bluuebunny/crossref_metadata_2025 huggingface dataset:
MADS-box protein PpDAM6 regulates chilling requirement-mediated dormancy and bud break in peach
Authors: Zhao Ya-Lin , Li Yong , Cao Ke , Yao Jia-Long , Bie Hang-Ling , Khan Irshad Ahmad , Fang Wei-Chao , Chen Chang-Wen , Wang Xin-Wei , Wu Jin-Long , Guo Wen-Wu , Wang Li-Rong
Published: May 2023

Bud dormancy is crucial for winter survival and is characterized by the inability of the bud meristem to respond to growth-promotive signals before the chilling requirement (CR) is met. However, our understanding of the genetic mechanism regulating CR and bud dormancy remains limited. This study identified PpDAM6 (DORMANCY-ASSOCIATED MADS-box) as a key gene for CR using a genome-wide association study analysis based on structural variations in 345 peach (Prunus persica (L.) Batsch) accessions. The function of PpDAM6 in CR regulation was demonstrated by transiently silencing the gene in peach buds and stably overexpressing the gene in transgenic apple (Malus × domestica) plants. The results showed an evolutionarily conserved function of PpDAM6 in regulating bud dormancy release, followed by vegetative growth and flowering, in peach and apple. The 30-bp deletion in the PpDAM6 promoter was substantially associated with reducing PpDAM6 expression in low-CR accessions. A PCR marker based on the 30-bp indel was developed to distinguish peach plants with non-low and low CR. Modification of the H3K27me3 marker at the PpDAM6 locus showed no apparent change across the dormancy process in low- and non-low- CR cultivars. Additionally, H3K27me3 modification occurred earlier in low-CR cultivars on a genome-wide scale. PpDAM6 could mediate cell–cell communication by inducing the expression of the downstream genes PpNCED1 (9-cis-epoxycarotenoid dioxygenase 1), encoding a key enzyme for ABA biosynthesis, and CALS (CALLOSE SYNTHASE), encoding callose synthase. We shed light on a gene regulatory network formed by PpDAM6-containing complexes that mediate CR underlying dormancy and bud break in peach. A better understanding of the genetic basis for natural variations of CR can help breeders develop cultivars with different CR for growing in different geographical regions.
Metabolome plasticity in 241Arabidopsis thalianaaccessions reveals evolutionary cold adaptation processes
Authors: Weiszmann Jakob , Walther Dirk , Clauw Pieter , Back Georg , Gunis Joanna , Reichardt Ilka , Koemeda Stefanie , Jez Jakub , Nordborg Magnus , Schwarzerova Jana , Pierides Iro , Nägele Thomas , Weckwerth Wolfram
Published: May 2023

Acclimation and adaptation of metabolism to a changing environment are key processes for plant survival and reproductive success. In the present study, 241 natural accessions of Arabidopsis (Arabidopsis thaliana) were grown under two different temperature regimes, 16 °C and 6 °C, and growth parameters were recorded, together with metabolite profiles, to investigate the natural genome × environment effects on metabolome variation. The plasticity of metabolism, which was captured by metabolic distance measures, varied considerably between accessions. Both relative growth rates and metabolic distances were predictable by the underlying natural genetic variation of accessions. Applying machine learning methods, climatic variables of the original growth habitats were tested for their predictive power of natural metabolic variation among accessions. We found specifically habitat temperature during the first quarter of the year to be the best predictor of the plasticity of primary metabolism, indicating habitat temperature as the causal driver of evolutionary cold adaptation processes. Analyses of epigenome- and genome-wide associations revealed accession-specific differential DNA-methylation levels as potentially linked to the metabolome and identified FUMARASE2 as strongly associated with cold adaptation in Arabidopsis accessions. These findings were supported by calculations of the biochemical Jacobian matrix based on variance and covariance of metabolomics data, which revealed that growth under low temperatures most substantially affects the accession-specific plasticity of fumarate and sugar metabolism. Our findings indicate that the plasticity of metabolic regulation is predictable from the genome and epigenome and driven evolutionarily by Arabidopsis growth habitats.
The Solar Ultraviolet Imaging Telescope: detector characterization and readout electronics testing
Authors: Varma S V Manoj , Tyagi Anurag , Joshi Bhushan , Yadav Reena , Chordia Pravin , Kumar Ghanshyam , Sinha Sakya , Burse Mahesh , Padinhatteri Sreejith , Deogaonkar Rushikesh , Ramaprakash A N , Ghosh Avyarthana , Tripathi Durgesh , Sarkar Janmejoy , Sankarasubramanian K , Nagaraju K , Vadodariya Koushal , Kesharwani Ravi , Khan Aafaque , Olekar Manjunath , Azaruddin Mohamed
Published: May 2023

The Solar Ultraviolet Imaging Telescope (SUIT) is one of the payloads onboard the Aditya-L1 mission. It will perform full disc imaging of the Sun in the near-ultraviolet (UV) wavelength range of 200–400 nm. This provides near-simultaneous observations of the Sun from the photosphere and chromosphere. A back-illuminated, enhanced UV charge coupled device (CCD) of size 4096 (H) × 4136 (V) pixels, with a pixel size of 12 μm, is used as an imaging element in SUIT. The CCD characterization and the readout electronics development and testing were performed in-house at the Space Astronomy Group, U R Rao Satellite Centre, ISRO. The test set-up and procedures are explained and the measured values of various parameters including noise, dark current, gain, linearity, and cross-talk are presented in this paper. The results show a satisfactory performance from the CCD as well as the readout electronics to meet the specifications required by the SUIT payload.
Modulation of WNT, Activin/Nodal, and MAPK Signaling Pathways Increases Arterial Hemogenic Endothelium and Hematopoietic Stem/Progenitor Cell Formation During Human iPSC Differentiation
Authors: Li Yongqin , Ding Jianyi , Araki Daisuke , Zou Jizhong , Larochelle Andre
Published: May 2023

Several differentiation protocols enable the emergence of hematopoietic stem and progenitor cells (HSPCs) from human-induced pluripotent stem cells (iPSCs), yet optimized schemes to promote the development of HSPCs with self-renewal, multilineage differentiation, and engraftment potential are lacking. To improve human iPSC differentiation methods, we modulated WNT, Activin/Nodal, and MAPK signaling pathways by stage-specific addition of small-molecule regulators CHIR99021, SB431542, and LY294002, respectively, and measured the impact on hematoendothelial formation in culture. Manipulation of these pathways provided a synergy sufficient to enhance formation of arterial hemogenic endothelium (HE) relative to control culture conditions. Importantly, this approach significantly increased production of human HSPCs with self-renewal and multilineage differentiation properties, as well as phenotypic and molecular evidence of progressive maturation in culture. Together, these findings provide a stepwise improvement in human iPSC differentiation protocols and offer a framework for manipulating intrinsic cellular cues to enable de novo generation of human HSPCs with functionality in vivo.
Milk osteopontin promotes intestinal development by up‐regulating the expression of integrin αvβ3 and CD44
Authors: Jiang Rulan , Lo Jamie , Prell Christine , Lönnerdal Bo
Published: May 2023

Osteopontin (OPN) is a pleiotropic protein involved in numerous biological processes such as cell proliferation and differentiation. Since OPN is abundantly present in milk and is known to be relatively resistant to in vitro gastrointestinal digestion, the current study aimed to investigate the roles of oral intake of milk OPN in intestinal development using an established OPN knockout (KO, OPN−/−) mouse model, in which wild‐type (WT, OPN+/+) mouse pups were nursed by either WT (OPN+/+OPN+ group) or OPN KO dams (OPN+/+OPN− group; +/+ indicates genotype and − indicates milk without OPN), receiving milk with or without OPN from postnatal days 0 to 21 (P0−P21). Our results showed that milk OPN is resistant to in vivo digestion. Compared to OPN+/+OPN− pups, OPN+/+OPN+ pups at P4 and P6 had significantly longer small intestines, at P10 and P20 had larger inner jejunum surfaces, and at P30 exhibited more mature/differentiated intestines, as revealed by higher activities of alkaline phosphatase in brush border and more goblet cells, enteroendocrine cells, and Paneth cells. qRT‐PCR and immunoblotting results showed that milk OPN increased the expression of integrin αv, integrin β3, and CD44 in jejunum of mouse pups (P10, P20, and P30). Immunohistochemistry analysis showed that both integrin αvβ3 and CD44 are localized in jejunum crypts. In addition, milk OPN increased the phosphorylation/activation of the ERK, PI3K/Akt, Wnt, and FAK signaling pathways. In summary, oral intake of milk OPN in early life promotes intestinal proliferation and differentiation by upregulating the expression of integrin αvβ3 and CD44 and thus regulates OPN‐integrin αvβ3 and OPN‐CD44 mediated cellular signaling pathways.
Abaloparatide prevents immobilization‐induced cortical but not trabecular bone loss after spinal cord injury
Authors: Sahbani Karim , Pan Jiangping , Zaidi Mone , Cardozo Christopher P. , Bauman William A. , Tawfeek Hesham A.
Published: May 2023

Spinal cord injury (SCI) causes severe and resistant sublesional disuse bone loss. Abaloparatide, a modified parathyroid hormone related peptide, is an FDA approved drug for treatment of severe osteoporosis with potent anabolic activity. The effects of abaloparatide on SCI‐induced bone loss remain undefined. Thus, female mice underwent sham or severe contusion thoracic SCI causing hindlimb paralysis. Mice then received subcutaneous injection of vehicle or 20 μg/kg/day abaloparatide for 35 days. Micro‐computed tomography (micro‐CT) analysis of the distal and midshaft femoral regions of the SCI‐vehicle mice revealed reduced trabecular fractional bone volume (56%), thickness (75%), and cortical thickness (80%) compared to sham‐vehicle controls. Treatment with abaloparatide did not prevent SCI‐induced changes in trabecular or cortical bone. However, histomorphometry evaluation of the SCI‐abaloparatide mice demonstrated that abaloparatide treatment increased osteoblast (241%) and osteoclast (247%) numbers and the mineral apposition rate (131%) compared to SCI‐vehicle animals. In another independent experiment, treatment with 80 μg/kg/day abaloparatide significantly attenuated SCI‐induced loss in cortical bone thickness (93%) when compared to SCI‐vehicle mice (79%) but did not prevent SCI‐induced trabecular bone loss or elevation in cortical porosity. Biochemical analysis of the bone marrow supernatants of the femurs showed that SCI‐abaloparatide animals had 2.3‐fold increase in procollagen type I N‐terminal propeptide, a bone formation marker than SCI‐vehicle animals. SCI groups had 70% higher levels of cross‐linked C‐telopeptide of type I collagen, a bone resorption marker, than sham‐vehicle mice. These findings suggest that abaloparatide protects the cortical bone against the deleterious effects of SCI by promoting bone formation.
Tumor‐derived semaphorin 3D promoting cancer cachexia via regulating hypothalamic pro‐opiomelanocortin neurons
Authors: Zhang Yanni , Xi Qiulei , Zhong Ming , Jiang Yi , Zhuang Qiulin , Ding Zuoyou , Tan Shanjun , Wang Junjie , Liu Hao , Zhang Zhige , Zhou Ben , Wu Guohao
Published: May 2023

Cachexia is very common in cancer patients and predicts a poor prognosis; however, the molecular basis for progress in these individuals remains unclear, especially the effect of tumors on the hypothalamus energy regulation center. To investigate the regulatory pathway of tumors associated with hypothalamic pro‐opiomelanocortin (POMC) neurons known as appetite‐inhibiting neurons, we conducted observations both on patients and mice models. Results showed that the highly expressed exocrine semaphorin 3D (SEMA3D) both in cachexia patients and mice was positively related to the expression of POMC and its proteolytic peptide. Compared with the control group, mice inoculated with the SEMA3D‐knockout C26 cell line decreased the activity of POMC neurons resulting in a 1.3‐fold increase in food intake, a 22.2% increase in body weight, and reduced skeletal muscle and fat catabolism. The effect of SEMA3D on cachexia progression can be partially alleviated by knocking‐down POMC expression in the brain. In terms of mechanism, SEMA3D enhances the activity of POMC neurons by activating the expression of NRP2 (membrane receptor) and PlxnD1 (intracellular receptor). Our research revealed the overexpression of SEMA3D in tumors works as an activator of POMC neurons, which may play a vital role in suppressing appetite and promoting catabolic metabolism.
Effect of a Workshop to Break the Bias Habit for Internal Medicine Faculty: A Multisite Cluster Randomized Controlled Study
Authors: Carnes Molly , Sheridan Jennifer , Fine Eve , Lee You-Geon , Filut Amarette
Published: May 2023

Purpose

Recognition that cultural stereotypes can unintentionally perpetuate inequities throughout academic medicine has led to calls for “implicit bias training” without strong evidence to support these recommendations and some evidence of potential harm. The authors sought to determine the effectiveness of a single 3-hour workshop in helping department of medicine faculty overcome implicit stereotype-based bias and in improving the climate in the working environment.

Method

A multisite cluster randomized controlled study (October 2017 to April 2021) with clustering at the level of divisions within departments and participant-level analysis of survey responses involved 8,657 faculty in 204 divisions in 19 departments of medicine: 4,424 in the intervention group (1,526 attended a workshop) and 4,233 in the control group. Online surveys at baseline (3,764/8,657 = 43.48% response rate) and 3 months after the workshop (2,962/7,715 = 38.39% response rate) assessed bias awareness, bias-reducing intentional behavioral change, and perceptions of division climate.

Results

At 3 months, faculty in the intervention vs control divisions showed greater increases in awareness of personal bias vulnerability (b = 0.190 [95% CI, 0.031 to 0.349], P = .02), bias reduction self-efficacy (b = 0.097 [95% CI, 0.010 to 0.184], P = .03), and taking action to reduce bias (b = 0.113 [95% CI, 0.007 to 0.219], P = .04). The workshop had no effect on climate or burnout, but slightly increased perceptions of respectful division meetings (b = 0.072 [95% CI, 0.0003 to 0.143], P = .049).

Conclusions

Results of this study should give confidence to those designing prodiversity interventions for faculty in academic medical centers that a single workshop which promotes awareness of stereotype-based implicit bias, explains and labels common bias concepts, and provides evidence-based strategies for participants to practice appears to have no harms and may have significant benefits in empowering faculty to break the bias habit.
Form and Function: Technique for Free Functional Gracilis Harvest With Greater Saphenous Vein for Large Skin Paddle
Authors: Graf Alexander , Ojemakinde Akinade , Gupta Sachin , Zelenski Nicole A. , Levin L. Scott
Published: May 2023

Free functional gracilis transfer is a technique for restoration of upper extremity function following brachial plexus injury, as well as muscle loss from traumatic, oncologic, and congenital causes. However, when used for the latter applications, a functional muscle as well as large skin paddle can be required. Historically, skin paddle size was limited by venous outflow of the gracilis flap, using 1 or 2 venae comitantes, and large unreliable skin paddles resulting in partial necrosis. Therefore, to restore form and function, we herein present a technique of free functional gracilis muscle harvest with inclusion of adjacent greater saphenous vein for inclusion of a large skin paddle with 2 venous drainage systems.
Length of stay and inpatient charges of total knee arthroplasty in China: analysis of a national database
Authors: Long Huizhong , Zeng Chao , Shi Ying , Wang Haibo , Xie Dongxing , Lei Guanghua
Published: May 2023

Background:

There are limited data on the resource utilization of total knee arthroplasty (TKA) in China. This study aimed to examine the length of stay (LOS) and inpatient charges of TKA in China, and to investigate their determinants.

Methods:

We included patients undergoing primary TKA in the Hospital Quality Monitoring System in China between 2013 and 2019. LOS and inpatient charges were obtained, and their associated factors were further assessed using multivariable linear regression.

Results:

A total of 184,363 TKAs were included. The LOS decreased from 10.8 days in 2013 to 9.3 days in 2019. The admission-to-surgery interval decreased from 4.6 to 4.2 days. The mean inpatient charges were 61,208.3 Chinese Yuan. Inpatient charges reached a peak in 2016, after which a gradual decrease was observed. Implant and material charges accounted for a dominating percentage, but they exhibited a downward trend, whereas labor-related charges gradually increased. Single marital status, non-osteoarthritis indication, and comorbidity were associated with longer LOS and higher inpatient charges. Female sex and younger age were associated with higher inpatient charges. There were apparent varieties of LOS and inpatient charges among provincial or non-provincial hospitals, hospitals with various TKA volume, or in different geographic regions.

Conclusions:

The LOS following TKA in China appeared to be long, but it was shortened during the time period of 2013 to 2019. The inpatient charges dominated by implant and material charges exhibited a downward trend. However, there were apparent sociodemographic and hospital-related discrepancies of resource utilization. The observed statistics can lead to more efficient resource utilization of TKA in China.
Rapid Conversion to a Completely Virtual Multidisciplinary ALS Clinic in Response to the COVID-19 Pandemic: Implications for Future Care Delivery
Authors: Grogan James , Walsh Susan , Haulman Anne , Yazgi Habib , Geronimo Andrew , Mamarabadi Mansoureh , Simmons Zachary
Published: May 2023

Objectives:

The goals of this study were to assess the feasibility of maintaining multidisciplinary remote care, patient preferences, and outcomes of this transition because of COVID-19.

Methods:

From March 18, 2020 to June 3, 2020, 127 patients with amyotrophic lateral sclerosis (ALS) who were scheduled to be seen in our ALS clinic were contacted and scheduled according their preference for a telemedicine visit, telephone visit, or postponement until the next available in-person visit. Age, time from disease onset, ALS Functional Rating Scale-Revised, patient choices, and outcomes were recorded.

Results:

Patient visit preferences were 69% telemedicine, 21% telephone, and 10% postpone for a later in-clinic visit. Patients with higher ALS Functional Rating Scale-Revised were more likely to choose the next in-person opening (P = 0.04). Age and time from disease onset were not related to visit type preference. There were 118 virtual encounters, of which 91 (77%) began as telemedicine and 27 (23%) as telephone visits. Most telemedicine visits were conducted successfully, but 10 were converted to a telephone visit. The clinic maintained 88.6% of patient volume compared with the prior year, during which most visits were in-person.

Conclusions:

Telemedicine care using synchronous videoconferencing is preferable and feasible for most patients on short notice, with telephone as back-up. Clinic volumes can be maintained. These findings support the conversion of a multidisciplinary ALS clinic to 1 with exclusively virtual visits when future events again disrupt in-person care.
Impact of vitamin D supplementation on modulating heat-shock proteins in postmenopausal women: a randomized, double-blind, placebo-controlled study
Authors: Orsatti Claudio Lera , Orsatti Fábio Lera , de Souza João Pedro Esteves Alves , Nahas Eliana Aguiar Petri
Published: May 2023

Objective

The aim of this study was to examine the effect of vitamin D (VitD) supplementation on serum heat-shock proteins (HSP) in postmenopausal women (PW).

Methods

In this double-blind, placebo-controlled trial, 160 PW aged 45 to 65 years with amenorrhea 12 months or more were randomized into two groups: 80 PW in VitD group (oral supplementation with 1,000 IU VitD3/d) or 80 PW in placebo group. The PW were assessed at baseline and after 10 months of intervention. Plasma concentrations of 25-hydroxyVitD (25[OH]D) were measured by high-performance liquid chromatography. HSP27/pS78/pS82, HSP27/total, HSP60, HSP70/72, and HSP90α levels were assessed in serum using a multiplexed bead immunoassay.

Results

HSP27 (pS78/pS82 [P < 0.035] and total [P < 0.001]) levels increased in the supplemented group when compared with the control group. There was no effect of VitD supplementation on HSP60, HSP70/72, and HSP90α levels.

Conclusions

Vitamin D supplementation increases serum HSP27 level in PW.
Circulating cell-free messenger RNA secretome characterization of primary sclerosing cholangitis
Authors: Chalasani Naga , Vuppalanchi Raj , Lammert Craig , Gawrieh Samer , Braun Jerome V. , Zhuang Jiali , Ibarra Arkaitz , Ross David A. , Nerenberg Michael , Quake Stephen R. , Sninsky John J. , Toden Shusuke
Published: May 2023

Background:

Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic liver disease characterized by multifocal bile duct strictures. To date, underlying molecular mechanisms of PSC remain unclear, and therapeutic options are limited.

Methods:

We performed cell-free messenger RNA (cf-mRNA) sequencing to characterize the circulating transcriptome of PSC and noninvasively investigate potentially bioactive signals that are associated with PSC. Serum cf-mRNA profiles were compared among 50 individuals with PSC, 20 healthy controls, and 235 individuals with NAFLD. Tissue and cell type-of-origin genes that are dysregulated in subjects with PSC were evaluated. Subsequently, diagnostic classifiers were developed using PSC dysregulated cf-mRNA genes.

Results:

Differential expression analysis of the cf-mRNA transcriptomes of PSC and healthy controls resulted in identification of 1407 dysregulated genes. Furthermore, differentially expressed genes between PSC and healthy controls or NAFLD shared common genes known to be involved in liver pathophysiology. In particular, genes from liver- and specific cell type-origin, including hepatocyte, HSCs, and KCs, were highly abundant in cf-mRNA of subjects with PSC. Gene cluster analysis revealed that liver-specific genes dysregulated in PSC form a distinct cluster, which corresponded to a subset of the PSC subject population. Finally, we developed a cf-mRNA diagnostic classifier using liver-specific genes that discriminated PSC from healthy control subjects using gene transcripts of liver origin.

Conclusions:

Blood-based whole-transcriptome cf-mRNA profiling revealed high abundance of liver-specific genes in sera of subjects with PSC, which may be used to diagnose patients with PSC. We identified several unique cf-mRNA profiles of subjects with PSC. These findings may also have utility for noninvasive molecular stratification of subjects with PSC for pharmacotherapy safety and response studies.
Impact of body composition in advanced hepatocellular carcinoma: A subanalysis of the SORAMIC trial
Authors: Surov Alexey , Thormann Maximilian , Hinnerichs Mattes , Seidensticker Max , Seidensticker Ricarda , Öcal Osman , Schütte Kerstin , Zech Christoph J. , Loewe Christian , van Delden Otto , Vandecaveye Vincent , Verslype Chris , Gebauer Bernhard , Sengel Christian , Bargellini Irene , Iezzi Roberto , Berg Thomas , Klümpen Heinz J. , Benckert Julia , Gasbarrini Antonio , Amthauer Holger , Sangro Bruno , Malfertheiner Peter , Omari Jazan , Wienke Andreas , Ricke Jens , Pech Maciej
Published: May 2023

Background:

Body composition parameters have been reported to be prognostic factors in patients with oncologic diseases. However, the available data on patients with HCC are conflicting. The aim of this study was to assess the impact of body composition on survival in patients with HCC treated with sorafenib or selective internal radioembolization (SIRT) and sorafenib.

Methods:

This is an exploratory subanalysis of the prospective, randomized controlled SORAMIC trial. Within the palliative arm of the study, patients were selected if a baseline abdominal CT was available. A broad set of skeletal muscle and adipose tissue parameters were measured at the L3 level. Low skeletal muscle mass (LSMM) and density parameters were defined using published cutoffs. The parameters were correlated with overall survival.

Results:

Of 424 patients in the palliative study arm, 369 patients were included in the analysis. There were 192 patients in the combined sorafenib/SIRT and 177 patients in the sorafenib group. Median overall survival was 9.9 months for the entire cohort and 10.8 and 9.2 months for the SIRT/sorafenib and sorafenib groups, respectively. There was no relevant association of either body composition parameter with overall survival in either the overall cohort or in the SIRT/sorafenib or sorafenib subgroups.

Conclusions:

This subanalysis of the prospective SORAMIC trial does not suggest a relevant influence of body composition parameters of survival in patients with advanced HCC. Body composition parameters therefore do not serve in patient allocation in this palliative treatment cohort.
Home-Based Cardiac Rehabilitation Among Patients Unwilling to Participate in Hospital-Based Programs
Authors: Nabutovsky Irene , Breitner Daniel , Heller Alexis , Levine Yoav , Moreno Merav , Scheinowitz Mickey , Levin Chedva , Klempfner Robert
Published: May 2023

Purpose:

Asynchronous home-based cardiac rehabilitation (HBCR) is a viable alternative to center-based cardiac rehabilitation (CBCR). However, to achieve significant functional improvement, a high level of adherence and activity must be achieved. The effectiveness of HBCR among patients who actively avoid CBCR has not been effectively investigated. This study aimed to investigate the effectiveness of the HBCR program among patients unwilling to participate in CBCR.

Methods:

A randomized prospective study enrolled 45 participants to a 6-mo HBCR program and the remaining 24 were allocated to regular care. Both groups were digitally monitored for physical activity (PA) and self-reported outcomes. Change in peak oxygen uptake (VO2peak), the primary study outcome, was measured by the cardiopulmonary exercise test, immediately before program start and 4 mo thereafter.

Results:

The study included 69 patients, 81% men, aged 55.9 ±12 yr, enrolled in a 6-mo HBCR program to follow a myocardial infarction (25.4%) or coronary interventions (41.3%), heart failure hospitalization (29%), or heart transplantation (10%). Weekly aerobic exercise totaled a median of 193.2 (110.2-251.5) min (129% of set exercise goal), of which 112 (70-150) min was in the heart rate zone recommended by the exercise physiologist.

After 4 mo, VO2peak improved by 10.2% in the intervention group versus −2.7% in the control group (+2.46 ± 2.67 vs −0.72 ± 3.02 mL/kg/min; P < .001).

Conclusion:

The monthly PA of patients in the HBCR versus conventional CBCR group were well within guideline recommendations, showing a significant improvement in cardiorespiratory fitness. Risk level, age, and lack of motivation at the beginning of the program did not prevent achieving goals and maintaining adherence.
Effects of Lifestyle Modification on Psychosocial Function in Patients With Resistant Hypertension
Authors: Blumenthal James A. , Smith Patrick J. , Mabe Stephanie , Hinderliter Alan , Craighead Linda , Watkins Lana L. , Ingle Krista , Tyson Crystal C. , Lin Pao-Hwa , Kraus William E. , Liao Lawrence , Sherwood Andrew
Published: May 2023

Purpose:

In a secondary analysis of the TRIUMPH clinical trial, psychological outcomes in patients with resistant hypertension (RH) receiving a diet and exercise intervention delivered in a cardiac rehabilitation setting were compared with those receiving a similar prescription of diet and exercise provided in a single counseling session by a health educator.

Methods:

One hundred forty patients with RH were randomly assigned to a 4-mo program of dietary counseling, behavioral weight management, and exercise (C-LIFE) or a single counseling session providing standardized education and physician advice (SEPA). Participants completed a battery of questionnaires to assess psychological functioning before and after the intervention. A global measure of psychological functioning was derived from the General Health Questionnaire (GHQ), Perceived Stress Scale (PSS), Medical Outcomes Study 36-item Short Form Health Survey, Spielberger State-Trait Anxiety Inventory, Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory-II, and Patient-Reported Outcomes Measurement Information System (PROMIS) Anger scale.

Results:

Participants in the C-LIFE intervention achieved greater improvements in psychological functioning compared with SEPA (C-LIFE: 58.9 [56.1, 61.8] vs SEPA: 66.5 [62.1, 70.9]; P = .024). Greater improvements were especially evident for the GHQ, PSS, and HADS. Examination of mediation revealed that greater weight loss (B =−0.17, P = .004) and improved oxygen uptake (B =−0.12, P = .044) were associated with improved psychological functioning.

Conclusion:

Compared with standard education and physician advice, a structured program of diet and exercise not only reduced blood pressure but also improved psychological functioning in patients with RH.
Deep Morphea in an Immunosuppressed Patient With Anti-U1RNP Myositis: A Case Report
Authors: Berjawi Ahmad , Irani Laure L. , El Khoury Jinane R.
Published: May 2023

Introduction:

Morphea is an inflammatory skin disease characterized by skin thickening due to increased collagen deposition in the dermis or subcutaneous tissues. Anti-U1RNP myositis is a newly described entity characterized by myositis, arthritis, interstitial lung disease, and Raynaud phenomenon.

 We present a case of a unique combination of deep morphea in a patient with anti-U1RNP myositis.

Case presentation:

A 64-year-old male with 5-year history of proximal muscle weakness, polyarthritis, Raynaud phenomenon, and dyspnea on multiple immunosuppressives presented with localized infiltrated, tight, and hyperpigmented plaques over the posterior thighs and mid-to-lower back developing over the last 2 years and limiting his movement. Autoimmune workup revealed a positive ANA, anti-U1RNP antibody, anti-Jo1 antibody, and anti-Ro52 antibody. Further workup showed restrictive lung disease, kidney disease, and arthritis. Patient was diagnosed with anti-U1RNP myositis. Skin biopsy of the back lesion showed deep morphea.

Discussion:

Association of deep morphea with anti-U1RNP myositis is not described prior in the literature. Treatment of morphea is challenging since the patient is already on immunosuppressive medications. The patient failed methotrexate prior and is currently on Mycophenolate mofetil and Deflazacort which are reported as potential treatment for morphea. Therefore, physical therapy plus topical Tacrolimus were suggested as an initial measure to preserve the range of motion of his posterior thighs and back. This is a case of progressive deep morphea developing in a patient with a unique autoimmune profile on immunosuppressive drugs.

Conclusion:

Anti-U1RNP myositis is a challenging diagnosis and should be always thought of in patients with positive anti-U1RNP, myositis, interstitial lung disease, arthritis, kidney disease, and Raynaud phenomenon. Moreover, deep morphea treatment in immunosuppressed patients is challenging and different measures should be considered.
The use of multiple daily injections versus insulin pump therapy for HgbA1c reduction in patients with insulin-dependent type 2 diabetes
Authors: Stallings Dana E. , Higgins Karen J.
Published: May 2023

Background:

More than 35 million Americans live with type 2 diabetes (T2D), resulting in the need for newer strategies and technologies to manage the disease. Insulin pump therapy (IPT) has historically been reserved for type 1 diabetes, although emerging data demonstrates improved glucose outcomes for patients with T2D using IPT.

Purpose:

To measure the change in HgbA1c in patients with T2D after changing therapy from multiple daily injections (MDI) to continuous subcutaneous insulin infusion through IPT.

Methodology:

A retrospective comparison study was conducted by reviewing the electronic medical record of patients with T2D, older than 18 years, who had been on multiple daily insulin injections for at least 1 year, followed by IPT for at least 1 year.

Results:

One hundred seventy-one patients met the inclusion criteria. There was a statistically significant reduction in mean HgbA1c from 9.6% to 7.6%.

Conclusion:

Insulin pump therapy may result in lower HgbA1c levels for T2D not at goal on MDI.

Implications:

Patients on multiple daily insulin injections who are not at goal should be considered for IPT.
Open Surgical Insertion of TandemHeart Device for Left Ventricular Unloading
Authors: Al Rameni Dina , Patel Manish K. , Salas De Armas Ismael A. , Akay Mehmet H. , Marwan Jumean F. , Kar Biswajit , Gregoric Igor D.
Published: May 2023

TandemHeart (Cardiac Assist Inc., Pittsburgh, PA) is a valuable mechanical circulatory support (MCS) device that provides left atrial to femoral artery bypass and directly unloads the left ventricle. The device is inserted under fluoroscopic guidance in the cardiac catheterization laboratory without requiring invasive surgical exposure. However, this device is unique because it directly unloads the oxygenated blood from the left atrium and may be needed for postoperative support in patients undergoing various open cardiac surgeries. In this article, we provide a detailed description of the open surgical insertion of a TandemHeart device.
HLA-DQ antibodies in alloimmunity, what makes them different?
Authors: Meneghini Maria , Tambur Anat R.
Published: May 2023

Purpose of review

De novo HLA-DQ antibodies are the most frequently observed after solid-organ allotransplantation; and are associated with the worse adverse graft outcomes compared with all other HLA antibodies. However, the biological explanation for this observation is not yet known. Herein, we examine unique characteristics of alloimmunity directed specifically against HLA-DQ molecules.

Recent findings

While investigators attempted to decipher functional properties of HLA class II antigens that may explain their immunogenicity and pathogenicity, most early studies focused on the more expressed molecule – HLA-DR. We here summarize up-to-date literature documenting specific features of HLA-DQ, as compared to other class II HLA antigens. Structural and cell-surface expression differences have been noted on various cell types. Some evidence suggests variations in antigen-presenting function and intracellular activation pathways after antigen/antibody interaction.

The clinical effects of donor-recipient incompatibility at HLA-DQ, the risk of generating de novo antibodies leading to rejection, and the inferior graft outcomes indicate increased immunogenicity and pathogenicity that is unique to this HLA antigen. Clearly, knowledge generated for HLA-DR cannot be applied interchangeably. Deeper understanding of features unique to HLA-DQ may support the generation of targeted preventive-therapeutic strategies and ultimately improve solid-organ transplant outcomes.
Advanced Practice Provider Onboarding
Authors: Koppolu Rajashree , Nandwani Monica , Navoa Jesus , Kuriakose Clair
Published: May 2023

With the robust growth in demand for advanced practice providers (APPs), employers must focus on strategies to promote recruitment, retention, and job satisfaction. The authors describe the creation, development, and sustainability of an APP onboarding program to support the initial transition for providers into their new roles within an academic healthcare organization. Advanced practice provider leaders coordinate with multidisciplinary stakeholders to ensure new-hire APPs are equipped with the necessary tools for a successful start.
Visiting Policies and Parental Presence During PICU Admission: A Survey in French Units
Authors: Bergerat Manon , De Saint Blanquat Laure , Milesi Christophe , Grimaud Marion , Le Bourgeois Fleur , Renolleau Sylvain , Pouletty Marie , Oualha Mehdi , Leteurtre Stéphane , Recher Morgan , Béranger Agathe
Published: May 2023

OBJECTIVES:

To describe the policies about parent visiting and involvement in care during admission to French PICUs.

DESIGN:

A structured questionnaire was emailed to the chief of each of 35 French PICUs. Data about visiting policies, involvement in care, evolution of policies, and general characteristics were collected from April 2021 to May 2021. A descriptive analysis was conducted.

SETTING:

Thirty-five PICUs in France.

PATIENTS:

None.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Twenty-nine of 35 (83%) PICUs replied. Twenty-four-hour access for parents was reported for all PICUs responding. Other allowed visitors were grandparents (21/29, 72%) and siblings (19/29, 66%) with professional support. Simultaneous visits were restricted to two visitors in 83% (24/29) of PICUs. Family presence was always permitted during medical rounds for 20 of 29 (69%) PICUs. Most of the units rarely or never allowed parental presence during the most invasive procedures, such as central venous catheter placement (18/29, 62%) and intubation (22/29, 76%).

CONCLUSIONS:

Unrestricted access to the PICU, for both parents, was available in all responding French units. There were, however, restrictions on the number of visitors and the presence of other family members at the bedside. Moreover, permission for parental presence during care procedures was heterogenous, and mainly restricted. National guidelines and educational programs are needed to support family wishes and promote acceptance by healthcare providers in French PICUs.
Point-of-Care Ultrasound, an Unexpected Cardiac Mass in a Neonate
Authors: Barbera Nicole L. , Ekpenyong Atim , Nguyen Mylinh T. , Pade Kathryn H.
Published: May 2023

Neonatal cardiac masses are uncommon and often not obvious based on physical examination or plain radiography. The objective of this clinical case report is to demonstrate how cardiac point-of-care ultrasound was pivotal in the clinical course of a seemingly well neonate with vague symptoms. A 6-week-old male infant presented to the emergency department with fatigue and pallor that was reported to have resolved before arrival. In the emergency department, he had a normal physical examination and stable vital signs. Cardiac point-of-care ultrasound was performed and demonstrated a mass near the mitral valve. These ultrasound findings prompted additional evaluation, cardiology consultation, admission, and subsequent diagnosis of a rhabdomyoma due to tuberous sclerosis.
Scarless Donor Site for Breast Reconstruction by Endoscopically Assisted Extended Latissimus Dorsi Flap plus Lipofilling
Authors: Akita Shinsuke , Tokumoto Hideki , Yamaji Yoshihisa , Kosaka Kentaro , Arai Minami , Ando Nobuhiro , Maei Haruka , Kubota Yoshitaka , Fujimoto Hiroshi , Mitsukawa Nobuyuki
Published: May 2023

Background:

Breast reconstruction using endoscopically assisted latissimus dorsi (LD) flap leaves no scar on the back; however, the small amount of tissue obtained makes this procedure less practical. This study aimed to propose a new technique of endoscopically assisted extended LD (eeLD) flap plus lipofilling, which could secure a large breast volume.

Methods:

Lateral thoracic adipose tissues supplied by the thoracodorsal artery branches and the LD muscle were elevated as a single unit only through the mastectomy scar and three ports through the lateral chest. Furthermore, fat was simultaneously injected to support the volume and shape of the breast. Changes in the volume of the reconstructed breast over time were measured using three-dimensional stereophotogrammetry.

Results:

Overall, 15 breasts of 14 patients who underwent breast reconstruction using an eeLD flap exhibited no serious complications. On average, 281.9 ± 32.4 g of flap and 74.7 ± 19.4 mL of lipofilling were used. Within 8 weeks after the procedure, the volume of the reconstructed breast decreased to 69.5 ± 7.5% and then plateaued. Seven patients needed a subsequent session of lipofilling to acquire adequate breast volume and projection. Notably, according to the BREAST-Q back scores, patients who underwent eeLD flap surgery were significantly more satisfied than those who underwent conventional LD musculocutaneous flap surgery using a skin paddle on the back at the same institution (82.8 ± 9.2 versus 62.6 ± 6.3; P < 0.0001).

Conclusion:

Despite the limitations in volume, eeLD flap plus lipofilling is advantageous because it does not leave a noticeable donor-site scar.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
The Effect of Calf Subcutaneous Fat Thickness on Patient Satisfaction after Calf Contouring with Botulinum Toxin A
Authors: Xu Xiangwen , Liu Dandan , Wu Mengfan , Luo Lin , Feng Jun , Ou Yanting , Kang Yixing , Panayi Adriana C. , Long Yun , Cui Yongyan
Published: May 2023

Background:

As a minimally invasive therapy, botulinum toxin A (BTXA) treatment effectively reduces the hypertrophy of the gastrocnemius muscle (GM). Patient satisfaction is, however, reported to be low after treatment, with a possible correlation between high satisfaction and thinner subcutaneous fat. The goal of this study was to classify the subcutaneous fat of calves to understand the relation between fat thickness and patient satisfaction after BTXA treatment.

Methods:

The maximal leg circumference was measured, and B-mode ultrasound was used to measure the thickness of the medial head of the GM and of the subcutaneous fat. Patients were followed up at 1 and 6 months after BTXA treatment.

Results:

A total of 50 cases were classified into the following levels of fat thickness: slim (<0.55 cm), moderate (0.55 to 0.85 cm), and bulge (>0.85 cm). All patients were treated with 300 units of BTXA. Patients in the slim and bulge groups reported higher satisfaction rate than patients in the moderate group, with patients in the slim and bulge groups reporting complete satisfaction (100%) with calf contour at the 6-month follow-up. The satisfaction rate with the improvement in total leg circumference was low in all 3 groups. No severe complications were encountered in this study.

Conclusions:

This study identified a U-shaped correlation between calf subcutaneous fat thickness and patient satisfaction rate after treatment. The authors’ results provide a theoretical basis for BTXA treatment and suggest the importance of preprocedure conversations in GM hypertrophy treatment.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
Refinements in the Preexpanded Distant Flap for Giant Melanocytic Nevi of the Upper Extremity in Pediatric Patients
Authors: Kim Ji-Young , Choi Tae Hyun , Kim Byung Jun
Published: May 2023

Background:

Surgical treatment of large and giant congenital melanocytic nevi (GCMN) of the upper extremity is challenging because of limited options for reconstruction. A preexpanded distant flap is considered an important option in upper extremity reconstruction, where the soft tissue available for use is limited. The authors aimed to refine the preexpanded distant flap after excision of the GCMN in the upper extremity.

Methods:

Large (>10 cm) and giant (>20 cm) congenital melanocytic nevi of the upper extremities treated with tissue expansion and distant flaps over 10 years were retrospectively reviewed, and the authors describe in detail the surgical strategies for reconstruction of the upper extremity with a distant flap.

Results:

From March of 2010 to February of 2020, 13 patients (mean age, 2.87 years) treated with 17 preextended distant flaps were included. The mean flap dimension was 154.87 cm2, ranging from 15 × 5 to 26.5 × 11 cm. All procedures were successfully completed except for one, in which partial flap necrosis occurred. Preconditioning was performed before flap transfer in 5 patients with larger rotation arcs and flap dimensions. The mean duration of postoperative follow-up was 51.85 months. A new reconstructive protocol was proposed that combined the 3 elements, including a distant flap, tissue expander, and preconditioning.

Conclusions:

In the treatment of GCMN in the upper extremities, careful planning and multiple stages are required. For pediatric patients, the preextended distant flap with preconditioning is useful and effective for reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Universal HIV Testing and Treatment With Patient-Centered Care Improves ART Uptake and Viral Suppression Among Adults Reporting Hazardous Alcohol Use in Uganda and Kenya
Authors: Puryear Sarah B. , Ayieko James , Hahn Judith A. , Mucunguzi Atukunda , Owaraganise Asiphas , Schwab Joshua , Balzer Laura B. , Kwarisiima Dalsone , Charlebois Edwin D. , Cohen Craig R. , Bukusi Elizabeth A. , Petersen Maya L. , Havlir Diane V. , Kamya Moses R. , Chamie Gabriel
Published: May 2023

Objectives:

Determine whether patient-centered, streamlined HIV care achieves higher antiretroviral therapy (ART) uptake and viral suppression than the standard treatment model for people with HIV (PWH) reporting hazardous alcohol use.

Design:

Community cluster-randomized trial.

Methods:

The Sustainable East Africa Research in Community Health trial (NCT01864603) compared an intervention of annual population HIV testing, universal ART, and patient-centered care with a control of baseline population testing with ART by country standard in 32 Kenyan and Ugandan communities. Adults (15 years or older) completed a baseline Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) and were classified as no/nonhazardous (AUDIT-C 0–2 women/0–3 men) or hazardous alcohol use (≥3 women/≥4 men). We compared year 3 ART uptake and viral suppression of PWH reporting hazardous use between intervention and control arms. We compared alcohol use as a predictor of year 3 ART uptake and viral suppression among PWH, by arm.

Results:

Of 11,070 PWH with AUDIT-C measured, 1723 (16%) reported any alcohol use and 893 (8%) reported hazardous use. Among PWH reporting hazardous use, the intervention arm had higher ART uptake (96%) and suppression (87%) compared with control (74%, adjusted risk ratio [aRR] = 1.28, 95% CI: 1.19 to 1.38; and 72%, aRR = 1.20, 95% CI: 1.10 to 1.31, respectively). Within arm, hazardous alcohol use predicted lower ART uptake in control (aRR = 0.86, 95% CI: 0.78 to 0.96), but not intervention (aRR = 1.02, 95% CI: 1.00 to 1.04); use was not predictive of suppression in either arm.

Conclusions:

The Sustainable East Africa Research in Community Health intervention improved ART uptake and viral suppression among PWH reporting hazardous alcohol use and eliminated gaps in ART uptake between PWH with hazardous and no/nonhazardous use. Patient-centered HIV care may decrease barriers to HIV care for PWH with hazardous alcohol use.