bluuebunny/crossref_metadata_2025_split huggingface dataset:
Galactagogues and Lactation
Authors: Balkam Jane J. 
Published: January 2022

Abstract
Development of a milk supply is a complex process that is not always understood by women who are breastfeeding. Galactagogues are substances commonly used by breastfeeding women who perceive that they have an insufficient milk supply. They can be herbal substances or pharmaceuticals. Herbal galactagogues are advertised and sold to women as capsules, cookies, milk shakes, and teas, as well as other forms of herbal supplements. Herbal galactagogues are classified as dietary supplements and not reviewed or regulated by the U.S. Food and Drug Administration. There are limited data on their safety and efficacy. Women experiencing problems with their milk supply should receive a thorough and thoughtful assessment of the situation. There are many factors that should be considered when counseling breastfeeding women about use of galactagogues. The physiology of lactation, process of milk supply development, and the evidence for use of galactagogues are reviewed to add to the knowledge of nurses and other health care providers working with women who are breastfeeding.
Prevalence of and Theoretical Explanation for Type 2 Benign Paroxysmal Positional Vertigo
Authors: Harmat Kinga , Tamás László T. , Schubert Michael C. , Gerlinger Imre , Komoly Sámuel , Büki Béla 
Published: January 2022

Background and Purpose:
A variant of benign paroxysmal positional vertigo (BPPV) involves the subjective report of vertigo without the coinciding nystagmus. This presentation includes truncal retropulsion when sitting up from the ipsilesional provocative test (ie, Dix-Hallpike), which we term type 2 BPPV. The primary objective of this study is to prospectively determine the prevalence and describe the clinical course of type 2 BPPV. We offer a theoretical explanation for the absence of nystagmus.

Methods:
Prospective, observational study carried out in 2 tertiary hospitals. One hundred eighty patients (134 women, 46 men) met the inclusion criteria and were included between January 10, 2018, and October 30, 2019. Efficacy of physical therapy maneuvers was determined at 1-week follow-up. Three-dimensional reconstructions of the planes of the semicircular canal cupula from histological preparations are offered as evidence for the theoretical explanation.

Results:
One-third of the patients met the criteria for type 2 BPPV; the remainder had typical posterior or horizontal semicircular canal involvement. Symptoms from type 2 BPPV were longer in duration yet responded favorably to physical therapy maneuvers. Upon repeat testing, 19 patients treated for posterior canalithiasis developed a slight, persistent positional downbeat nystagmus in the Dix-Hallpike position that we propose as evidence the otoconia entered the short arm of the posterior semicircular canal.

Discussion and Conclusions:
Our data and 3-dimensional rendering suggest the report of vertigo, yet absent nystagmus in type 2 BPPV is from otoconia aligning with the gravitoinertial vector during provocative testing that precludes cupular stimulation. Type 2 BPPV appears to be a common and treatable form of vertigo.

Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A372).
0.45% Versus 0.9% Saline in 5% Dextrose as Maintenance Fluids in Children Admitted With Acute Illness
Authors: Ratnjeet Kumar , Pallavi Pallavi , Jhamb Urmila , Saxena Romit 
Published: January 2022

Background
The safety of giving intravenous (IV) maintenance fluids according to Holliday and Segar's recommendations of 1957 has recently been questioned after reports of complications caused by iatrogenic hyponatremia in children receiving hypotonic fluids. However, the current practice of choice of maintenance IV fluids for hospitalized children varies worldwide. This study was planned to compare 0.45% and 0.9% saline in 5% dextrose at standard maintenance rates in hospitalized children aged 3 months to 12 years.

Objective
Primary objective was to study change in serum sodium level at 24 hours in children receiving total IV fluid maintenance therapy as 0.45% or 0.9% normal saline in 5% dextrose. Secondary objectives of this study were to estimate change in serum sodium levels from the baseline to 48 or 72 hours, if IV fluids were continued, and to find incidence of hyponatremia and hypernatremia after administering these 2 types of maintenance fluids.

Methods
This study was an open-label, randomized control trial conducted at the Department of Pediatrics of a tertiary care hospital from July 22, 2019, to October 28, 2019. Two hundred children aged 3 months to 12 years admitted in pediatric emergency and requiring IV maintenance fluid were randomized into 2 groups (group A received 0.45% saline in 5% dextrose, group B received 0.9% normal saline in 5% dextrose) with 100 in each group.

Results
Both groups were comparable for baseline characteristics. Fall in mean serum sodium from baseline was more with increasing duration of IV fluids until 24 hours in 0.45% saline group as compared with 0.9% saline group, which was statistically significant (P < 0.001). The incidence of mild and moderate hyponatremia was significantly more in hypotonic group at 12 hours (P < 0.001) and 24 hours (P < 0.001). However, there was no significant difference at 48 hours.

Conclusions
The fall in serum sodium values was significant, and there was significant risk of hyponatremia with the use of hypotonic fluids at 12 and 24 hours. Hence, the use of isotonic fluids seems to be more appropriate among the hospitalized children.
Trial Registration: CTRI/2019/10/021791.
Endoscopic Approach in the Diagnosis of Gastrointestinal Acute Graft Versus Host Disease in Children
Authors: Faraci Maura , Giardino Stefano , Madeo Annalisa , Coccia Cristina , Arrigo Serena , Pierri Filomena , Gandullia Paolo 
Published: January 2022

Objectives:
The objectives of this study were to describe clinical, histological, and endoscopic findings in children undergoing gastrointestinal (GI) endoscopy for symptoms of digestive acute graft-versus-host disease (a-GvHD), to evaluate the rate of steroid-resistant GvHD and transplant-related mortality, and to describe the feasibility and safety of the endoscopic procedure.

Methods:
This was a retrospective study conducted, at the IRCSS Istituto G. Gaslini in Genova, Italy, in 26 children undergoing upper or lower GI endoscopy after allogeneic hematopoietic stem cell transplantation between 2000 and 2017.

Results:
Histology confirmed a diagnosis of a-GvHD in 73% of patients; it was frequently associated with steroid-resistant a-GvHD (P = 0.001) and with an increased transplant-related mortality. Additionally, one patient developed duodenal hematoma after endoscopy for a high-grade GI a-GvHD.

Conclusions:
In our experience, the endoscopic approach in the diagnosis of GI a-GvHD in children was feasible and safe. Furthermore, the histological diagnosis of GI a-GvHD was associated with an increased risk of steroid-resistant GvHD and with high transplant-related mortality.
Are Perforators Reliable as Recipient Arteries in Lower Extremity Reconstruction? Analysis of 423 Free Perforator Flaps
Authors: Power Hollie A. , Cho Jeongmok , Kwon Jin Geun , Abdelfattah Usama , Pak Changsik John , Suh Hyunsuk Peter , Hong Joon Pio 
Published: January 2022

Background:
Perforator flaps have revolutionized lower limb reconstruction by offering single-stage thin, pliable coverage with an excellent aesthetic match. Although anastomosis of the flap to a major artery remains the gold standard, perforator-to-perforator anastomosis has several advantages, including expedient recipient dissection and increased recipient options in vessel-depleted extremities. The aim of this study was to compare flap survival when a perforator or major artery was used as a recipient vessel.

Methods:
A retrospective cohort of free perforator flaps for lower limb reconstruction was reviewed. Demographics, comorbidities, vascular status, defect characteristics, operative details, and complications were recorded. Outcomes for perforator and major artery recipients were compared.

Results:
Four hundred twenty-three flaps were performed for various reasons using perforator flaps. The total limb salvage rate was 98.8 percent. Total and partial flap failure rates were 6.1 percent and 9.0 percent, respectively. Comparing perforator recipients [n = 109 (25.8 percent)] to major artery recipients [n = 314 (74.2 percent)], there was no significant difference in total (p = 0.746) or partial flap failure (p = 0.212). Significant factors between the groups included larger flap size with major artery recipients (p = 0.001) and shorter operative time when using a perforator recipient (p = 0.012)

Conclusions:
Perforator-to-perforator anastomosis is a reliable option that affords equivalent rates of flap success compared to major artery anastomosis in lower extremity reconstruction. The authors advocate using a major artery recipient in defects where the axial vessels are easily accessible. A perforator recipient is a viable alternative in defects where access to the axial vessels is inconvenient and in patients with limited recipient options.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
68Ga-DOTA-FAPI-04 Uptake of Accessory Breast in a Patient With Breast Cancer
Authors: Xu Tingting , Wang Wei , Yang Chuan , Cai Liang , Chen Yue 
Published: January 2022

Abstract

68Ga-DOTA-FAPI-04 is a promising PET agent for tumor imaging. However, some nonneoplastic lesions can also show increased FAPI uptake. Herein, we presented a case of a patient with left breast cancer who showed a right accessory breast with increased tracer uptake on 68Ga-DOTA-FAPI-04 PET/CT. Final histopathology confirmed there were no malignant components in the accessory breast.
Factors Associated With Mortality Among Patients Managed for Large Volume Hemorrhage in a Medical Intensive Care Unit
Authors: Dettmer Matthew , Morrison James , Bari Vase , Krishnan Sudhir , Wang Xiaofeng , Li Manshi , Duggal Abhijit , Adams Gregory , Hite Duncan 
Published: January 2022

ABSTRACT

Purpose:
Our goal was to describe resuscitation practices in critically ill medical patients with active hemorrhage requiring large volume resuscitation and identify factors associated with poor outcomes.

Patients and Methods:
This was a single center retrospective observational cohort study. Patients admitted to the medical intensive care unit from 2011 to 2017 who received ≥5 units of packed red blood cells (pRBCs) within 24 h were included. Data including volume of blood products and crystalloid administered, baseline sequential organ failure assessment (SOFA) scores, and outcomes were abstracted. Univariate and multivariate analyses were performed to determine clinical factors associated with hospital mortality.

Results:
Two hundred forty-six patients were identified. Mean volumes of 2,448 mL of pRBCs and 3.9L of crystalloid were transfused over 24 h. Inpatient mortality for the entire cohort was 48%. Multivariable analysis identified factors associated with hospital mortality; higher BMI (OR 1.047, 95% CI 1.013–1.083), higher ratio of fresh frozen plasma (FFP) to pRBCs (OR 2.744, 95% CI 1.1–6.844), and higher baseline SOFA scores (OR 1.3, 95% CI 1.175–1.437).

Conclusion:
In a cohort of critically ill medical patients undergoing resuscitation for hemorrhage, higher BMI, increased ratio of FFP to pRBCs, and higher SOFA scores were associated with increased mortality. Further studies are needed to clarify resuscitation practices associated with outcomes in this population.
Informing Simulation Design: A Qualitative Phenomenological Study of the Experiences of Bereaved Parents and Actors
Authors: Vemuri Sidharth , O'Neill Jenny , Hynson Jenny , Gillam Lynn 
Published: January 2022

Introduction
Simulations, which represent reality, are effective in pediatric healthcare communication skills education and training. Parents are increasingly engaged in simulation development, particularly for authentic character development, to help achieve greater psychological fidelity. For simulated encounters related to a child's end-of-life, involvement of bereaved parents would make sense. However, this is challenging because there is limited research to guide their inclusion and significant responsibility for any approach to be thoughtful and psychologically safe for participating parents. This study explores the impact and experiences of bereaved parents and actors who participated in simulation design.

Methods
This qualitative phenomenological study involved five bereaved parents and two actors who participated in a full-day workshop to design and develop characters for use in a simulation. Individual semistructured interviews were conducted up to four weeks after the workshop. Data collected from these telephone interviews were analyzed using inductive content analysis.

Results
Bereaved parents found the workshop emotionally challenging but positive, worthwhile, and beneficial. Similarly, actors found the workshop helpful in character development and, although it was an intense experience for them, it validated the importance of their work. Key elements of our research findings could inform future such activities.

Conclusions
Involving bereaved parents in simulation design can be psychologically safe and beneficial for both parents and actors. Ongoing involvement of bereaved parents may lead to higher-quality simulated experiences, allowing clinicians to practice skills to enhance care provided at a child's end-of-life.
Hepatectomy Versus Sorafenib in Advanced Nonmetastatic Hepatocellular Carcinoma
Authors: Famularo Simone , Donadon Matteo , Cipriani Federica , Giuliante Felice , Ferri Silvia , Celsa Ciro , Ferrero Alessandro , Foschi Francesco Giuseppe , Baiocchi Gian Luca , Biasini Elisabetta , Campani Claudia , Valle Raffaele Dalla , Pelizzaro Filippo , Baroni Gianluca Svegliati , Raimondo Giovanni , Mega Andrea , Chiarelli Marco , Maestri Marcello , Gasbarrini Antonio , Jovine Elio , Grazi Gian Luca , Rapaccini Gian Ludovico , Ruzzenente Andrea , Morisco Filomena , Sacco Rodolfo , Memeo Riccardo , Crespi Michele , Antonucci Adelmo , Bernasconi Davide P. , Romano Fabrizio , Griseri Guido , Aldrighetti Luca , Torzilli Guido , Trevisani Franco ,   on behalf of ITA.LI.CA Group and HE.RC.O.LE.S. Group
Published: January 2022

Objective:
The aim of the study was to compare SURG vs SOR regarding the OS and progression-free survival (PFS) in a real-world clinical scenario.

Background data:
The treatment for advanced nonmetastatic HCC belonging to the Barcelona Clinic Liver Cancer stage C (BCLC C) is still controversial.

Methods:
BCLC C patients without extrahepatic spread and tumoral invasion of the main portal trunk were considered. Surgical patients were obtained from the HE.RC.O.LE.S. Register, whereas sorafenib patients were obtained from the ITA.LI.CA register The inverse probability weighting (IPW) method was adopted to balance the confounders between the 2 groups.

Results:
Between 2008 and 2019, 478 patients were enrolled: 303 in SURG and 175 in SOR group. Eastern Cooperative Oncological Group Performance Status (ECOG-PS), presence of cirrhosis, steatosis, Child-Pugh grade, hepatitis B virus and hepatitis C virus, alcohol intake, collateral veins, bilobar disease, localization of the tumor thrombus, number of nodules, alpha-fetoprotein, age, and Charlson Comorbidity index were weighted by IPW to create two balanced pseudo-populations: SURG = 374 and SOR = 263. After IPW, 1–3–5 years OS was 83.6%, 68.1%, 55.9% for SURG, and 42.3%, 17.8%, 12.8% for SOR (P < 0.001). Similar trends were observed after subgrouping patients by ECOG-PS = 0 and ECOG-PS >0, and by the intrahepatic location of portal vein invasion. At Cox regression, sorafenib treatment (hazard ratio 4.436; 95% confidence interval 3.19–6.15; P < 0.001) and Charlson Index (hazard ratio 1.162; 95% confidence interval 1.06–1.27; P = 0.010) were the only independent predictors of mortality. PFS at 1–3–5 years were 65.9%, 40.3%, 24.3% for SURG and 21.6%, 3.5%, 2.9% for SOR (P = 0.007).

Conclusions:
In BCLC C patients without extrahepatic spread but with intrahepatic portal invasion, liver resection, if feasible, was followed by better OS and PFS compared with sorafenib.
Donor-derived Cell-free DNA Complements De Novo Class II DSA in Detecting Late Alloimmune Injury Post Kidney Transplantation
Authors: Butiu Maria , Obrisca Bogdan , Sibulesky Lena , Bakthavatsalam Ramasamy , Smith Kelly D. , Gimferrer Idoia , Warner Paul , Ismail Gener , Leca Nicolae 
Published: January 2022

Background.
We sought to evaluate the association between de novo donor-specific antibodies (dnDSAs) class and their mean fluorescence intensity (MFI) with donor-derived cell-free DNA (dd-cfDNA), aiming to further clarify the biomarker utility of these noninvasive tests in relation to renal allograft function and histology.

Methods.
The study included kidney transplant recipients (n = 171) who underwent surveillance testing with DSA and dd-cfDNA as part of their clinical care between September 2017 and December 2019 at our center.

Results.
We identified dnDSA in 43 patients (25%) at a median of 4.63 y (IQR, 1.5–7) posttransplant. The presence of DSA with MFI >2500 was associated with a median dd-cfDNA of 0.96% (IQR, 0.26–2.95) significantly higher than in patients with DSA MFI <2500 (0.28%; IQR, 0.19–0.39) or without detectable DSA (0.22%; IQR, 0.17–0.37; P < 0.001). Class II dnDSAs were the most prevalent dnDSA (88.3%), the majority with MFI >2500 (82.9%). Patients with DQ-dnDSAs (47.4%) had higher MFI and dd-cfDNA levels than other class II dnDSAs. By comparison, all patients that developed only class I DSAs had MFI <2500 and a low dd-cfDNA. In addition, the serum creatinine was 1.55 ± 0.48 mg/dL in those dnDSA-negative, 1.15 ± 0.37 mg/dL in those with dnDSA MFI <2500, and 1.53 ± 0.66 mg/dL in those with dnDSA MFI >2500 (P = 0.05). After multivariate adjustment, an elevated dd-cfDNA was independently associated with the presence of dnDSA with MFI ≥2500. We identified that both dd-cfDNA and dnDSAs were strongly associated with antibody-mediated rejection, whereas for individual Banff histological lesions, DSA MFIs ≥2500 had the strongest association with C4d staining score and dd-cfDNA >1% with microvascular inflammation.

Conclusions.
Our study identifies class II dnDSA as being strongly associated with late alloimmune injury post kidney transplant independent of allograft dysfunction and shows that dd-cfDNA may complement the clinical significance of dnDSAs.
Algorithmic Fairness in Computational Medicine
Authors: Xu Jie , Xiao Yunyu , Wang Wendy Hui , Ning Yue , Shenkman Elizabeth A , Bian Jiang , Wang Fei 
Published: January 2022

ABSTRACTMachine learning models are increasingly adopted for facilitating clinical decision-making. However, recent research has shown that machine learning techniques may result in potential biases when making decisions for people in different subgroups, which can lead to detrimental effects on the health and well-being of vulnerable groups such as ethnic minorities. This problem, termed algorithmic bias, has been extensive studied in theoretical machine learning recently. However, how it will impact medicine and how to effectively mitigate it still remains unclear. This paper presents a comprehensive review of algorithmic fairness in the context of computational medicine, which aims at improving medicine with computational approaches. Specifically, we overview the different types of algorithmic bias, fairness quantification metrics, and bias mitigation methods, and summarize popular software libraries and tools for bias evaluation and mitigation, with the goal of providing reference and insights to researchers and practitioners in computational medicine.
The mycotoxin Beauvericin exhibits immunostimulatory effects on dendritic cells via activating the TLR4 signaling pathway
Authors: Yang Xiaoli , Ali Shafaqat , Zhao Manman , Richter Lisa , Schäfer Vanessa , Schliehe-Diecks Julian , Frank Marian , Qi Jing , Larsen Pia-Katharina , Skerra Jennifer , Islam Heba , Wachtmeister Thorsten , Alter Christina , Huang Anfei , Bhatia Sanil , Köhrer Karl , Kirschning Carsten , Weighardt Heike , Kalinke Ulrich , Kalscheuer Rainer , Uhrberg Markus , Scheu Stefanie 
Published: January 2022

AbstractBeauvericin (BEA), a mycotoxin of the enniatin family produced by various toxigenic fungi, has been attributed multiple biological activities such as anti-cancer, anti-inflammatory, and anti-microbial functions. However, effects of BEA on dendritic cells remain unknown so far. Here, we identified effects of BEA on murine granulocyte–macrophage colony-stimulating factor (GM-CSF)-cultured bone marrow derived dendritic cells (BMDCs) and the underlying molecular mechanisms. BEA potently activates BMDCs as signified by elevated IL-12 and CD86 expression. Multiplex immunoassays performed on myeloid differentiation primary response 88 (MyD88) and toll/interleukin-1 receptor (TIR) domain containing adaptor inducing interferon beta (TRIF) single or double deficient BMDCs indicate that BEA induces inflammatory cytokine and chemokine production in a MyD88/TRIF dependent manner. Furthermore, we found that BEA was not able to induce IL-12 or IFNβ production in Toll-like receptor 4 (Tlr4)-deficient BMDCs, whereas induction of these cytokines was not compromised in Tlr3/7/9 deficient BMDCs. This suggests that TLR4 might be the functional target of BEA on BMDCs. Consistently, in luciferase reporter assays BEA stimulation significantly promotes NF-κB activation in mTLR4/CD14/MD2 overexpressing but not control HEK-293 cells. RNA-sequencing analyses further confirmed that BEA induces transcriptional changes associated with the TLR4 signaling pathway. Together, these results identify TLR4 as a cellular BEA sensor and define BEA as a potent activator of BMDCs, implying that this compound can be exploited as a promising candidate structure for vaccine adjuvants or cancer immunotherapies.
SARS-CoV-2 antibody profile of naturally infected and vaccinated individuals detected using qualitative, semi-quantitative and multiplex immunoassays
Authors: Meyers Jamie , Windau Anne , Schmotzer Christine , Saade Elie , Noguez Jaime , Stempak Lisa , Zhang Xiaochun 
Published: January 2022

ABSTRACTAntibody profiling of vaccinated versus naturally infected individuals is important in evaluating immunity and aiding diagnosis and booster strategies. This study measured antibodies against different antigen targets in healthcare workers (HCW) who have been fully vaccinated with mRNA vaccines, recovered from natural infection, or patients during active infection. All vaccinated individuals were positive for anti-RBD, anti-S1, and anti-S2 antibodies. The median index and interquartile range (IQR) by the Atellica IgG assay were 179 and 140-291 respectively. Among the different antigen targets within the Bioplex assay, the levels of anti-RBD were highest (median >3200 U/mL; IQR >3200 to >3200 U/mL), followed by anti-S1 (median 2132 U/mL; IQR 1649->3200 U/mL) and anti-S2 (median=42 U/mL; IQR=24-76 U/mL). The non-vaccinated recovered cohort showed 90% seropositivity (median index >10; IQR 3.6->10) by Atellica total antibody, 73% by Atellica IgG (median index 3.3; IQR 0.9-9.4), 84% by Bioplex anti-RBD (median 62; IQR 12-269 U/mL), 77% by Bioplex anti-S1 (median 45; IQR 10-83 U/mL), 37% by Bioplex anti-S2 (median 7; IQR 1-12 U/mL), and 79% by Bioplex anti-nucleocapsid (median 69; IQR 20-185U/mL) respectively. The active infection cohort exhibited a similar pattern as the recovered cohort. About 88% and 78% of the recovered and active infection cohort produced both anti-spike and anti-N antibodies with Anti-S1/anti-N ratios ranging from 0.07-16.26. In summary, fully vaccinated individuals demonstrated an average of 50-fold higher antibody levels than naturally infected unvaccinated individuals with immune reactivity strongly towards RBD/S1 and a weak response to S2. The results support vaccination regardless of previous COVID-infection status.