bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of embryonal tumors with multilayered rosettes with carboplatin/etoposide induction and high-dose chemotherapy within the prospective P-HIT trial
Authors: Juhnke B-Ole , Gessi Marco , Gerber Nicolas U , Friedrich Carsten , Mynarek Martin , von Bueren André O , Haberler Christine , Schüller Ulrich , Kortmann Rolf-Dieter , Timmermann Beate , Bison Brigitte , Warmuth-Metz Monika , Kwiecien Robert , Pfister Stefan M , Spix Claudia , Pietsch Torsten , Kool Marcel , Rutkowski Stefan , von Hoff Katja
Published: April 2021

Background

Embryonal tumors with multilayered rosettes (ETMR) are highly aggressive tumors occurring in early childhood. Published clinical data refer to retrospective, heterogeneously treated cohorts. Here, we describe the outcome of patients treated according to the prospective P-HIT trial and subsequent HIT2000-interim-registry.

Patients and methods

Age-stratified treatment included carboplatin/etoposide induction, tandem high-dose chemotherapy (“CARBO/ETO + HDCT”), and response-stratified radiotherapy. Patients with centrally reviewed neuropathological and molecularly confirmed diagnosis of ETMR recruited within the P-HIT trial (2001-2011; n = 19), the HIT2000-interim-registry (2012-2014; n = 12), and earlier HIT trials (n = 4) were selected for analysis.

Results

Age-adjusted incidence rate was 1.35 per 1 million children (aged 1-4 years) in the years 2012-2014. Median age at diagnosis for 35 patients was 2.9 years. Metastases at diagnosis were detected in 9 patients. One patient died due to postoperative complications. For 30 patients with non-brainstem tumor location, 5-year progression-free survival (PFS) and overall survival (OS) were 35% and 47% after treatment with CARBO/ETO + HDCT (n = 17), compared to 0% and 8% with other treatments (n = 13, P[OS] = .011). All 4 patients with brainstem tumor died within 10 months after diagnosis. By multivariable analysis, supratentorial location: (HR [PFS]: 0.07 [95%CI: 0.01-0.38], P = .003), localized disease (M0): (HR [OS] M0, no residual tumor: 0.30 [95%CI: 0.009-1.09], P = .068; M0, residual tumor: 0.18 [95%CI: 0.04-0.76], P = .020), and CARBO/ETO + HDCT treatment (HR [OS]: 0.16 [95%CI: 0.05-054], P = .003) were identified as independent prognostic factors. Of 9 survivors, 6 were treated with radiotherapy (craniospinal 4; local 2).

Conclusions

Our data indicate improved survival with intensified chemotherapy (CARBO/ETO + HDCT). However, despite intensive treatment, the outcome was poor. Thus, innovative therapies need to be evaluated urgently in an upfront setting.
Irradiation of Nf1 mutant mouse models of spinal plexiform neurofibromas drives pathologic progression and decreases survival
Authors: Laurent Danny , Smith Abbi E , Bessler Waylan K , Mendonca Marc , Chin-Sinex Helen , Descovich Martina , Horvai Andrew E , Clapp D Wade , Nakamura Jean L
Published: April 2021

Background

Genetically susceptible individuals can develop malignancies after irradiation of normal tissues. In the context of therapeutic irradiation, it is not known whether irradiating benign neoplasms in susceptible individuals promotes neoplastic transformation and worse clinical outcomes. Individuals with Neurofibromatosis 1 (NF1) are susceptible to both radiation-induced second malignancies and spontaneous progression of plexiform neurofibromas (PNs) to malignant peripheral nerve sheath tumors (MPNSTs). The role of radiotherapy in the treatment of benign neoplasms such as PNs is unclear.

Methods

To test whether radiotherapy promotes neoplastic progression of PNs and reduces overall survival, we administered spinal irradiation (SI) to conditional knockout mouse models of NF1-associated PNs in 2 germline contexts: Nf1fllfl; PostnCre+ and Nf1fl/-; PostnCre+. Both genotypes develop extensive Nf1 null spinal PNs, modeling PNs in NF1 patients. A total of 101 mice were randomized to 0 Gy, 15 Gy (3 Gy × 5), or 30 Gy (3 Gy × 10) of spine-focused, fractionated SI and aged until signs of illness.

Results

SI decreased survival in both Nf1fllfl mice and Nf1fl/- mice, with the worst overall survival occurring in Nf1fl/- mice receiving 30 Gy. SI was also associated with increasing worrisome histologic features along the PN-MPNST continuum in PNs irradiated to higher radiation doses.

Conclusions

This preclinical study provides experimental evidence that irradiation of pre-existing PNs reduces survival and may shift PNs to higher grade neoplasms.
Expression of cell type incongruent alpha-cardiac actin 1 subunit in medulloblastoma reveals a novel mechanism for cancer cell survival and control of migration
Authors: Suresh Rahul , Picard Daniel , Lo Rita , Beaulieu Jamie , Remke Marc , Diaz Roberto Jose
Published: April 2021

Background

Alterations in actin subunit expression have been reported in multiple cancers, but have not been investigated previously in medulloblastoma.

Methods

Bioinformatic analysis of multiple medulloblastoma tumor databases was performed to profile ACTC1 mRNA levels. Western blot was used to verify protein expression in established medulloblastoma cell lines. Immunofluorescence microscopy was performed to assess ACTC1 localization. Stable cell lines with ACTC1 overexpression were generated and shRNA knockdown of ACTC1 was accomplished. We used PARP1 cleavage by Western blot as a marker of apoptosis and cell survival was determined by FACS viability assay and colony formation. Cell migration with overexpression or knockdown of ACTC1 was determined by the scratch assay. Stress fiber length distribution was assessed by fluorescence microscopy.

Results

ACTC1 mRNA expression is highest in SHH and WNT medulloblastoma among all subgroups. ACTC1 protein was confirmed by Western blot in SHH subgroup and Group 3 subgroup cell lines with the lowest expression in Group 3 cells. Microscopy demonstrated ACTC1 co-localization with F-actin. Overexpression of ACTC1 in Group 3 cells abolished the apoptotic response to Aurora kinase B inhibition. Knockdown of ACTC1 in SHH cells and in Myc overexpressing SHH cells induced apoptosis, impaired colony formation, and inhibited migration. Changes in stress fiber length distribution in medulloblastoma cells are induced by alterations in ACTC1 abundance.

Conclusions

Alpha-cardiac actin (ACTC1) is expressed in SHH medulloblastoma. Expression of this protein in medulloblastoma modifies stress fiber composition and functions in promoting resistance to apoptosis induced by mitotic inhibition, enhancing cell survival, and controlling migration.
Python Package abstcal: An Open-Source Tool for Calculating Abstinence From Timeline Followback Data
Authors: Cui Yong , Robinson Jason D , Rymer Rudel E , Minnix Jennifer A , Cinciripini Paul M
Published: April 2021

Introduction

In smoking cessation clinical trials, timeline followback (TLFB) interviews are widely used to track daily cigarette consumption. However, there are no standard tools for calculating abstinence based on TLFB data. Individual research groups have to develop their own calculation tools, which is not only time- and resource-consuming but might also lead to variability in the data processing and calculation procedures.

Aims and Methods

To address these issues, we developed a novel open-source Python package named abstcal to calculate abstinence using TLFB data. This package provides data verification, duplicate and outlier detection, missing-data imputation, integration of biochemical verification data, and calculation of a variety of definitions of abstinence, including continuous, point-prevalence, and prolonged abstinence.

Results

We verified the accuracy of the calculator using data derived from a clinical smoking cessation study. To improve the package’s accessibility, we have made it available as a free web app.

Conclusions

The abstcal package is a reliable abstinence calculator with open-source access, providing a shared validated online tool to the addiction research field. We expect that this open-source abstinence calculation tool will improve the rigor and reproducibility of smoking and addiction research by standardizing TLFB-based abstinence calculation.

Implications

Abstinence calculation is an essential task in any smoking intervention study. However, there have not been standard open-source tools available to the researchers. This commentary describes a Python-based package called abstcal that can calculate abstinence from TLFB data, a common methodology to collect smoking consumption data in research settings. The package supports the calculation of point-prevalence, prolonged, and continuous abstinence. Importantly, the package has a web app interface that allows researchers to use the tool without any coding experience. This tool will facilitate smoking research by providing a standardized and easy-to-use abstinence calculation tool.
Are Boycotts, Shunning, and Shaming Corrupt?
Authors: Altman Scott
Published: April 2021

Boycotts, shunning, and shaming sometimes wrong their targets by offering corrupt incentives that undermine significant individual aims. These tactics unjustly harm targets when they aim to impede living authentically, deterring them from declaring their beliefs in public or pursuing important projects. They are corrupt because they make their targets willing participants in these harms. They subvert their targets’ ambitions not to allow money or social pressure to influence their most important actions. Although individuals must maintain their integrity, people also have a moral responsibility not to undermine those efforts. Not all uses of these tactics conflict with an anti-corruption norm. Many labour and consumer boycotts likely do not threaten authenticity. Other uses arguably pursue non-corrupt aims, such as punishment, norm reinforcement or non-complicity, threatening corruption only as an unintended consequence. Even as to these, several considerations weigh against using boycotts, shunning, and shaming. Using these techniques for punishment and norm reinforcement is often inappropriate in a liberal society. Some uses that appear to aim at non-complicity also aim at corrupting their targets. Finally, sometimes imposing a risk of unintended corruption wrongs those exposed to such risks.
Intracranial Access: Dural Venous Sinus Stenting: 2-Dimensional Operative Video
Authors: Domingo Ricardo A , Ravindran Krishnan , Kulakova Katya , Tawk Rabih G ,   Endovascular Neurosurgery Research Group (ENRG), Arthur Adam , Bain Mark , Bendock Bernard , Binning Mandy Jo , Boulos Alan S , Crowley Webster , Fessler Richard , Grande Andrew , Guterman Lee , Hanel Ricardo , Hoit Daniel , Hopkins L Nelson , Howington Jay , James Robert , Jankowitz Brian , Kan Peter , Khalessi Alex A , Kim Louis , Langer David , Lanzino Giuseppe , Levitt Michael , Levy Elad I , Lopes Demetrius , Mack William , Mericle Robert , Mocco J , Ogilvy Chris , Pandey Aditya , Replogle Robert , Riina Howard , Ringer Andrew , Rodriguez Rafael , Saugaveau Eric , Schirmer Clemens , Siddiqui Adnan H , Spiotta Alex , Sultan Ali , Tawk Rabih , Thomas Ajith , Turner Raymond , Veznedaroglu Erol , Welch Babu , White Jonathan
Published: April 2021

Cerebral venous sinus stenting has gained popularity in recent years as a safe and efficacious treatment of selected patients with idiopathic intracranial hypertension (IIH) and focal venous sinus stenosis.1–3
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3
The main goal of treatment is to prevent visual loss, and often patients report resolution of headache and visual symptoms within 21 mo of mean follow-up.4–8
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8
We present the case of a 57-yr-old woman with medically refractory IIH, bilateral sinus stenosis, and a mass lesion causing stenosis on the left. Venous angiogram with pressure monitoring was completed with the patient awake, which showed a significant pressure gradient on the right (19 mm Hg) and borderline gradient on the left (8 mm Hg). Options were reviewed and decision was made to proceed with the treatment of the right-sided stenosis with stenting and continue with the observation of the lesion on the left to prevent further visual deterioration. The patient consented for the procedure, and she tolerated the procedure well. Neurological exam remained at baseline, and she was discharged home on post-operative day #1. At 2 mo’s follow-up, the patient reported improvement in headaches and remained intact neurologically.
Hydraulic consequences of enzymatic breakdown of grapevine pit membranes
Authors: Fanton Ana Clara , Brodersen Craig
Published: April 2021

Xylella fastidiosa (Xf) is the xylem-dwelling bacterial agent associated with Pierce’s disease (PD), which leads to significant declines in productivity in agriculturally important species like grapevine (Vitis vinifera). Xf spreads through the xylem network by digesting the pit membranes (PMs) between adjacent vessels, thereby potentially changing the hydraulic properties of the stem. However, the effects of Xf on water transport vary depending on the plant host and the infection stage, presenting diverse outcomes. Here, we investigated the effects of polygalacturonase, an enzyme known to be secreted by Xf when it produces biofilm on the PM surface, on stem hydraulic conductivity, and PM integrity. Experiments were performed on six grapevine genotypes with varying levels of PD resistance, with the expectation that PM resistance to degradation by polygalacturonase may play a role in PD resistance. Our objective was to study a single component of this pathosystem in isolation to better understand the mechanisms behind reported changes in hydraulics, thereby excluding the biological response of the plant to the presence of Xf in the vascular system. PM damage only occurred in stems perfused with polygalacturonase. Although the damaged PM area was small (2%–9% of the total pit aperture area), membrane digestion led to significant changes in the median air-seeding thresholds, and most importantly, shifted frequency distribution. Finally, enzyme perfusion also resulted in a universal reduction in stem hydraulic conductivity, suggesting the development of tyloses may not be the only contributing factor to reduced hydraulic conductivity in infected grapevine.
A fragment-based protein interface design algorithm for symmetric assemblies
Authors: Laniado Joshua , Meador Kyle , Yeates Todd O
Published: April 2021

Theoretical and experimental advances in protein engineering have led to the creation of precisely defined, novel protein assemblies of great size and complexity, with diverse applications. One powerful approach involves designing a new attachment or binding interface between two simpler symmetric oligomeric protein components. The required methods of design, which present both similarities and key differences compared to problems in protein docking, remain challenging and are not yet routine. With the aim of more fully enabling this emerging area of protein material engineering, we developed a computer program, nanohedra, to introduce two key advances. First, we encoded in the program the construction rules (i.e. the search space parameters) that underlie all possible symmetric material constructions. Second, we developed algorithms for rapidly identifying favorable docking/interface arrangements based on tabulations of empirical patterns of known protein fragment-pair associations. As a result, the candidate poses that nanohedra generates for subsequent amino acid interface design appear highly native-like (at the protein backbone level), while simultaneously conforming to the exacting requirements for symmetry-based assembly. A retrospective computational analysis of successful vs failed experimental studies supports the expectation that this should improve the success rate for this challenging area of protein engineering.
Direction-sensitive dark matter search with the low-background gaseous detector NEWAGE-0.3b”
Authors: Ikeda Tomonori , Nakamura Kiseki , Shimada Takuya , Yakabe Ryota , Hashimoto Takashi , Ishiura Hirohisa , Nakamura Takuma , Ito Hiroshi , Ichimura Koichi , Abe Ko , Kobayashi Kazuyoshi , Tanimori Toru , Kubo Hidetoshi , Takada Atsushi , Sekiya Hiroyuki , Takeda Atsushi , Miuchi Kentaro
Published: April 2021

NEWAGE is a direction-sensitive dark matter search using a low-pressure gaseous time projection chamber. A low alpha-ray emission rate micro pixel chamber had been developed in order to reduce background for dark matter search. We conducted the dark matter search at the Kamioka Observatory in 2018. The total live time was 107.6 d, corresponding to an exposure of 1.1 kg$\>$d. Two events remained in the energy region of 50–60 keV, which was consistent with the expected background of 2.5 events. A directional analysis was carried out and no significant forward–backward asymmetry derived from the WIMP-nucleus elastic scatterings was found. Thus a 90$\%$ confidence level upper limit on the spin-dependent WIMP-proton cross-section of 50 pb for a WIMP mass of 100 GeV$\>c^{-2}$ was derived. This limit is the most stringent yet obtained from direction-sensitive dark matter search experiments.
Strategic Trading When Central Bank Intervention Is Predictable
Authors: Yang Liyan , Zhu Haoxiang
Published: April 2021

Market prices are noisy signals of economic fundamentals. In a two-period model, we show that if the central bank uses market prices as guidance for intervention, large strategic investors who benefit from high prices would depress market prices to induce a market-supportive intervention. Stronger anticipated interventions lead to deeper price depressions preintervention and sharper price reversals post-intervention. The central bank intervention harms strategic investors even though it is the investors who tried to mislead the central bank. The model predicts a V-shaped price pattern around central bank interventions, consistent with recent evidence. (JEL G14, G18)
Persuasive Action and Ideological Polarization in Congress
Authors: Vann Burrel
Published: April 2021

What drives polarized voting in Congress? This article develops a persuasive action model which argues that polarization in Congress depends on the assertive capacities of social movements, the vulnerability of political officials, and the partisanship of the environments they represent. Using multilevel analyses, I demonstrate that endorsements by the Tea Party movement influenced an increase in extreme (conservative) voting among legislators in the 112th Congress. These effects are strongest for vulnerable, freshman legislators representing amenable Republican contexts.
Debating the Law of Self-Determination of Gender Identity in Portugal: Composition and Dynamics of Advocacy Coalitions of Political and Civil Society Actors in the Discussion of Morality Issues
Authors: Mota Luís F , Fernandes Bruna
Published: April 2021

In the literature on morality issues, the most famous typology distinguishes countries from the “religious” and “secular” worlds, based on the presence or absence of partisan religious cleavages. Portugal belongs to the former world, yet in 2018, the Portuguese Parliament passed a law on the self-determination of gender identity. This article asks how such an outcome was possible, focusing on the role of political parties and civil society actors within advocacy coalitions. Our analysis reveals that, in addition to the role played by civil society actors, the “change coalition” won the dispute because it assembled a majority of votes in the parliament from left-wing progressive political parties. Moreover, actors from the “change coalition” developed a clear strategy of articulation before and during the debate. In contrast, the “blocking coalition,” composed of right-wing political parties and a few health-related actors, failed to define a coherent advocacy strategy.
Racial Injustice in Schools: Underscoring Social Work’s Obligation to Promote Antiracist Practice
Authors: Phillippo Kate L , Crutchfield Jandel
Published: April 2021

Children of color (COC) continue to have a range of disparate educational experiences that implicate structural and institutional racism as powerful, detrimental forces in P–12 schools. As members of a profession dedicated to empowerment and the dismantling of oppression, social workers are called to respond. Social workers work in and with schools in diverse roles (for example, as practitioners, community partners, organizational leaders, and contracted providers) and are ethically obligated to challenge injustice. This article—anchored in a framework focused on how race operates in schools and in the field of social work—considers the state of affairs for COC in schools, social work’s professional and ethical obligations, and extant opportunities for social workers to learn to address structural racism. The authors identify a gap between COC experiences and social work candidates’ preparation to respond, and therefore advocate for social work’s more explicit commitment to antiracist practice, research, and pedagogy. The authors share examples from within and beyond the field of social work that can guide next steps, anticipate challenges that would arise, and assert the importance of pursuing antiracism as a route toward meeting our profession’s ethical obligations. The article concludes with a discussion of implications for social work education, research, and practice.
Preparing for the new nursing licensure exam
Authors: Ignatavicius Donna D.
Published: April 2021

The National Council of State Boards of Nursing is changing its licensure exam to focus on a clinical judgment model. This article describes the current National Council Licensure Exam (NCLEX), the shift in focus from the nursing process to clinical judgment, and the intended emphasis of the next-generation NCLEX.
Does alarm fatigue start in nursing school?
Authors: Weeks Karen , Timalonis Joan , Donovan Laureen
Published: April 2021

Purpose:

Alarm fatigue among working nurses is a well-documented, high-priority safety issue. This article describes a study to learn whether alarm fatigue develops in undergraduate nursing student populations.

Methods:

This longitudinal quantitative study employed survey data from a single cohort of nursing students in the Southeastern US over a period of 18 months to assess nursing students' level of sensitivity to alarms, including the call bell, bathroom, fall and safety, I.V. infusion pumps, and telemetry alarms.

Results:

These data were significant for I.V. infusion pump alarms and indicated a general decrease in sensitivity over an 18-month period. Nursing students with previous healthcare experience also noted decreased sensitivity to bathroom call bells and fall and safety alarms.

Conclusion:

Alarm fatigue was recognized among the surveyed nursing students. Nurse educators also identified a performance-based strategy to increase student awareness of alarm fatigue and evidence-based strategies to minimize desensitization to alarms in both education and practice.
The Power of Place: Travel to Explore Structural Racism and Health Disparities
Authors: Marbin Jyothi , Lewis Leanna , Kuo Anda K. , Schudel Christine , Gutierrez Juan Raul
Published: April 2021

Problem

Dismantling structural racism is essential to achieving health equity, but there is little guidance for medical educators who wish to teach learners to recognize and confront structural racism.

Approach

Critical consciousness provides a framework to identify and dismantle structural racism. Using a critical consciousness approach, the authors developed a novel 5-day travel experience to the American South for medical residents and faculty to explore the history and legacy of structural racism and the Civil Rights Movement. The purpose of the travel was to examine the connection between structural racism, especially anti-Black racism, and health disparities to better address health inequities within the participants’ own home environment. Throughout the trip, faculty leaders applied principles of cultural humility and techniques from critical pedagogy, including recognizing the value of everyone in the room, creating cognitive disequilibrium, and promoting authentic dialogue.

Outcomes

End-of-week surveys revealed that the trip was well received. Organizers learned important lessons related to faculty and resident dynamics, race-based affinity group meetings, and the respectful use of stories as a tool for learning. Post-trip surveys at 1, 6, and 12 months revealed 3 major themes: participants experienced (1) transformed understanding of systemic racism, (2) increased motivation and bravery to act when witnessing interpersonal and structural racism, and (3) increased practice of cultural humility.

Next Steps

Cultural humility and critical pedagogy can be used with travel to support learners in recognizing and confronting structural racism. The application of such techniques should be explored in local learning environments to foster commitment and action toward dismantling structural racism. In teaching structural racism, medical educators must be willing to consider new ways of teaching and learning.
Hands Off Yet All In: A Virtual Clerkship Pilot in the Ambulatory Setting During the COVID-19 Pandemic
Authors: Rydel Tracy A. , Bajra Rika , Schillinger Erika
Published: April 2021

Problem

There is a paucity of guidance regarding implementation of telemedicine curricula at the clerkship level, particularly with students actively engaged in video and telephone encounters. The COVID-19 pandemic caused rapid shifts in the delivery of medical education to clerkship-level students. This article describes the successful pilot of a direct patient care, virtual health curriculum at the clerkship level and discusses lessons learned.

Approach

All 18 preceptors and 5 students at Stanford University School of Medicine, California, enrolled in the required 4-week family medicine clerkship in April 2020 were connected as virtual partners via a commercial video platform. The combined use of both this video program and Epic electronic health record (EHR) software as modes for teaching and patient care led to technical challenges and logistical hurdles. As part of an iterative process, clerkship leadership identified problems via preceptor and student interviews and integrated that feedback to create a model for delivering high-quality, clerkship-level clinical instruction during the COVID-19 shelter in place order.

Outcomes

Of those who completed an evaluation, the majority of preceptors (n = 16; 89%) and students (n = 4; 100%, 1 student did not respond) expressed satisfaction with the virtual, remote teaching model conducted over 37 clinic visits. A detailed 14-step process list resulted from identifying and addressing both audio and video technical challenges and is provided for use by other institutions that wish to implement this workflow.

Next Steps

Future directions include assessing patient perspectives on the involvement of students in virtual visits, soliciting patient input for a more robust patient–physician–student virtual experience, and integrating a multiparty platform, when available, via the EHR to afford greater student autonomy.
Some effects of putative G-protein biased mu-opioid receptor agonists in male rhesus monkeys
Authors: Cornelissen Jeremy C. , Blough Bruce E. , Bohn Laura M. , Negus S. Stevens , Banks Matthew L.
Published: April 2021

G-protein-biased mu-opioid receptor (GPB-MOR) agonists are an emerging class of compounds being evaluated as candidate analgesics and agonist medications for opioid use disorder. Most of the basic pharmacology of GPB-MOR agonists has been conducted in rodents and much less is known how the basic behavioral pharmacology of these compounds translates to nonhuman primates. The present study determined the antinociceptive potency and time course of three putative GPB-MOR agonists: (+)-oliceridine (i.e. TRV130), SR14968, and SR17018 in male rhesus monkeys (n = 3). In addition, the respiratory effects of these compounds were also indirectly determined using a pulse oximeter to measure percent peripheral oxygen saturation (%SpO2). The largest intramuscular oliceridine dose (3.2 mg/kg) produced significant antinociception at 50°C, but not 54°C, and peak effects were between 10 and 30 min. Oliceridine also decreased SpO2 below the 90% threshold that would be clinically categorized as hypoxia in two out of three monkeys. The largest intramuscular SR14968 dose (0.32 mg/kg) produced 100% MPE at 50°C, but not 54°C, in two out of three monkeys, and peak effects were between 30 and 100 min. The largest intravenous SR17018 dose (1 mg/kg) produced 100% MPE at 50°C, but not 54°C, in the same two out of three monkeys, and peak effects were between 30 and 100 min. Solubility limitations for both SR14968 and SR17018 impaired our ability to determine in-vivo potency and effectiveness on antinociceptive and %SpO2 measures for these two compounds.
Facial Defect Repair Using a Flap Based on the Superficial Temporal Artery
Authors: Liu Anjun , Su Xianlin , Jiao Yang , Yang Ping , Dai Damao , Xu Jianyang
Published: April 2021

Background:

Although a local flap repair is optimal for facial defects, an extra flap or split-thickness skin graft may be needed if a sufficient local flap area is not available. In this study, we developed a distant axial pedicle flap procedure based on the inner transverse perforator of the ascending frontal branch of the superficial temporal artery to repair facial defects while meeting patients’ requirements for a like-for-like tissue reconstructive outcome.

Methods:

For defect repair after facial tumor removal, we designed upper frontal facial pedicle flaps based on the inner transverse perforator of the ascending frontal branch of the superficial temporal artery. Facelift procedures were applied concomitantly for donor site repair.

Results:

We applied the procedure to 12 patients who underwent curative lesion resection. Notably, all flaps survived. Venous congestion developed in only 1 case, in which the wound was covered with heparin sodium gauze to inhibit wound coagulation until the congestion gradually resolved. In all cases, the frontal donor site scars were adjacent to the hairline and were concealed very well by hair growth. During postoperative follow-ups of 8–43 months, the patients experienced only minor complications.

Conclusions:

The flap based on the inner transverse perforator of the ascending frontal branch of the superficial temporal artery is a useful alternative for facial defect repair surgery. The low incidence of complications and easy concealment of the donor site underscore the safe and aesthetically acceptable nature of the procedure.
Upper Respiratory Tract Co-detection of Human Endemic Coronaviruses and High-density Pneumococcus Associated With Increased Severity Among HIV-Uninfected Children Under 5 Years Old in the PERCH Study
Authors: Park Daniel E. , Higdon Melissa M. , Prosperi Christine , Baggett Henry C. , Brooks W. Abdullah , Feikin Daniel R. , Hammitt Laura L. , Howie Steve R. C. , Kotloff Karen L. , Levine Orin S. , Madhi Shabir A. , Murdoch David R. , O’Brien Katherine L. , Scott J. Anthony G. , Thea Donald M. , Antonio Martin , Awori Juliet O. , Baillie Vicky L. , Bunthi Charatdao , Kwenda Geoffrey , Mackenzie Grant A. , Moore David P. , Morpeth Susan C. , Mwananyanda Lawrence , Paveenkittiporn Wantana , Ziaur Rahman Mohammed , Rahman Mustafizur , Rhodes Julia , Sow Samba O. , Tapia Milagritos D. , Deloria Knoll Maria
Published: April 2021

Background:

Severity of viral respiratory illnesses can be increased with bacterial coinfection and can vary by sex, but influence of coinfection and sex on human endemic coronavirus (CoV) species, which generally cause mild to moderate respiratory illness, is unknown. We evaluated CoV and pneumococcal co-detection by sex in childhood pneumonia.

Methods:

In the 2011–2014 Pneumonia Etiology Research for Child Health study, nasopharyngeal and oropharyngeal (NP/OP) swabs and other samples were collected from 3981 children <5 years hospitalized with severe or very severe pneumonia in 7 countries. Severity by NP/OP detection status of CoV (NL63, 229E, OC43 or HKU1) and high-density (≥6.9 log10 copies/mL) pneumococcus (HDSpn) by real-time polymerase chain reaction was assessed by sex using logistic regression adjusted for age and site.

Results:

There were 43 (1.1%) CoV+/HDSpn+, 247 CoV+/HDSpn−, 449 CoV−/HDSpn+ and 3149 CoV−/HDSpn− cases with no significant difference in co-detection frequency by sex (range 51.2%–64.0% male, P = 0.06). More CoV+/HDSpn+ pneumonia was very severe compared with other groups for both males (13/22, 59.1% versus range 29.1%–34.7%, P = 0.04) and females (10/21, 47.6% versus 32.5%–43.5%, P = 0.009), but only male CoV+/HDSpn+ required supplemental oxygen more frequently (45.0% versus 20.6%–28.6%, P < 0.001) and had higher mortality (35.0% versus 5.3%–7.1%, P = 0.004) than other groups. For females with CoV+/HDSpn+, supplemental oxygen was 25.0% versus 24.8%–33.3% (P = 0.58) and mortality was 10.0% versus 9.2%–12.9% (P = 0.69).

Conclusions:

Co-detection of endemic CoV and HDSpn was rare in children hospitalized with pneumonia, but associated with higher severity and mortality in males. Findings may warrant investigation of differences in severity by sex with co-detection of HDSpn and SARS-CoV-2.
Chronic Exertional Compartment Syndrome Caused by Functional Venous Outflow Obstruction
Authors: McGinley Joseph C. , Thompson Trey A. , Ficken Shawn , White Jessica
Published: April 2021

Objective:

Investigate the theory that chronic exertional compartment syndrome (CECS) results from venous outflow obstruction due to functional muscular compression. Chronic exertional compartment syndrome occurs when increased pressure within a muscle compartment produces pain and/or neurologic symptoms. The exact etiology of CECS is unknown, leading to inconsistent diagnostic and treatment plans.

Study Design:

Retrospective case series.

Setting:

Private practice and sports medicine.

Patients:

Two hundred eighty-four patients with exercise-induced lower leg pain. Twenty-two patients lost to follow-up.

Interventions:

Leg vasculature was evaluated using stress computed tomography angiography (CTA) and MVP Flex to identify areas of functional venous compression. All patients then underwent targeted botulinum toxin treatment. Posttreatment follow-up imaging was performed using stress CTA in 197 patients.

Main Outcome Measures:

Presence of functional venous compression on stress CTA. Symptom reduction and normalization of venous flow after targeted botulinum toxin injections.

Results:

Baseline imaging demonstrated CECS and functional venous obstruction with replication of symptoms in 260 of 284 patients [91.5% ± 3.2% (95% CI)]. Four weeks after treatment, 227 of 284 patients [79.9% ± 4.7% (95% CI)] described reduced/resolved symptoms with activity. One hundred fifty-five of the 197 patients [78.7% ± 5.7% (95% CI)] reimaged with stress CTA demonstrated resolved/reduced venous outflow obstruction. Twenty-two patients were lost to follow-up, and 35 patients had persistent symptoms.

Conclusion:

Chronic exertional compartment syndrome results from venous outflow obstruction due to functional muscular compression. Understanding the cause of CECS will allow the development of more precise and successful treatment plans. Based on our findings, treatment should be directed at the sites of venous compression.
Genetic architecture of type 2 diabetes and its shared genetic component with low birth weight in African Americans
Authors: Ruiz-Narváez Edward A.
Published: April 2021

Purpose of review

Recent large-scale multiancestry efforts has contributed to our knowledge of the hereditary basis of type 2 diabetes (T2D). The present review will summarize findings of the genetic basis of T2D in African Americans, a population group with a disproportionate burden of this disease.

Recent findings

To date, >400 risk genetic variants have been found to be associated with the risk of T2D across populations of different ancestries. Although these findings are based on primarily European-ancestry populations, most of the identified loci show similar associations in African Americans. Ancestry-specific analyses including genome-wide associations studies (GWAS) in African Americans, Africans; as well as admixture mapping scans in African Americans have identified additional risk variants and genomic loci associate with the risk of T2D. These efforts have also uncovered new genetic links between low birth weight and T2D. In particular, admixture mapping approaches have identified a shared genetic ancestry component of both phenotypic traits in African Americans.

Recent findings have helped us to better understand the genetic basis of T2D in African Americans. Of particular interest are new genetic discoveries linking low birth weight and T2D, two conditions with a much higher prevalence in African Americans compared to U.S. whites. Continuing work, including large-scale sequencing efforts would add to our knowledge of the genetic architecture of T2D in African Americans, as well as genetic links with other conditions.
Desensitization and management of allograft rejection
Authors: Zaffiri Lorenzo
Published: April 2021

Purpose of review

Chronic lung allograft dysfunction (CLAD) limits the success of lung transplantation. Among the risk factors associated with CLAD, we recognize pretransplant circulating antibodies against the human leukocyte antigens (HLA), acute cellular rejection (ACR) and antibody-mediated rejection (AMR). This review will summarize current data surrounding management of desensitization, ACR, AMR, and CLAD.

Recent findings

Strategies in managing in highly sensitized patients waiting for lung transplant include avoidance of specific HLA antigens and reduction of circulating anti-HLA antibodies at time of transplant. Several multimodal approaches have been studied in the treatment of AMR with a goal to clear circulating donor-specific antibodies (DSAs) and to halt the production of new antibodies. Different immunosuppressive strategies focus on influence of the host immune system, particularly T-cell responses, in order to prevent ACR and the progression of CLAD.

The lack of significant evidence and consensus limits to draw conclusion regarding the impact of specific immunosuppressive regimens in the management of HLA antibodies, ACR, and CLAD. Development of novel therapeutic agents and use of multicenter randomized clinical trials will allow to better define patient-specific treatments and improve the length and quality of life of lung transplant recipients.
Feasibility of a Pilot Home Phlebotomy Program for Pediatric Hematology/Oncology Patients During the COVID-19 Pandemic
Authors: Sisler India , Cohen Debra , Skinner Lee Ann , Aiken Crystal , Laver Joseph
Published: April 2021

Medical care during the Coronavirus 2019 global pandemic required significant shifts in health care delivery systems. Telehealth was widely deployed but was of limited utility for patient populations who rely heavily on laboratory monitoring. This includes pediatric hematology and oncology patients. We report on the feasibility and successful implementation of a home phlebotomy program that has minimized disruption in care for this high-risk patient population. During the initial months of the COVID-19 outbreak, we completed 189 home phlebotomy visits for pediatric hematology and oncology patients. Patient and staff satisfaction with the program were high, and potential exposures to COVID were avoided.
Validation of a Questionnaire to Identify Respiratory Tract Infections in Children With Sickle Cell Disease
Authors: De Aliva , Anekwe Chika V. , Kattan Meyer , Yao Yujing , Jin Zhezhen , Brittenham Gary M. , Lee Margaret T.
Published: April 2021

Background:

No validated questionnaires have been published that are specific for identifying respiratory infections in children with sickle cell disease (SCD).

Methods:

A questionnaire was developed that included 6 respiratory symptoms (difficulty breathing, wheezing, fever, cough, runny or stuffy nose, and sore throat) to identify respiratory events for a clinical trial. The questionnaire results were compared with identification of viral respiratory pathogens from nasal samples by reverse transcriptase polymerase chain reaction.

Results:

Eighty questionnaire responses (40 with symptom/s and 40 without) paired with isolation of viral respiratory pathogen from nasal samples were obtained from 53 children with SCD, ages 4 to 18 years over 2 separate periods in different seasons. The questionnaire yielded a sensitivity of 82%, specificity of 72% with an overall accuracy of 76%. The kappa value was 0.53, indicating moderate agreement, and the Fleiss’ kappa test statistic was 4.77 with P<0.001, indicating that agreement between the 2 methods was not by chance.

Conclusion:

These results provide evidence for validity of this 6-symptom respiratory questionnaire in identification of respiratory viral infections for use in SCD-related research.
Two Cases of Veno-occlusive Disease/Sinusoidal Obstruction Syndrome After Thioguanine Treatment for Acute Lymphoblastic Leukemia
Authors: Gruhn Bernd , Brodt Grit , Mentzel Hans-Joachim , Ernst Jana
Published: April 2021

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of hematopoietic cell transplantation conditioning or high-dose chemotherapy. The underlying pathogenesis involves toxic injury to hepatocytes and sinusoidal endothelial cells. Presenting symptoms include ascites, weight gain, hepatomegaly, and hyperbilirubinemia. Severe VOD/SOS with multiorgan failure has a mortality rate of >80% if left untreated. Thioguanine, a chemotherapy drug used to treat acute lymphoblastic leukemia, has been shown to cause VOD/SOS. Here, we describe cases of 2 patients who developed very severe VOD/SOS after starting thioguanine for acute lymphoblastic leukemia; both achieved complete remission with defibrotide and experienced no defibrotide-related adverse events.
Factors Associated With Quality of Life Among People Living With a Stoma in Nonmetropolitan Areas
Authors: Ketterer Sarah N. , Leach Michael J. , Fraser Caitlin
Published: April 2021

Background

Interruption of gastrointestinal continuity through surgical formation of a stoma can be lifesaving. However, it is also typically associated with reduced quality of life (QoL). Although past research has investigated QoL among people living with a stoma, no known studies have investigated stoma-related QoL, specifically among nonmetropolitan residents who may experience distinct health issues compared with their metropolitan counterparts.

Objectives

The aim of the study was to investigate the level of and factors associated with QoL among people living with a stoma in nonmetropolitan Australia.

Methods

In a cross-sectional survey, 678 adults with colostomy, ileostomy, and/or urostomy and with membership in a regional Victorian stoma association were given the City of Hope Quality of Life Questionnaire for a Patient With an Ostomy (QOL-O). Total QoL score was calculated and described before categorization into quintiles. Patient factors associated with quintiles of QoL were assessed using univariable and multivariable proportional odds ordinal logistic regression, with a 95% confidence interval excluding 1.00 denoting statistical significance.

Results

Overall, 311 regional ostomy association members (46%) responded to any QOL-O questions; 285 members responded to >80% of QOL-O questions and contributed data to the study. Their median age was 73 years, and 60% were male. The median total QoL score was 6.9 on a scale of 0–10, where a higher number indicates better QoL. Factors independently associated with better QoL in the multivariable model were working full/part time, no poststoma clothing change, poststoma sexual activity, and older age. Factors independently associated with worse QoL were poststoma depression and a stoma location issue.

Discussion

People living with a stoma in nonmetropolitan Australia reported moderate-to-high QoL. Better QoL was identified in those who worked, had no poststoma clothing change, were sexually active poststoma, and were older. Worse QoL was seen in those who had poststoma depression and stoma location issues. Healthcare providers could influence stoma-related QoL by identifying risk factors and tailoring interventions toward individuals in nonmetropolitan settings.
Circadian Rhythms in Sudden Cardiac Arrest
Authors: Tran Dieu-My T. , St. Pierre Schneider Barbara , McGinnis Graham R.
Published: April 2021

Background

Sudden cardiac arrest (SCA) is a serious public health issue caused by the cessation of cardiac electrical and mechanical activity. Despite advances in pedestrian lifesaving technologies like defibrillators, the SCA mortality rate remains high, and survivors are at risk of suffering ischemic injury to various organs. Understanding the contributing factors for SCA is essential for improving morbidity and mortality. One factor capable of influencing SCA incidence and survival is the time of day at which SCA occurs.

Objectives

This review focused on the effect of time of day on SCA incidence, survival rate, and survival to discharge over the past 30 years and the role of age, sex, and SCA location in modulating the timing of SCA.

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews criteria guided this review. Four databases (PubMed, Cochrane Libraries, Scopus, and Cumulative Index to Nursing and Allied Health Literature) were queried for research reports or articles addressing time of day and cardiac arrest, which were subsequently screened by the authors for inclusion in this analysis.

Results

A total of 48 articles were included in the final analysis. This analysis showed a bimodal SCA distribution with a primary peak in the morning and a secondary peak in the afternoon; these peaks were dependent on age (older persons), sex (more frequent in males), and the location of occurrence (out-of-hospital cardiac arrest vs. in-hospital cardiac rest). Survival following SCA was lowest between midnight and 06:00 a.m.

Discussion

The circadian rhythm likely plays an important role in the time-of-day-dependent pattern that is evident in both the incidence of and survival following SCA. There is a renewed call for nursing research to examine or address circadian rhythm as an element in studies involving older adults and activities affecting cardiovascular or respiratory parameters.
Improving Poor Outcomes of Children With Biliary Atresia in South Africa by Early Referral to Centralized Units
Authors: van der Schyff Francisca , Terblanche Alberta J. , Botha Jean F.
Published: April 2021

Objectives:

Biliary atresia (BA) is a progressive fibrosing cholangiopathy of infancy, the most common cause of cholestatic jaundice in infants and the top indication for liver transplantation in children. Kasai portoenterostomy (KPE) when successful may delay the requirement for liver transplantation, which in the majority offers the only cure. Good outcomes demand early surgical intervention, appropriate management of liver cirrhosis, and in most cases, liver transplantation. These parameters were audited of children with BA treated at the Steve Biko Academic Hospital (SBAH) in Pretoria, South Africa.

Methods:

All children with BA who were managed at SBAH between June 2007 and July 2018 were included. Parameters measured centered on patient demographics, timing of referral and surgical intervention, immediate and long-term outcomes of surgery, and follow-up management.

Results:

Of 104 children treated, 94 (90%) were KPE naive. Only 23/86 (26%) of children were referred before 60 days of life and 42/86 (49%) after 120 days. Median time to surgical assessment and surgery was 4 (IQR 1–70) and 5 (IQR 1–27) days post presentation, respectively. The median age at KPE was 91 days (IQR 28–165), with only 4/41 (12%) of KPEs performed before 60 days of life. Of those with recorded outcomes, 12/33 (36%) achieved resolution of jaundice. Only a third of the cohort were referred for transplantation.

Conclusion:

Children with BA have poor outcomes in the public health sector in South Africa. Late referrals, delayed diagnostics, advanced age at KPE with low drainage rates, poor follow–up, and low transplant rates account for low survival. Early referral to units offering expert intervention at all stages of care, including transplantation, would offer the best outcomes.