bluuebunny/crossref_metadata_2025_split huggingface dataset:
pRB-Depleted Pluripotent Stem Cell Retinal Organoids Recapitulate Cell State Transitions of Retinoblastoma Development and Suggest an Important Role for pRB in Retinal Cell Differentiation
Authors: Rozanska Agata , Cerna-Chavez Rodrigo , Queen Rachel , Collin Joseph , Zerti Darin , Dorgau Birthe , Beh Chia Shyan , Davey Tracey , Coxhead Jonathan , Hussain Rafiqul , Al-Aama Jumana , Steel David H , Benvenisty Nissim , Armstrong Lyle , Parulekar Manoj , Lako Majlinda 
Published: January 2022

AbstractRetinoblastoma (Rb) is a childhood cancer of the developing retina, accounting for up to 17% of all tumors in infancy. To gain insights into the transcriptional events of cell state transitions during Rb development, we established 2 disease models via retinal organoid differentiation of a pRB (retinoblastoma protein)-depleted human embryonic stem cell line (RB1-null hESCs) and a pRB patient-specific induced pluripotent (iPSC) line harboring a RB1 biallelic mutation (c.2082delC). Both models were characterized by pRB depletion and accumulation of retinal progenitor cells at the expense of amacrine, horizontal and retinal ganglion cells, which suggests an important role for pRB in differentiation of these cell lineages. Importantly, a significant increase in the fraction of proliferating cone precursors (RXRγ+Ki67+) was observed in both pRB-depleted organoid models, which were defined as Rb-like clusters by single-cell RNA-Seq analysis. The pRB-depleted retinal organoids displayed similar features to Rb tumors, including mitochondrial cristae aberrations and rosette-like structures, and were able to undergo cell growth in an anchorage-independent manner, indicative of cell transformation in vitro. In both models, the Rb cones expressed retinal ganglion and horizontal cell markers, a novel finding, which could help to better characterize these tumors with possible therapeutic implications. Application of Melphalan, Topotecan, and TW-37 led to a significant reduction in the fraction of Rb proliferating cone precursors, validating the suitability of these in vitro models for testing novel therapeutics for Rb.
Development of synthetic biotics as treatment for human diseases
Authors: Brennan Aoife M 
Published: January 2022

Abstract
Advances in synthetic biology have allowed the generation of strains of bacteria that are genetically altered to have specific therapeutic benefits. These synthetic biotics, also widely referred to as engineered living therapeutics, have tremendous potential as a new therapeutic modality, and several have advanced into the clinic and human testing. This review outlines some of the unique attributes of synthetic biotics as well as some of the challenges in their development as prescription products. Regulatory considerations are discussed, and a case study of a program that has advanced into Phase 2 testing is provided: SYNB1618 for the treatment of PKU.
The Role of the Artery of Ligamentum Teres in Revascularization in Legg-Calve-Perthes Disease
Authors: Morris William Z. , Valencia Angel A. , McGuire Molly F. , Kim Harry K.W. 
Published: January 2022

Introduction:
A recent cadaveric study supported that most immature hips are supplied by the artery of ligamentum teres and suggested this medial vascular source may influence the pattern of revascularization in Legg-Calve-Perthes disease (LCPD). The purposes of this study were to characterize the perfusion pattern of the capital femoral epiphysis and determine the role of the artery of ligamentum teres in early revascularization of LCPD.

Methods:
Retrospective review of perfusion magnetic resonance imaging (pMRI) from 64 hips in early stage LCPD (Waldenström stage I to IIa) was performed. Two independent graders categorized perfusion pattern based on the presence of perfusion medially (from artery of ligamentum teres) and/or laterally (from the medial femoral circumflex artery) on coronal and sagittal MRI series: type 1—lateral perfusion only, type 2—separate medial and lateral perfusion, or type 3—coalescent medial and lateral perfusion. Lateral pillar classification was obtained for hips that reached mid-fragmentation.

Results:
We identified 64 patients (75% male) with mean age at diagnosis of 8.5±2.1 years. 36% (23/64) hips underwent pMRI during stage I and 64% (41/64) during stage IIa. pMRI revealed separate and distinct medial and lateral sources of perfusion (type 2) in 50% (32/64) hips. In stage I, the distribution of type 1/2/3 hips was found to be 26%/52%/22%. However, in stage IIa there was a nonsignificant trend toward greater coalescence of the medial and lateral perfusion with a distribution of type 1/2/3 of 7%/49%/44% (P=0.07). There was a nonsignificant trend toward weak negative linear correlation between lower initial perfusion grade and worsened lateral pillar classification at mid-fragmentation (r=−0.25, P=0.05).

Conclusion:
The presence of separate and distinct areas of perfusion of medial and lateral capital femoral epiphysis provides further evidence of the role of the ligamentum teres vessels in revascularization during the early stages of LCPD. The changes in perfusion pattern with disease progression likely reflect that medial femoral circumflex artery and ligamentum teres vessel revascularization occur separately, but ultimately coalesce posteriorly over time.

Level of Evidence:
Level II—prognostic study.
Stem cells to reverse aging
Authors: Chang Le , Fan Weiwen , Pan Xinghua , Zhu Xiangqing 
Published: January 2022

Abstract
As human life expectancy continues to increase and the birth rate continues to decline, the phenomenon of aging is becoming more prominent worldwide. Therefore, addressing the problems associated with global aging has become a current research focus. The main manifestations of human aging are structural degeneration and functional decline of aging tissues and organs, quality of life decline, decreased ability to resist diseases, and high incidence rates of a variety of senile degenerative diseases. Thus far, no ideal treatments have been found. Stem cell (SC) therapies have broad application prospects in the field of regenerative medicine due to the inherent biological characteristics of SCs, such as their plasticity, self-renewal, and multidirectional differentiation potential. Thus, SCs could delay or even reverse aging. This manuscript reviews the causes of human aging, the biological characteristics of SCs, and research progress on age reversal.
Respective Impact of Day and Night Bed Baths on Critical Care Patients
Authors: Bernard Mélanie , Godard Baptiste , Camara Corika , Gaultier Alexandra , Hudry Cédric , Marlot Thibault , Sergent Jérémy , Coadic Delphine , David Vanessa , Damoisel Charles , Sztrymf Benjamin ,   The ToNu investigators
Published: January 2022

Background
Despite data supporting the reduction of interactions with patients during nighttime, bed bathing is sometimes performed within this period in sedated patients unable to manage their own hygiene care.

Objectives
To compare patient physiologic variables and adverse effect incidence between night and day bed baths.

Methods
This was a single-center prospective observational study in a 12-bed intensive care unit during 2 months. Night period was defined to run from 10 pm to 6 am. Night bed baths were provided to sedated ventilated patients whatever their sedation, if their Richmond Agitation Sedation Scale score was −2 or deeper. Bed bath–induced changes in physiological variables, treatments, and related unscheduled events were registered during both night and day bed baths.

Results
Twenty-one patients (aged 62.9 [52.5-73.2] years, 14 male patients) were included. We registered 97 night bed baths and 95 day bed baths. Heart rate increased only after day bed baths (85 beats/min [bpm] [69-97 bpm] vs 88 bpm [73-98 bpm], P = .02). Increase in Richmond Agitation Sedation Scale score occurred, respectively, during 13 (13.4%) and 8 (8.4%) night and day bed baths, without significant differences. Body temperature significantly decreased during both night and day bed baths (respectively, 37°C [36.6°C-37.4°C] vs 36.6°C [36.2°C-37.2°C], P < .0001; and 36.9°C [36.5°C-37.2°C] vs 36.7°C [36.2°C-37.2°C], P = .0006). Overall, unscheduled events, whether physiologic changes, pain, or calling a physician in rescue occurred in 97 procedures (50.5%), irrespective of their timing (night vs day, respectively 53% [54.6%] vs 44% [46.3%], P = .31).

Discussion
Although unscheduled events occurred in half of bed baths, differences evidenced between nighttime and daytime bed baths were scarce. The appropriateness of nighttime bed bathing remains questionable.
Thirst Interventions in Adult Acute Care—What Are the Recommended Management Options and How Effective Are They?
Authors: Clark Jenny , Archer Sally K. 
Published: January 2022

Purpose
The aim of this study was to review the scope and quality of evidence for thirst treatment in adult acute care.

Methods
A systematic review was completed by 2 independent reviewers using MEDLINE, PubMed, BNI, EMBASE, EMCARE, and CINAHL databases and additional hand searching in June 2020. Interventions to relieve thirst for inpatients receiving acute care were included. Evidence was appraised against the levels of evidence for therapeutic studies, and a risk-of-bias assessment was completed for included studies. Outcomes are presented via narrative synthesis. Meta-analysis was planned.

Results
Four studies (out of 844) were eligible reporting thirst outcomes from 611 critical care patients. Meta-analysis could not be completed because a priori criteria were not met. Two randomized controlled trials represented the highest level of evidence. Thirst assessment was completed via a self-reported scale in all reviewed works. Interventions included cold water sprays or swabs, menthol lip moisturizer, and use of humidification. Three works demonstrate reduced thirst scores; all interventions in these studies exploit cooling effects to the oropharynx with the aim of preabsorptive satiation of thirst. A humidified oxygen circuit showed a neutral response when compared with a nonhumidified circuit.

Conclusions
There is a limited but growing evidence base related to thirst treatment in the acute setting. Studies using a “bundle” of topical interventions incorporating cooling and menthol treatments showed positive effects in reducing symptom burden. Work to explore the scope of application for thirst treatment for patients unable to self-report, consideration of sustained effects, and a study of individual versus combined effects of bundle elements would be welcomed as the evidence base continues to develop.
Massachusetts Intensive Care Unit Nurses From Multiple Hospitals Develop a Collaborative to Improve Delirium Assessment Accuracy
Authors: O'Donoghue Sharon C. , Meyers Karen , Manning Cathie R. , Pellegrino Linda S. , Ryan Colleen P. , Crowell Amanda M. , Nolan Lisa M. , Gallagher Gail E. 
Published: January 2022

Background and Relevance
Early recognition of delirium mobilizes nurses to intervene in a timely manner to minimize cognitive, physical, and mental health burdens. The life-altering challenges of unrecognized delirium in intensive care unit (ICU) patients motivated a group of Massachusetts ICU nurse leaders to form a collaborative and improve delirium screening accuracy in 4 area hospitals.

Local Problem
Baseline audits confirmed a lack of delirium screening accuracy across multiple institutions. The purpose of this article is to describe how our collaborative was developed and to outline our delirium accuracy assessment program.

Methods
In March of 2015, 2 graduates from the Clinical Scene Investigator Academy contacted members within the Boston cohort to form a regional collaborative to improve patient outcomes. The purpose of our project was to improve our delirium assessment accuracy to greater than 80% in patients across our ICUs. Using a successful project, we scaled this work based on the needs of each institution. A preaudit-postaudit design was used to evaluate the effectiveness of our programs.

Results
Data showed an improved overall accuracy assessment of 88.3% (P < .01), whereas the patients with an altered Richmond Agitation Sedation Scale markedly improved to 87.7% (P < .01).

Conclusions
Every ICU in the United States is working on improving reportable quality metrics, but all too often, this work is being done in silos. When critical care nurses have the knowledge, skills, and time to work together, they can begin to transform health care.
Prenatal exposure to metal mixtures and newborn neurobehavior in the Rhode Island Child Health Study
Authors: Tung Pei Wen , Burt Amber , Karagas Margaret , Jackson Brian P. , Punshon Tracy , Lester Barry , Marsit Carmen J. 
Published: January 2022

Background:
Prenatal exposure to metals can affect the developing fetus and negatively impact neurobehavior. The associations between individual metals and neurodevelopment have been examined, but little work has explored the potentially detrimental neurodevelopmental outcomes associated with the combined impact of coexisting metals. The objective of this study is to evaluate prenatal metal exposure mixtures in the placenta to elucidate the link between their combined effects on newborn neurobehavior.

Method:
This study included 192 infants with available placental metal and NICU Network Neurobehavioral Scale data at 24 hours–72 hours age. Eight essential and nonessential metals (cadmium, cobalt, copper, iron, manganese, molybdenum, selenium, zinc) detected in more than 80% of samples were tested for associations with atypical neurobehavior indicated by NICU Network Neurobehavioral Scale using logistic regression and in a quantile g-computation analysis to evaluate the joint association between placental metal mixture and neurobehavioral profiles.

Results:
Individually, a doubling of placental cadmium concentrations was associated with an increased likelihood of being in the atypical neurobehavioral profile (OR = 2.39; 95% CI = 1.05 to 5.71). In the mixture analysis, joint effects of a quartile increase in exposure to all metals was associated with 3-fold increased odds of newborns being assigned to the atypical profile (OR = 3.23; 95% CI = 0.92 to 11.36), with cadmium having the largest weight in the mixture effect.

Conclusions:
Prenatal exposure to relatively low levels of a mixture of placental metals was associated with adverse newborn neurobehavior. Examining prenatal metal exposures as a mixture is important for understanding the harmful effects of concomitant exposures in the vulnerable populations.
A Real-world Claims Data Analysis of Meningococcal Serogroup B Vaccine Series Completion and Potential Missed Opportunities in the United States
Authors: Packnett Elizabeth R. , Zimmerman Nicole M. , Kim Gilwan , Novy Patricia , Morgan Laura C. , Chime Nnenna , Ghaswalla Parinaz 
Published: January 2022

Background:
In the United States, meningococcal serogroup B (MenB) vaccination is recommended for 16–23-year-olds based on shared clinical decision-making. We estimated series completion among individuals initiating MenB vaccination for the 2 available vaccines: MenB 4-component (MenB-4C, doses at 0 and ≥1 month) and MenB factor H binding protein (MenB-FHbp, doses at 0 and 6 months).

Methods:
This retrospective health insurance claims data analysis included 16–23-year-olds who initiated MenB vaccination (index date) during January 2017 to November 2018 (MarketScan Commercial Claims and Encounters Database) or January 2017 to September 2018 (MarketScan Multi-State Medicaid Database) and had continuous enrollment for ≥6 months before and ≥15 months after index. The main outcome was MenB vaccine series completion within 15 months. Among noncompleters, preventive care/well-child and vaccine administrative office visits were identified as potential missed opportunities for series completion. Robust Poisson regression models identified independent predictors of series completion.

Results:
In the Commercial (n = 156,080) and Medicaid (n = 57,082) populations, series completion was 56.7% and 44.7%, respectively, and was higher among those who initiated MenB-4C versus MenB-FHbp (61.1% versus 49.8% and 47.8% versus 33.9%, respectively; both P < 0.001). Among noncompleters, 40.2% and 34.7% of the Commercial and Medicaid populations, respectively, had ≥1 missed opportunity for series completion. Receipt of MenB-4C and younger age were independently associated with a higher probability of series completion.

Conclusions:
Series completion rates were suboptimal but were higher among those who initiated MenB-4C. To maximize the benefits of MenB vaccination, interventions to improve completion and reduce missed opportunities should be implemented.
Evaluation of Biomechanical Effects and Patient Benefits of a New Orthotic Ankle Joint in Stance Control Orthosis Fittings
Authors: Schmalz Thomas , Köhler Thomas Maximilian , Burkhardt Katharina , Dlugoszek Annika , Overdevest Etienne , Kannenberg Andreas , Bellmann Malte 
Published: January 2022

ABSTRACT

Introduction
A newly introduced generation of orthotic ankle joints with adjustable dorsiflexion and plantarflexion resistances and increased range of motion (ROM) has been well established in orthotic fittings of neurological patients with ankle foot orthoses. The aim of the present study was to investigate whether users of stance control orthoses (SCOs) may also benefit from this orthotic ankle joint principle using a biomechanical test design.

Methods
Six patients unilaterally fitted with an SCO (E-MAG Active) with the orthotic ankle joint NexGearTango (NGT; Ottobock, Duderstadt, Germany), an ankle joint representing the new principle, were enrolled in the study. The modular principle of the ankle joint allowed testing both the new functionality and the characteristics of a conventional orthotic ankle joint (CAJ; limited uncontrolled ROM). Level walking at slow, medium, and fast speed and with given short steps, ascending and descending a ramp with 10° inclination and standing (level ground as well as 10° incline and decline standing), were assessed while using NGT or CAJ, respectively. Kinematic and kinetic data were captured with an optoelectronic camera system and two force plates.

Results
The reliability of switching from stance to swing of the orthotic knee joint was clearly enhanced with NGT for short-step level walking and ascending ramps. For ascending ramps, a significantly increased dorsiflexion of 5° during stance and an earlier transition from decelerating to accelerating forces were found with NGT.
When standing on slopes, the symmetry of weight distribution between the orthotic and unaffected limb was significantly increased with NGT.

Conclusions
The increased and resistance-controlled dorsiflexion of the new orthotic ankle joint principle resulted in relevant benefits in gait situations with unlevel conditions and higher demands. Therefore, this orthotic ankle joint principle may represent an additional option to optimize patient fittings with SCOs.

Clinical Relevance Statement
The use of the new orthotic ankle principle tested in the present study results in relevant benefits, especially in gait situations in unlevel conditions. Therefore, this principle represents an additional option to optimize patient fittings with SCOs.
Expansion of Reconstructive Surgical Capacity in Vietnam: Experience from the ReSurge Global Training Program
Authors: Luan Anna , Hau Le Thua Trung , Thom Dang Hoang , Viet Phu Quoc , Auten Brieanne , Chang James 
Published: January 2022

Background:
Building local surgical capacity in low-income and middle-income countries is critical to addressing the unmet global surgical need. Visiting educator programs can be utilized to train local surgeons, but the quantitative impact on surgical capacity has not yet been fully described. The authors’ objective was to evaluate the effectiveness of training utilizing a visiting educator program on local reconstructive surgical capacity in Vietnam.

Methods:
A reconstructive surgery visiting educator program was implemented in Vietnam. Topics of training were based on needs defined by local surgeons, including those specializing in hand surgery, microsurgery, and craniofacial surgery. A retrospective analysis of annual case numbers corresponding to covered topics between the years 2014 and 2019 at each hospital was conducted to determine reconstructive surgical volume and procedures per surgeon over time. Direct costs, indirect costs, and value of volunteer services for each trip were calculated.

Results:
Over the course of 5 years, 12 visiting educator trips were conducted across three hospitals in Vietnam. Local surgeons subsequently independently performed a total of 2018 operations corresponding to topics covered during visiting educator trips, or a mean of 136 operations annually per surgeon. Within several years, the hospitals experienced an 81.5 percent increase in surgical volume for these reconstructive clinical conditions, and annual case volume continues to increase over time. Total costs were $191,290, for a mean cost per trip of $15,941.

Conclusions:
Surgical capacity can be successfully expanded by utilizing targeted visiting educator trips to train local reconstructive surgeons. Local providers ultimately independently perform an increased volume of complex procedures and provide further training to others.
Perceptions of Doctors’ Empathy and Patients’ Subjective Health Status at an Online Clinic: Development of an Empathic Anamnesis Questionnaire
Authors: Martikainen Silja , Falcon Mari , Wikström Valtteri , Peltola Soili , Saarikivi Katri 
Published: January 2022

ABSTRACT

Objective
Medical doctors’ empathy is known to support patients’ health status after face-to-face clinical visits. However, the role of doctors’ empathy in chat-based encounters is not yet well understood. This study investigates whether patients’ evaluations of doctors’ empathy are associated with their health perceptions after a meeting at an online clinic and whether experiences of empathy could be enhanced by augmenting an automated anamnesis questionnaire completed before the visit.

Methods
A total of 209 adult patients agreed to participate in the study. First 103 patients filled out the regular version of the questionnaire (June–August 2019) and then 106 filled out the augmented version of the online anamnesis questionnaire (August–November 2019). Patients’ perceptions of doctors’ empathy were measured with the Consultation and Relational Empathy questionnaire. Patients’ self-perceived health status, potential confounders, and demographic background information were measured via questionnaires.

Results
Patients’ perceptions of doctors’ empathy during a chat-based encounter were associated with patients being less concerned about their symptoms (estimated odds ratios varied between 0.45 and 0.55 depending on the model, p values < .003) and considering their symptoms as less severe (estimated odds ratios = 0.54–0.61, p values < .007), as well as a higher probability of alleviation of symptoms as rated by the patients (estimated odds ratios = 2.16–2.24, p values < .001). Augmenting the anamnesis questionnaire did not affect patient reports on doctors’ overall empathy, but it did have positive effects on specific areas of doctors’ empathy covered by the questionnaire.

Conclusions
These results show that patients’ experience of doctors’ empathy not only is important during face-to-face encounters but also supports patients’ perceptions of health when the interaction is text based. The results also encourage further development of means to support patients’ experiences of empathy during online interaction with medical doctors.