old woman, presents with a worsening of her alcohol use disorder in the setting of a recent retirement, worsening symptoms of major depressive disorder, and the stressors associated with the COVID-19 pandemic. She presents with her depression and is reluctant to discuss her alcohol use, after a past experience in a program that utilized a confrontational approach. Her primary care provider describes her as “in denial,” but this case study will discuss elements including stigma, self-stigma, and the culture of addictions treatment and their impact on recovery. Finally, this presentation will describe how the addictions nurse can leverage a person-centered and recovery-oriented approach to promote engagement and positive problem solving with the client and the care team.
Clinical Utility of the Signal-to-Cutoff Ratio of Reactive HIV Antigen/Antibody Screening Tests in Guiding Emergency Physician Management
Authors: White Douglas A. E. , Anderson Erik S. , Basham Kellie , Ng Valerie L. , Russell Carly , Lyons Michael S. , Powers-Fletcher Margaret V. , Giordano Thomas P. , Muldrew Kenneth L. , Siatecka Hanna , Hsieh Yu-Hsiang , Dashler Gaby , Carroll Karen C. , Mostafa Heba H. , Rothman Richard E. 
Published: December 2021

Background:
The signal-to-cutoff (S/CO) ratio of the HIV antigen/antibody test may help immediately to differentiate true-positive results from false-positive results, which may be particularly useful in time-sensitive circumstances, such as when providing emergency department (ED) care.

Setting:
Seven US EDs with HIV screening programs using HIV antigen/antibody assays.

Methods:
This cross-sectional study of existing data correlated S/CO ratios with confirmed HIV status. Test characteristics at predetermined S/CO ratios and the S/CO ratio with the best performance by receiver operator characteristic (ROC) curve were calculated.

Results:
Of 1035 patients with a reactive HIV antigen/antibody test, 232 (22.4%) were confirmed HIV-negative and 803 (77.6%) were confirmed HIV-positive. Of the 803 patients, 713 (88.8%) experienced chronic infections and 90 (11.2%) experienced acute infections. S/CO ratios were greater for HIV-positive (median 539.2) than for HIV-negative patients (median 1.93) (P < 0.001) and lower for acute infection (median 22.8) than for chronic infection (median 605.7) (P < 0.001). All patients with an S/CO ratio < 1.58 (n = 93) were HIV-negative (NPV 100%), and nearly all with an S/CO ≥ 20.7 (n = 760) (optimal level by ROC analysis) were HIV-positive (PPV 98.6%). Of patients with S/CO values between 1.58 and 20.7 (n = 182), 29.7% were HIV-positive.

Conclusions:
The S/CO ratio may be used in real time to classify most ED patients as almost certain to be either HIV-positive or HIV-negative long before nucleic acid confirmatory testing is available. When combined with clinical judgment, this could guide preliminary result disclosure and management.
Use of Indocyanine Green Angiography to Identify the Superficial Temporal Artery and Vein in Forehead Flaps for Facial Reconstruction
Authors: Zang Mengqing , Zhu Shan , Chen Bo , Li Shanshan , Han Tinglu , Liu Yuanbo 
Published: December 2021

Abstract:
The superficial temporal artery (STA) frontal branch flap is susceptible to venous congestion because of its unpredictable and variable outflow. The authors applied indocyanine green angiogra-phy in identifying the superficial temporal vessels to help surgeons with proper flap designs to avoid severe complications. A retrospective review from 2015 to 2020 was conducted. All the patients who underwent indocyanine green angiography before forehead flap transfer for facial defect reconstruction were reviewed. The STA and vein were observed using indocyanine green angiography preoperatively. The relationship between the artery and vein was investigated. The venous anatomy was analyzed to guide the pedicle design. The survival of the flap and complications were assessed. A total of 12 patients were identified and included in this study. Indocyanine green angiography allows clear visualization of the detailed anatomy of the STA and vein. The frontal branch of the vein had great variations and generally diverged from the arterial branch. The tiny venae comitantes provided sufficient drainage for 2 small forehead flaps. The frontal branch of the vein entered the forehead and was used as the outflow channel in 4 patients. The parietal branch of the vein, which consistently gave off secondary tributaries to the superior forehead, was included in the pedicle in 6 patients. All flaps survived without complications. indocyanine green angiography provided accurate localization of the superficial temporal vessels. This technique may be helpful in the precise planning forehead flap surgeries and in avoiding the risk of venous congestion.
Inexpensive and colorimetric RNA detection by E. coli cell-free protein synthesis platform at room temperature
Authors: Notarangelo Michela , Quattrone Alessandro , Pizzato Massimo , Mansy Sheref S. , Toparlak Ö. Duhan 
Published: December 2021

ABSTRACTWe report colorimetric detection of SARS-CoV-2 viral RNA by an in vitro transcription/translation assay with crude E. coli extracts at room temperature, with the aid of body heat. Clinically-relevant concentrations of viral RNA (ca. 600 copies/test) were detected from synthetic RNA samples. The activation of cell-free gene expression was achieved by toehold-switch-mediated riboregulatory elements that are specific to viral RNA sequences. The colorimetric output was generated by the α-complementation of β-galactosidase ω-fragment (LacZω) with cell-free expressed LacZα, using an X-gal analogue as a substrate. The estimated cost of single reaction is <€1/test, which may facilitate diagnostic kit accessibility in developing countries.
A simple model of COVID-19 explains disease severity and the effect of treatments
Authors: Sanche Steven , Cassidy Tyler , Chu Pinghan , Perelson Alan S. , Ribeiro Ruy M. , Ke Ruian 
Published: December 2021

ABSTRACTConsiderable effort was made to better understand why some people suffer from severe COVID-19 while others remain asymptomatic. This has led to important clinical findings; people with severe COVID-19 generally experience persistently high levels of inflammation, slower viral load decay, display a dysregulated type-I interferon response, have less active natural killer cells and increased levels of neutrophil extracellular traps. How these findings are connected to the pathogenesis of COVID-19 remains unclear. We propose a mathematical model that sheds light on this issue. The model focuses on cells that trigger inflammation through molecular patterns: infected cells carrying pathogen-associated molecular patterns (PAMPs) and damaged cells producing damage-associated molecular patterns (DAMPs). The former signals the presence of pathogens while the latter signals danger such as hypoxia or the lack of nutrients. Analyses show that SARS-CoV-2 infections can lead to a self-perpetuating feedback loop between DAMP expressing cells and inflammation. It identifies the inability to quickly clear PAMPs and DAMPs as the main contributor to hyperinflammation. The model explains clinical findings and the conditional impact of treatments on disease severity. The simplicity of the model and its high level of consistency with clinical findings motivate its use for the formulation of new treatment strategies.
Racial and ethnic disparities in maternal mental health during COVID-19
Authors: Iyengar Ananya S. , Ein-Dor Tsachi , Zhang Emily X. , Chan Sabrina J. , Kaimal Anjali J. , Dekel Sharon 
Published: December 2021

AbstractKnowledge of childbirth outcomes of Black and Latinx individuals during the coronavirus pandemic is limited. Black/African American and Latinx/Hispanic individuals were matched to non-Hispanic white individuals on socio-demographics. Minority individuals were nearly three times more likely to have clinically significant traumatic stress in response to childbirth and two times more likely to report postpartum depression. Unplanned Cesarean rates were higher and incidences of skin-to-skin and breastfeeding were lower in the minority group. Racial and ethnic maternal disparities exist during COVID-19.
Danger signs and management of suspected severe malaria cases at community level and in referral health facilities: an operational study in the Democratic Republic of the Congo
Authors: Okitawutshu Jean , Signorell Aita , Kalenga Jean-Claude , Mukomena Eric , Delvento Giulia , Burri Christian , Mwaluke Fatou , Buj Valentina , Sangare Moulaye , Luketa Sylvie , Brunner Nina , Lee Tristan , Hetzel Manuel , Lengeler Christian , Tshefu Antoinette 
Published: December 2021

AbstractBackgroundEvidence from one trial in Africa suggests that pre-referral Rectal Artesunate (RAS) can be a life-saving intervention for severe malaria in remote settings, where parenteral treatment is not available. Recognition of danger signs indicative of severe malaria is critical for prompt and appropriate case management.MethodsAn observational study was conducted in the Democratic Republic of the Congo (DRC) in the frame of the multi-country CARAMAL project, to assess the effectiveness of RAS under real-world conditions. Severely ill feverish children <5 years seeking care from a community-based healthcare provider were recruited in three rural health zones into a patient surveillance system. They were subsequently followed within the healthcare system and at home after 28 days to determine care seeking, antimalarial treatment provision and health outcomes.ResultsOverall, 66.4% of patients had iCCM general danger signs, as well as more specific danger signs. Children aged 2-5 years (aOR=1.58, 95% CI 1.20–2.08) and those presenting iCCM general danger signs were more likely to receive RAS (aOR = 2.77, 95% CI 2.04–3.77). Injectable treatment was less likely with RAS pre-referral treatment (aOR=0.21, 95% 0.13– 0.33). In the post-RAS phase, the case fatality ratio was 7.1%. Children not receiving RAS had a higher risk of dying, but this was not statistically significant (aOR = 1.50, 95% CI 0.86– 2.60). The odds of dying were reduced in patients without iCCM general danger signs, but just not statistically so (aOR = 0.64, 95% CI 0.38–1.06). Full oral therapy at a RHF was highly protective (aOR = 0.13, 95% CI 0.07-0.26), while a full treatment of severe malaria (injectable + oral) was shown to also decrease massively the odds of dying (aOR = 0.26, 95% CI 0.09– 0.79) compared to injectable treatment alone.ConclusionsBetter understanding the determinants of successful case management, and targeted improvements of the health system (especially the provision of a full course of an oral antimalarial) are crucial for improving health oucomes of children with suspected severe malaria.
Direct lysis RT-qPCR of SARS-CoV-2 in cell culture supernatant allows for fast and accurate quantification of virus, opening a vast array of applications
Authors: Craig Nicky , Fletcher Sarah L. , Daniels Alison , Newman Caitlin , O’Shea Marie , Warr Amanda , Tait-Burkard Christine 
Published: December 2021

ABSTRACTAn enormous global effort is being made to study SARS-CoV-2 and develop safe and effective treatments. Studying the entire virus replication cycle of SARS-CoV-2 is essential to identify host factors and treatments to combat the infection. However, quantification of released virus often requires lengthy procedures, such as endpoint dilution assays or reinfection with engineered reporter viruses. Quantification of viral RNA in cell supernatant is faster and can be performed on clinical isolates. However, viral RNA purification is expensive in time and resources and often unsuitable for high-throughput screening. Here, we show a direct lysis RT-qPCR method allowing sensitive, accurate, fast, and cheap quantification of SARS-CoV-2 in culture supernatant. During lysis, the virus is completely inactivated, allowing further processing in low containment areas. This protocol facilitates a wide array of high- and low-throughput applications from basic quantification to studying the biology of SARS-CoV-2 and to identify novel antiviral treatmentsin vitro.