bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarker associations with insomnia and secondary sleep outcomes in persons with and without HIV in the POPPY-Sleep substudy: a cohort study
Authors: Bakewell Nicholas , Sabin Caroline A , Negi Riya , Garcia-Leon Alejandro , Winston Alan , Sachikonye Memory , Doyle Nicki , Redline Susan , Mallon Patrick W G , Kunisaki Ken M 
Published: September 2022

AbstractStudy ObjectivesWe investigated associations between inflammatory profiles/clusters and sleep measures in people living with HIV and demographically-/lifestyle-similar HIV-negative controls in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY)-Sleep substudy.MethodsPrimary outcome was insomnia (Insomnia Severity Index [ISI]&gt;15). Secondary sleep outcomes included 7-day actigraphy (e.g. mean/standard deviation of sleep duration/efficiency), overnight oximetry (e.g. oxygen desaturation index [ODI]) and patient-reported measures (Patient-Reported Outcomes Measurement Information System (PROMIS) sleep questionnaires). Participants were grouped using Principal Component Analysis of 31 biomarkers across several inflammatory pathways followed by cluster analysis. Between-cluster differences in baseline characteristics and sleep outcomes were assessed using Kruskal–Wallis/logistic regression/Chi-squared/Fisher’s exact tests.ResultsOf the 465 participants included (74% people with HIV, median [interquartile range] age 54 [50–60] years), only 18% had insomnia and secondary sleep outcomes suggested generally good sleep (e.g. ODI 3.1/hr [1.5–6.4]). Three clusters with distinct inflammatory profiles were identified: “gut/immune activation” (n = 47), “neurovascular” (n = 209), and “reference” (relatively lower inflammation; n = 209). The “neurovascular” cluster included higher proportions of people with HIV, obesity (BMI&gt;30 kg/m2), and previous cardiovascular disease, mental health disorder, and arthritis of knee/hip relative to the other two clusters. No clinically relevant between-cluster differences were observed in proportions with insomnia (17%, 18%, 20%) before (p = .76) or after (p = .75) adjustment for potential confounders. Few associations were observed among actigraphy, oximetry, and PROMIS measures.ConclusionsAlthough associations could exist with other sleep measures or biomarker types not assessed, our findings do not support a strong association between sleep and inflammation in people with HIV.
Treatment with Amniotic Fluid Stem Cell Extracellular Vesicles Promotes Fetal Lung Branching and Cell Differentiation at Canalicular and Saccular Stages in Experimental Pulmonary Hypoplasia Secondary to Congenital Diaphragmatic Hernia
Authors: Khalaj Kasra , Figueira Rebeca Lopes , Antounians Lina , Gandhi Sree , Wales Matthew , Montalva Louise , Biouss George , Zani Augusto 
Published: September 2022

Abstract
Pulmonary hypoplasia secondary to congenital diaphragmatic hernia (CDH) is characterized by impaired branching morphogenesis and differentiation. We have previously demonstrated that administration of extracellular vesicles derived from rat amniotic fluid stem cells (AFSC-EVs) rescues development of hypoplastic lungs at the pseudoglandular and alveolar stages in rodent models of CDH. Herein, we tested whether AFSC-EVs exert their regenerative effects at the canalicular and saccular stages, as these are translationally relevant for clinical intervention. To induce fetal pulmonary hypoplasia, we gavaged rat dams with nitrofen at embryonic day 9.5 and demonstrated that nitrofen-exposed lungs had impaired branching morphogenesis, dysregulated signaling pathways relevant to lung development (FGF10/FGFR2, ROBO/SLIT, Ephrin, Neuropilin 1, β-catenin) and impaired epithelial and mesenchymal cell marker expression at both stages. AFSC-EVs administered to nitrofen-exposed lung explants rescued airspace density and increased the expression levels of key factors responsible for branching morphogenesis. Moreover, AFSC-EVs rescued the expression of alveolar type 1 and 2 cell markers at both canalicular and saccular stages and restored markers of club, ciliated epithelial, and pulmonary neuroendocrine cells at the saccular stage. AFSC-EV-treated lungs also had restored markers of lipofibroblasts and PDGFRA+ cells to control levels at both stages. EV tracking showed uptake of AFSC-EV RNA cargo throughout the fetal lung and an mRNA-miRNA network analysis identified that several miRNAs responsible for regulating lung development processes were contained in the AFSC-EV cargo. These findings suggest that AFSC-EV-based therapies hold potential for restoring fetal lung growth and maturation in babies with pulmonary hypoplasia secondary to CDH.
The role of next-generation sequencing in acute myeloid leukemia
Authors: Llop Marta , Sargas Claudia , Barragán Eva 
Published: September 2022

Purpose of review
The development of high-throughput techniques like next-generation sequencing (NGS) has unraveled the genetic profile of cancer. In this review, we discuss the role of NGS on the diagnostic, risk stratification, and follow-up of patients with acute myeloid leukemia (AML).

Recent findings
NGS has become an essential tool in clinical practice for AML management. Therefore, efforts are being made to improve its applications, automation, and turnaround time. Other high-throughput techniques, such as whole genome sequencing or RNA-sequencing, can be also used to this end. However, not all institutions may be able to implement these approaches. NGS is being investigated for measurable residual disease (MRD) assessment, especially with the development of error-correction NGS. New data analysis approaches like machine learning are being investigated in order to integrate genomic and clinical data and develop comprehensive classifications and risk scores.

Summary
NGS has proven to be a useful approach for the analysis of genomic alterations in patients with AML, which aids patient management. Current research is being directed at reducing turnaround time and simplifying processes so that these techniques can be universally integrated into clinical practice.
Durable Responses in Patients With Advanced Cholangiocarcinoma on Sequential Dual-agent Immunotherapy After Progressing on Single-agent Immunotherapy
Authors: Kaakour Dalia , Hagopian Garo , Lee Sonia , Lee Fa Chyi 
Published: September 2022

Objectives:
Biliary tract tumors have a poor prognosis despite advancements in targeted therapies. More recent studies have started to investigate the use of combination immunotherapy in advanced biliary cancers. However, currently, there are no clinical trials investigating the use of dual-agent immunotherapy with ipilimumab and nivolumab as a sequential treatment after patients have progressed on single-agent immunotherapy. In this case series, we discussed 3 patients with advanced cholangiocarcinoma who have an objective response to dual-agent immunotherapy with ipilimumab and nivolumab after having disease progression on pembrolizumab and multiple other failed lines of treatment.

Materials and Methods:
A case series, including 3 patients treated at the University of California, Irvine Chao Family Comprehensive Cancer Center, was completed.

Results:
Although none of the 3 patients had microsatellite instability or high tumor-mutation burden and were not necessarily predicted to have a response to dual-agent immunotherapy, all 3 patients had an objective radiographic and/or tumor-marker response to a combination of ipilimumab and nivolumab.

Conclusions:
This case series serves as proof of the concept that sequential immunotherapy can be beneficial after progression on single-agent immunotherapy for patients with advanced cholangiocarcinoma. This study can also serve as the foundation to build further tests on the true effectiveness and ideal duration of sequential therapy with dual immunotherapy agents.
Simultaneous Contralateral Autologous Breast Augmentation during Unilateral Breast Reconstruction Utilizing Deep Inferior Epigastric Flaps
Authors: Gupta Rohun , John Jithin , Gupta Rushil , Hart Justin , DeSano Jeffrey , Sachanandani Neil S. , Chaiyasate Kongkrit 
Published: September 2022

Background:
It is predicted that 281,550 new cases of invasive breast cancer and 49,290 new cases of ductal carcinoma in situ will be diagnosed this year. In this study, we will detail our experience with simultaneous contralateral autologous breast augmentation during unilateral breast reconstruction utilizing bilateral deep inferior epigastric perforator (DIEP) flaps.

Methods:
A retrospective analysis of patients who underwent simultaneous contralateral autologous breast augmentation during unilateral breast reconstruction utilizing bilateral DIEP flaps by the senior surgeons at Beaumont Health Systems, Royal Oak, was conducted. Demographic data, operative details, complications, medical comorbidities, and patient outcomes were retrospectively analyzed.

Results:
Seven patients who met the inclusion criteria were identified. One patient underwent immediate reconstruction with DIEP flaps, one patient had a history of lumpectomy and underwent delayed partial breast reconstruction, three patients had delayed unilateral DIEP breast reconstruction with contralateral breast augmentation, and two patients had previous augmentations that were revised. All patients examined in this review tolerated the procedures well and had clinically viable flaps along with superior aesthetic outcomes.

Conclusions:
This technique can be applied to various clinical conditions, including immediate breast reconstruction, delayed breast reconstruction, and salvage for failed implant-based reconstruction, leading to optimal patient outcomes and satisfaction. Unilateral breast reconstruction with simultaneous contralateral autologous breast augmentation utilizing bilateral DIEP flaps is a surgical technique that more plastic surgeons should utilize.
Predictors of Success following Microvascular Replantation Surgery of the Upper Extremity in Adult Patients
Authors: Rizzo Kayla R. , Eckhoff Michael D. , Gonzalez Gilberto A. , Diamond Shawn , Nesti Leon , Dunn John C. 
Published: September 2022

Background:
The purpose of this study is to ascertain which factors are associated with successful replantation in the upper extremity. Secondarily, the purpose was to determine patient factors that differentiate those patients who undergo initial replantation versus initial amputation.

Methods:
Data gathered for this retrospective study were obtained from a custom subset of the 2015–2020 IBM Truven MarketScan Commercial and IBM Truven MarketScan Medicare Supplemental databases. Data were sorted using Current Procedural Terminology codes and International Classification of Disease, Ninth and Tenth Revision, diagnosis codes.

Results:
Increasing age was significantly associated with undergoing initial amputation compared with replantation (P < 0.001; 95% CI, 47.146–50.654). Among comorbid conditions, patients with diabetes mellitus type II (2.4% versus 24.3%; P < 0.001), hypertension (11.9% versus 28.0%; P = 0.03), end-stage renal disease (0% versus 10.5%; P = 0.03), and hypertensive chronic kidney disease (0% versus 8.7%; P = 0.04) more commonly underwent an initial amputation procedure. When evaluating the need for secondary procedure after replantation, there was no statistical significance between groups when comparing age, gender, insurance type, general comorbidities, connective tissue disorders, mental health disorders, or geographic location.

Conclusions:
In conclusion, this study demonstrates that age and the presence of comorbidities are important factors in the differentiation of which patients undergo initial reimplantation versus initial amputation. Additionally, no specific factors were identified that were associated with secondary procedures after replantation.
BCG Vaccine–associated Complications in a Large Cohort of Children With Combined Immunodeficiencies Affecting Cellular and Humoral Immunity
Authors: Al-Herz Waleed , Husain Entesar H. , Adeli Mehdi , Al Farsi Tariq , Al-Hammadi Suleiman , Al Kuwaiti Amna Ali , Al-Nesf Maryam , Al Sukaiti Nashat , Al-Tamemi Salem , Shendi Hiba 
Published: September 2022

Aims:
To present the details of Bacillus Calmette-Guérin (BCG)-vaccine associated complications (VACs) in combined immunodeficiencies (CID) patients.

Methods:
Five centers participated in this retrospective study and completed a data form, which included general patients’ information, clinical and laboratory data.

Results:
Among 236 CID patients, 127 were BCG vaccinated. 41.9% of patients with family history of CID and 17.1% who were diagnosed by screening were BCG vaccinated. Twenty-three patients (18.1%) developed BCG-VACs. The median age of VACs was 6 months and the median time from vaccination to complications was 6 months. The highest rate of BCG-VACs was recorded in patients receiving the Russian BCG strain compared to the Tokyo and Danish strains. Univariate analysis of T-lymphocyte subsets showed increased odds of BCG complications in patients with CD3+, CD4+, and CD8+ counts of ≤250 cells/µL. Only CD8 + count ≤250 cells/µL had increased such odds on multivariate analysis. VACs were disseminated in 13 and localized in 10 patients. Localized complication occurred earlier after vaccination (median: 4 months) compared with disseminated ones (median: 7 months). There were no significant associations between sex, administered vaccine strain, serum immunoglobulins levels, lymphocyte subsets counts, and the chance of having either localized or disseminated BCG-related complications.

Coclusions:
Although contraindicated, many patients with CID continue to be vaccinated with BCG. Low CD8 + count is a risk factor for BCG–related complications and localized complications occurred earlier than disseminated ones. Considerations should be undertaken by health care authorities especially in countries with high incidence of CID to implement newborn screening, delay the time of BCG vaccine administration beyond 6 months of age and to use the relatively safer strains like the Danish and Tokyo ones.
Disparities in Diagnosis and Treatment of Cervical Adenocarcinoma Compared With Squamous Cell Carcinoma: An Analysis of the National Cancer Database, 2004–2017
Authors: Smith Anna Jo Bodurtha , Beavis Anna L. , Rositch Anne F. , Levinson Kimberly 
Published: September 2022

Objectives
The aim of the study are to compare trends in diagnosis and treatment of adenocarcinoma of the cervix (AC) to squamous cell carcinoma of the cervix (SCC) and to examine associations between stage at diagnosis and guideline-concordant treatment with race, age, and insurance type for AC and SCC.

Materials and Methods
We performed a retrospective cohort study of cervical AC (n = 18,811) and SCC (n = 68,421) from the 2004–2017 National Cancer Database. We used generalized linear models to evaluate trends in frequency of histologies and to evaluate associations between race, age, and insurance status with stage of diagnosis and receipt of National Comprehensive Cancer Network guideline–concordant treatment for AC and SCC.

Results
The proportion of AC relative to SCC increased from 19.4% (95% CI = 18.4–20.5) to 23.2% (95% CI = 22.2–24.2) from 2004 to 2017 (p < .001). Compared with SCC, women with AC were younger, more likely to be White, and privately insured (p < .001). Older women with AC were 44% less likely to be diagnosed with early-stage disease than younger women (adjusted relative risk = 0.56, 95% CI = 0.52–0.60); there was no significant difference for SCC. Black women with AC were 16% less likely to be diagnosed with early-stage disease (adjusted relative risk [aRR] = 0.84, 95% CI = 0.79–0.89) than White women. Women with public insurance were less likely to be diagnosed at an early stage for both AC (aRR = 0.81, 95% CI = 0.78–0.84) and SCC (aRR = 0.79, 95% CI = 0.77–0.81). Rates of guideline-concordant treatment were similar for AC and SCC, with minimal differences by age, race, and insurance.

Conclusions
As the proportion of AC to SCC rises, important race and age-related disparities must be addressed to reduce unnecessary morbidity and death.
Updates in the use of cannabis for insomnia
Authors: Earl David C. , Proano Marco 
Published: September 2022

Purpose of review
This review aims to summarize recent updates in the area of cannabis use for insomnia.

Recent findings
Cannabis products have continued to become more potent, particularly in regard to delta-9- tetrahydrocannabinol (THC) concentration. Additionally, the use of cannabis has continued to become more accepted with less legal restrictions. The reported use of cannabis for relief of symptoms in sleep disorders appears to be increasing, however the specific effects of cannabinoids on sleep varies with cannabinoid type and concentration. Some evidence supports claims of efficacy of cannabinoids in sleep disorders such as insomnia, while other evidence is either lacking or in some cases contradictory. Regular cannabis use has been associated with withdrawal which can profoundly alter sleep. Also, clinicians should be aware of the potential effects of cannabis on the metabolism of other medications as well as the fact that cannabis use has been reported in a significant number of women in the periods before, during, and after pregnancy.

Summary
Cannabis use has been becoming more and more prevalent in the setting of relaxed restrictions and easier consumer level access to cannabis and cannabis products. A relative paucity of high quality evidence regarding the effects of cannabis on sleep and the treatment of insomnia symptoms remains. The optimal type, concentration, ratio, and dosage form of cannabinoids in the treatment of insomnia symptoms needs further clarification. As the trend of acceptance and use of cannabis continues, more high quality evidence to help guide clinicians in their recommendations will hopefully become available.
The role of surgery for loco-regional and advanced urological cancers
Authors: Chow Kit Mun , Tay Kae Jack , Yuen John , Chen Kenneth 
Published: September 2022

Purpose of review
There is a general misconception that surgery is the antithesis of palliation. However, symptom mitigation, the basic tenet of palliative interventions, can be achieved by invasive procedures. Surgical care, thus, plays an important role in palliative oncology, alongside radiation and systemic therapy. There is global movement to improve palliation in oncology, and thus it is timely to evaluate the role of surgical interventions can play in this setting.

Recent findings
Many of the surgical interventions done with palliative intent were first established as curative options. Most studies looked at interventions for local control of primary tumour including extirpative surgeries, while some studies studied pain relief for bone metastases. Results show that patients have an acceptable survival outcome and complication rate comparable to those done in the curative setting. However, not all studies report functional outcomes and symptom-relief consistently, highlighting an unmet need.

Summary
More studies are needed to further define the role of surgery in palliative care. Randomized controlled trials studying surgical intervention in the palliative setting will be challenging because of lack of equipoise, inherent bias in patient and disease characteristics in those who undergo surgery. Nonetheless, studies should endeavour to study symptom-free survival and PROMs as meaningful endpoints of interventions performed in a palliative setting rather than solely focus on hard oncological endpoints of survival.
Nipple-Sparing Mastectomy and Immediate Implant-Based Breast Reconstruction: A Propensity Score Matched Analysis of Satisfaction and Health Related Quality of Life
Authors: Kokosis George , Stern Carrie S. , Shamsunder Meghana G. , Polanco Thais O. , Patel Vaidehi M. , Slutsky Hanna , Morrow Monica , Moo Tracy-Ann , Sacchini Virgilio , Coriddi Michelle , Cordeiro Peter G. , Matros Evan , Pusic Andrea , Disa Joseph J. , Mehrara Babak J. , Nelson Jonas A. 
Published: September 2022

Background:
Although it is intuitive that nipple-sparing mastectomy (NSM) in selected patients would result in excellent cosmetic outcomes and high patient satisfaction, studies of clinical outcomes and health-related quality of life (HRQOL) are limited and show mixed results. This study aimed to use a propensity score matching analysis to compare satisfaction and HRQOL outcomes in patients who underwent implant-based reconstruction following bilateral NSM or skin-sparing mastectomy (SSM).

Methods:
A propensity score matching analysis (1:1 matching, no replacement) was performed comparing patients undergoing NSM or SSM with immediate bilateral implant-based breast reconstruction. Patients with a history of any radiation therapy were excluded. Matched covariates included age, BMI, race, smoking history, neoadjuvant chemotherapy, bra size, and history of psychiatric diagnosis. Outcomes of interest included BREAST-Q scores and complications.

Results:
We examined 1371 patients for matching and included 460 patients (230 NSM and 230 SSM) in the final analyses. We found no significant differences in baseline, cancer, and surgical characteristics between matched NSM and SSM patients, who also had similar profiles for surgical complications. Interestingly, we found that postoperative satisfaction-with-breast scores and all other HRQOL domains were stable over a 3-year period and did not significantly differ between the two groups.

Conclusion:
Compared with SSM, bilateral NSM did not improve patient-reported or clinical outcomes when combined with immediate implant-based reconstruction. The impact that NSM may have on breast aesthetics and the ability of the BREAST-Q to gauge an aesthetic result following NSM warrant further investigation.
Comparing Breast Sensation between Alloplastic and Autologous Breast Reconstruction Patients using the BREAST-Q Sensation Module
Authors: Voineskos Sophocles H. , Olaiya Oluwatobi R. , Tsangaris Elena , Kaur Manraj , Klassen Anne F. , Pusic Andrea L. 
Published: September 2022

Background:
Sensory recovery of the breast is a compelling frontier in comprehensive post-mastectomy breast reconstruction. This study uses the BREAST-Q Sensation Module to evaluate the differences in women who underwent an alloplastic versus autologous breast reconstruction.

Methods:
Women with a history of breast cancer and post-mastectomy breast reconstruction were recruited through the Love Research Army, United States. Participants completed the BREAST-Q Sensation Module (3 scales: Breast Symptoms, Breast Sensation, Quality of Life Impact). Descriptive statistics and multiple linear regression analyses were used to compare outcomes between women undergoing alloplastic or autologous breast reconstruction.

Results:
Of 1204 respondents, 933 were included for analysis, 620 (66.5%) underwent alloplastic reconstruction and 313 (33.5%) underwent autologous reconstruction. The average age and BMI were 59.2 years (±10.1) and 26 (±5) respectively. Autologous reconstruction patients scored an average of 6.1 points (95% CI 3.9-8.4, p<0.001) and 5.3 points (95% CI 2.5-8.1, p=0.001) higher on the Breast Symptoms and Quality of Life Impact scales, respectively. No difference (0.0 points, 95% CI -2.9-3.0, p=0.75) was observed for the Breast Sensation scale. Increased time since reconstruction had a positive impact on Breast Symptoms scores. Radiotherapy negatively affected scores on both Breast Symptoms and Quality of Life Impact scales.

Conclusions:
Autologous breast reconstruction may be associated with fewer abnormal breast sensations and better sensation-related quality of life in comparison to alloplastic reconstruction. This information can be incorporated during preoperative patient counseling when discussing reconstructive options.