bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tracking Symptoms of Patients With Lymphedema Before and After Power-Assisted Liposuction Surgery
Authors: Bustos Valeria P. , Friedman Rosie , Pardo Jaime A. , Granoff Melisa , Fu Mei R. , Singhal Dhruv 
Published: March 2023

Purpose
Lymphedema negatively impacts patients from a psychosocial standpoint and consequently affects patient's quality of life. Debulking procedures using power-assisted liposuction (PAL) are currently deemed an effective treatment for fat-dominant lymphedema and improves anthropometric measurements as well as quality of life. However, there have been no studies specifically evaluating changes in symptoms related to lymphedema after PAL. An understanding of how symptoms change after this procedure would be valuable for preoperative counseling and to guide patient expectations.

Methods
A cross-sectional study was performed in patients with extremity lymphedema who underwent PAL from January 2018 to December 2020 at a tertiary care facility. A retrospective chart review and follow-up phone survey were conducted to compare signs and symptoms related to lymphedema before and after PAL.

Results
Forty-five patients were included in this study. Of these, 27 patients (60%) underwent upper extremity PAL and 18 patients (40%) underwent lower extremity PAL. The mean follow-up time was 15.5±7.9 months. After PAL, patients with upper extremity lymphedema reported having resolved heaviness (44%), as well as improved achiness (79%) and swelling (78%). In patients with lower extremity lymphedema, they reported having improved all signs and symptoms, particularly swelling (78%), tightness (72%), and achiness (71%).

Conclusions
In patients with fat-dominant lymphedema, PAL positively impacts patient-reported outcomes in a sustained fashion over time. Continuous surveillance of postoperative studies is required to elucidate factors independently associated with the outcomes found in our study. Moreover, further studies using a mixed method approach will help us better understand patient's expectations to achieve informed decision and adequate treatment goals.
Satisfaction With Information Predicts Satisfaction With Outcome and Surgeon in Black and Hispanic Patients Undergoing Breast Reconstruction
Authors: Zong Amanda M. , Leibl Kayla E. , Weichman Katie E. 
Published: March 2023

BackgroundRacial disparities in American healthcare contribute to worse outcomes among minority patients. Minority patients undergoing breast reconstruction are more likely to report dissatisfaction with their reconstruction process as compared with White patients, yet there is limited research exploring contributory factors. This study investigates which process-of-care, clinical, and surgical variables are most strongly correlated with Black and Hispanic patients' reported satisfaction.MethodsA retrospective review of all patients who underwent postmastectomy breast reconstruction at a single academic center from 2015 to 2021 was performed. Patients were included for analysis if they identified as Black or Hispanic and completed preoperative, less than 1-year postoperative, and 1- to 3-year postoperative BREAST-Q surveys. At both postoperative time points, the association between satisfaction with outcome and surgeon and selected independent variables was determined using regression analysis.ResultsOne hundred eighteen Black and Hispanic patients were included for analysis, with average age 49.59 ± 9.51 years and body mass index 30.11 ± 5.00 kg/m2. In the multivariate model for predicting satisfaction with outcome, only satisfaction with preoperative information (P< 0.001) was a statistically significant predictor during early and late postoperative evaluations. For predicting satisfaction with surgeon, satisfaction with information (P< 0.001) remained a significant predictor in the early and late postoperative evaluations, with lower body mass index as an additionally significant predictor during the late postoperative period.ConclusionsPatient satisfaction with preoperative information received is the single most significant factor associated with Black and Hispanic patient satisfaction with outcome and plastic surgeon. This finding encourages further research on effective and culturally inclusive information delivery so as to both improve patient satisfaction and reduce healthcare disparities.
Plastic Surgery Roles in Wound Centers in the Northeastern United States
Authors: Lin Andrea , Lu Stephen 
Published: March 2023

Introduction
Wound care is a substantial industry costing nearly $19 billion USD, and dedicated wound care centers play a critical role via a multidisciplinary team-based approach. At the same time, plastic surgeons are often considered experts in evaluation and management of wounds, particularly chronic and complex wounds. However, the extent of direct involvement of plastic surgeons in wound care centers is unclear. In this study, we sought to evaluate the presence of plastic surgeons and other specialties in wound care centers across all Northeastern states Connecticut, Delaware, District of Columbia, Maine, Maryland, Massachusetts, New Jersey, New York, New Hampshire, Pennsylvania, Rhode Island, Virginia, West Virginia, and Vermont.

Methods
A comprehensive list of wound care clinics in northeastern United States was obtained from the Healogics website. For each site, information was gathered via website listings, including number of providers and the professional certification/specialization for each provider. Providers were those with qualifications including Doctor of Medicine (MD), Doctor of Osteopathic Medicine (DO), Doctor of Physical Therapy (DPT), Doctor of Podiatric Medicine (DPM), Certified Registered Nurse Anesthetist (CRNA), Certified Registered Nurse Practitioner (CRNP), Physician Associate (PA), and Physical Therapist (PT).

Results
A total of 118 Healogics wound care clinics and 492 providers were located across 14 northeastern states including District of Columbia. After researching each location, updated in November 2022, plastic surgeons were only 3.7% (18 of 492) providers employed. Specialties such as internal medicine (90 of 492 [18%]), general surgery (76 of 492 [15%]), podiatry (68 of 292 [13.8% ]), and other midlevel providers such as nurse practitioners (35 of 492 [7.1%]) were more frequently employed over plastic surgery. All plastic surgeons were board certified the American Board of Plastic Surgery.

Conclusions
Wound care requires collaboration between specialties, with significant repercussions on health care costs and patient outcomes. Plastic surgery provides unique surgical services for the healing of wounds, and the natural expectation would be that plastic surgery should be heavily involved at wound care centers. However, the data do not reflect significant involvement at an official level. Further studies will investigate causes and the societal, financial, and patient impacts of this lack of direct engagement. Although many plastic surgeons may not desire the majority of their practice to be wound care management, it stands to reason that some affiliation, at least for patient awareness and referral, may be warranted.
Cost-effectiveness of a purpose-built ward environment and new allied health model of care for major trauma
Authors: Gabbe Belinda J. , Reeder Sandra , Ekegren Christina L. , Mather Anne , Kimmel Lara , Cameron Peter A. , Higgins Alisa M. 
Published: March 2023

BACKGROUND
Targeted rehabilitation within the acute inpatient setting could have a substantial impact on improving outcomes for major trauma patients. The aim of this study was to investigate the cost-effectiveness of the introduction of a purpose-built ward environment, and a new allied health model of care (AHMOC) delivered in the acute inpatient setting, in a major trauma population.

METHODS
The statewide trauma registry, the trauma center's data warehouse, and electronic medical record data were used for this observational study. There were three phases: baseline, new ward, and new AHMOC. Cost-effectiveness was measured as cost per quality-adjusted life year using preinjury, hospital discharge, 1-month and 6-month 5-level, EQ-5D utility scores. Total costs included initial acute and inpatient rehabilitation care, as well as outpatient, readmission and ED presentations to 6-months.

RESULTS
Four hundred eleven patients were included. Case-mix was stable between phases. The median (IQR) number of allied health services received by patients was 8 (5–17) at baseline, 10 (5–19) in the new ward phase, and 17 (9–23) in the AHMOC phase. The proportion discharged to rehabilitation was 37% at baseline, 45% with the new ward and 28% with the new AHMOC. Mean (SD) total Australian dollar costs were $69,335 ($141,175) at baseline, $55,943 ($82,706) with the new ward and $37,833 ($49,004) with the AHMOC. The probability of the AHMOC being cost-effective at a willingness-to-pay threshold of $50,000 per quality-adjusted life year was 99.4% compared with baseline and 98% compared with the new ward.

CONCLUSION
The new allied health model of care was found to be a cost-effective intervention. Uptake of this model of allied health care at other trauma centers has the potential to reduce the cost and burden of major trauma.

LEVEL OF EVIDENCE
Economic and Value-based Evaluations; Level III.
Paeoniflorin protects 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s disease mice by inhibiting oxidative stress and neuronal apoptosis through activating the Nrf2/HO-1 signaling pathway
Authors: Zhang Jingyan , Bai Qingyang , Wen Qiuting , Han Lijun , Shi Yan , Zhang Xiaojie 
Published: March 2023

Objectives
This study aimed to explore the neuroprotective effects of paeoniflorin on oxidative stress and apoptosis in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) mice.

Methods
The effects of paeoniflorin on motor function in mice were evaluated by behavioral test. Then substantia nigra of mice were collected and neuronal damage was assessed using Nissl staining. Positive expression of tyrosine hydroxylase (TH) was detected by immunohistochemistry. Levels of malondialdehyde, superoxide dismutase (SOD) and glutathione were measured by biochemical method. terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay was used to detect apoptosis of dopaminergic neurons. Western blotting and real-time fluorescence quantitative PCR were used to detect the protein and mRNA expressions of Nrf2, heme oxygenase-1 (HO-1), B-cell lymphoma-2(Bcl-2), Bax and cleaved caspase-3.

Results
Paeoniflorin treatment significantly ameliorated the motor performance impairment in MPTP-induced PD mice. Moreover, it notably increased the positive expression rate of TH and reduced the damage and apoptosis of dopaminergic neurons in the substantia nigra. Furthermore, paeoniflorin increased the levels of SOD and glutathione and decreased the malondialdehyde content. It also promoted Nrf2 nuclear translocation, increased the protein and mRNA expressions of HO-1 and Bcl-2 and reduced the protein and mRNA expressions of BCL2-Associated X2 (Bax) and cleaved caspase-3. Treatment with the Nrf2 inhibitor, ML385, notably reduced the effects of paeoniflorin in MPTP-induced PD mice.

Conclusions
Neuroprotective effects of paeoniflorin in MPTP-induced PD mice may be mediated via inhibition of oxidative stress and apoptosis of dopaminergic neurons in substantia nigra through activation of the Nrf2/HO-1 signaling pathway.
Melanotransferrin Functions as a Pro-Oncogenic WNT Agonist: A Yin-Yang Relationship in Melanoma with the WNT Antagonist and Metastasis Suppressor, NDRG1
Authors: Paluncic J. , Gholam Azad M. , Lane D.J.R , Skoda J. , Park K.C. , Chiang S. , Bae D.H. , Scolyer R. , Afroz R. , Babu G. , Wilmott J. , Loh K. , Jansson P.J. , Dharmasivam M. , Huang M.L. , Zhao X. , Kovacevic Z. , Richardson D.R. 
Published: March 2023

AbstractA persistent mystery in the melanoma field has been the function of one of the first melanoma tumor antigens characterized, namely p97 (melanotransferrin; MTf). While MTf expression increases melanoma cell proliferation, migration, and tumorigenesis, the molecular mechanism responsible is unknown. On the other hand, N-myc down-stream regulated gene 1 (NDRG1) is a potent metastasis suppressor and WNT antagonist. Expression of NDRG1 in melanoma cells suggests a role in inhibiting metastasis, with this study investigating MTf’s role in oncogenic signaling. We demonstrate MTf acts as a pro-oncogenic WNT agonist, which down-regulates NDRG1, while silencingMTfincreases NDRG1 expression. In contrast, silencingNDRG1increases MTf expression. These observations demonstrate a bidirectional negative feedback loop and “Yin-Yang” relationship between MTf and NDRG1. Mechanistically, MTf was directly associated with the WNT co-receptor, lipoprotein-receptor 6 (LRP6), and increased total LRP6 expression, activated p-LRP6 (Ser1490), β-catenin, and activated β-catenin (Ser552) levels, with MTf expression inducing their nuclear accumulation. Additionally, MTf expression increased downstream WNT targets, namely cyclin D1 and c-Myc, with c-Myc down-regulating NDRG1 expression. Silencingc-Mycprevented the Yin-Yang relationship between NDRG1 and MTf, indicating c-Myc played a key role in their inverse regulation. Melanoma patient specimens demonstrated that a low NDRG1/MTf ratio was significantly (p= 0.008) associated with lower survival and metastasis. Chemotherapeutic agents that up-regulated NDRG1 depressed MTf and nuclear LRP6 and potently inhibited melanoma xenograft growthin vivo. This study demonstrates MTf acts as a WNT agonist, with a Yin-Yang relationship being observed with the WNT antagonist, NDRG1.
Zbtb46coordinates angiogenesis and immunity to control tumor outcome
Authors: Kabir Ashraf Ul , Subramanian Madhav , Wu Jun , Kim Minseo , Krchma Karen , Wang Xiaoli , Halabi Carmen M. , Pan Hua , Wickline Samuel A. , Fremont Daved H. , Choi Kyunghee 
Published: March 2023

AbstractTumor-angiogenesis and -immunity play critical roles in cancer progression and outcome. An inverse correlation of these two1hints at common regulatory mechanism(s). Here, we report thatZbtb46, a repressive transcription factor and a widely accepted marker for classical dendritic cells (DCs)2, 3, constitutes one such regulatory mechanism.Zbtb46was downregulated in both DCs and endothelial cells (ECs) by tumor-derived factors to facilitate robust tumor growth.Zbtb46downregulation led to a hallmark pro-tumor microenvironment (TME), including dysfunctional vasculature and immunosuppressive cell accumulation. Analysis of cancer patient data revealed a similar association of lowZBTB46expression with an immunosuppressive TME and a worse prognosis. In contrast, enforcedZbtb46expression mitigated the pro-tumor TME features and restricted tumor growth. Mechanistically,Zbtb46-deficient ECs were highly angiogenic, andZbtb46-deficient bone-marrow progenitors upregulatedCebpband diverted the DC program to myeloid lineage output, potentially explaining the myeloid lineage skewing phenomenon in cancer4–7. Conversely, enforcedZbtb46expression normalized tumor vessels and, by suppressingCebpb, skewed bone-marrow precursors towards more DC generation over macrophages, leading to an immune-hot TME. Remarkably,Zbtb46mRNA treatment synergized with anti-PD1 immunotherapy to improve tumor management in pre-clinical models. These findings identifyZbtb46as a common regulatory mechanism for angiogenesis and for myeloid lineage skewing in cancer and suggest that maintaining its expression could have therapeutic benefits.
A truncated HIV Tat demonstrates potent and specific latency reversal activity
Authors: Gulck Ellen Van , Pardons Marion , Nijs Erik , Verheyen Nick , Dockx Koen , Van den Eynde Christel , Battivelli Emilie , Vega Jerel , Florence Eric , Autran Brigitte , Archin Nancie M. , Margolis David M. , Katlama Kristine , Hamimi Chiraz , Van den Wyngaert Ilse , Eyassu Filmon , Vandekerckhove Linos , Boden Daniel 
Published: March 2023

ABSTRACTA major barrier to HIV-1 cure is caused by the pool of latently infected CD4 T-cells that persist under combination antiretroviral therapy (cART). This latent reservoir is capable of producing replication-competent infectious virus once prolonged suppressive cART is withdrawn. Inducing the reactivation of HIV-1 gene expression in T-cells harboring a latent provirus in people living with HIV-1 under cART will likely result in depletion of this latent reservoir due to cytopathic effects or immune clearance. Studies have investigated molecules that reactivate HIV-1 gene expression but to date no latency reversal agent has been identified to eliminate latently infected cells harboring replication-competent HIV in cART treated individuals. Stochastic fluctuations in HIV-1tatgene expression have been described and hypothesized to allow the progression into proviral latency. We hypothesized that exposing latently infected CD4+ T-cells to Tat would result in effective latency reversal. Our results indicate the capacity of a truncated Tat protein and mRNA to reactivate HIV-1 in latently infected T-cellsex vivoto a similar degree as the protein kinase C agonist: Phorbol 12-Myristate 13-Acetate, without T-cell activation nor any significant transcriptome perturbation.
Effectiveness of a multi-country implementation-focused network on quality of care: delivery of interventions and processes for improved maternal, newborn and child health outcomes
Authors: Djellouli Nehla , Shawar Yusra Ribhi , Mwaba Kasonde , Akter Kohenour , Seruwagi Gloria , Tufa Asebe Amenu , Gonfa Geremew , Mwandira Kondwani ,   QCN Evaluation Group, Kyamulabi Agnes , Shiffman Jeremy , English Mike , Colbourn Tim 
Published: March 2023

AbstractThe Network for Improving Quality of Care for Maternal, Newborn and Child Health (QCN) aims to work through learning, action, leadership and accountability. We aimed to evaluate the effectiveness of QCN in these four areas at the global level and in four QCN countries: Bangladesh, Ethiopia, Malawi and Uganda.This mixed method evaluation comprised 2-4 iterative rounds of data collection between 2019-2022, involving stakeholder interviews, hospital observations, QCN members survey, and document review. Qualitative data was analysed using a coding framework developed from underlying theories on network effectiveness, behaviour change, and QCN proposed theory of change. Survey data capturing respondents’ perception of QCN was analysed with descriptive statistics.The QCN global level, led by the WHO secretariat, was effective in bringing together network countries’ governments and global actors via providing online and in-person platforms for communication and learning. In-country, various interventions were delivered in ‘learning districts’, however often separately by different partners in different locations, and disrupted by the pandemic. Governance structures for quality of care were set-up, some preceding QCN, and were found to be stronger and better (though often externally) resourced at national than local levels. Awareness of operational plans and network activities was lower at local than national levels but increased from 2019 to 2022. Capacity building efforts were implemented – yet often dependent on implementing partners and donors. QCN stakeholders agreed 15 core monitoring indicators though data collection was challenging, especially for indicators requiring new or parallel systems including those on experience of care. Accountability through community engagement, scorecards, and ombudsmen was encouraged but these initiatives remained nascent in 2022.Global and national leadership elements of QCN have been most effective to date, with action, learning and accountability more challenging, partner or donor dependent, remaining to be scaled-up, and pandemic-disrupted.
Brain-wide mapping of neuronal architecture controlling torpor
Authors: Yamaguchi Hiroshi , Murphy Keith R , Fukatsu Noriaki , Sato Kazuhide , Yamanaka Akihiro , de Lecea Luis 
Published: March 2023

AbstractEndotherms can survive low temperatures and food shortage by actively entering a hypometabolic state known as torpor. Although the decrease in metabolic rate and body temperature during torpor is controlled by the brain, the underlying neural circuits remain largely unknown. In this study, we identify the neural circuits involved in torpor regulation by combining whole-brain mapping of torpor-activated neurons, cell type-specific manipulation of neural activity, and viral tracing-based circuit mapping. We found that Trpm2-positive neurons in the preoptic area and Vgat-positive neurons in the dorsal medial hypothalamus are activated during torpor. Genetic silencing shows the activity of either cell type is necessary to enter the torpor state. Finally, we show that these cells receive projections from the arcuate and suprachiasmatic nucleus and send projections to brain regions involved in thermoregulation. Our results demonstrate an essential role of hypothalamic neurons in the regulation of body temperature and metabolic rate during torpor and identify critical nodes of the torpor-regulatory network.
Interaction Between HCN and Slack Channels Regulates mPFC Pyramidal Cell Excitability and Working Memory
Authors: Wu Jing , El-Hassar Lynda , Datta Dibyadeep , Thomas Merrilee , Zhang Yalan , David P. Jenkins , DeLuca Nicholas J. , Chatterjee Manavi , Gribkoff Valentin K. , Arnsten Amy F.T. , Kaczmarek Leonard K. 
Published: March 2023

AbstractThe ability of monkeys and rats to carry out spatial working memory tasks has been shown to depend on the persistent firing of pyramidal cells in the prefrontal cortex (PFC), arising from recurrent excitatory connections on dendritic spines. These spines express hyperpolarization-activated cyclic nucleotide-gated (HCN) channels whose open state is increased by cAMP signaling, and which markedly alter PFC network connectivity and neuronal firing. In traditional neural circuits, activation of these non-selective cation channels leads to neuronal depolarization and increased firing rate. Paradoxically, cAMP activation of HCN channels in PFC pyramidal cells reduces working memory-related neuronal firing. This suggests that activation of HCN channels may hyperpolarize rather than depolarize these neurons. The current study tested the hypothesis that Na+influx through HCN channels activates Na+-activated K+(KNaor Slack) channels to hyperpolarize the membrane. We have found that HCN and Slack KNachannels co-immunoprecipitate in cortical extracts and that, by immunoelectron microscopy, they colocalize at postsynaptic spines of PFC pyramidal neurons. A specific blocker of HCN channels, ZD7288, reduces KNacurrent in pyramidal cells that express both HCN and Slack channels, indicating that blockade of HCN channels reduced K+current indirectly by lowering Na+influx. In contrast, ZD7288 has no effect on KNacurrents in an HEK cell line stably expressing this Slack channels but no HCN channels, demonstrating that ZD7288 does not block Slack channels directly. Activation of HCN channels by cAMP in a cell line expressing a Ca2+reporter results in elevation of cytoplasmic Ca2+, but the effect of cAMP is completely reversed if the HCN channels are co-expressed with Slack channels. Finally, we have used a novel pharmacological blocker of Slack channels to show that inhibition of either Slack or HCN channels in rat PFC improves working memory performance, and that the actions of Slack and HCN channel blockers occlude each other in the memory task. Our results suggest that the regulation of working memory by HCN channels in PFC pyramidal neurons is mediated by an HCN-Slack channel complex that links activation HCN channels to suppression of neuronal excitability.