bluuebunny/crossref_metadata_2025 huggingface dataset:
GDF15, Genetic Risk Factor for Hyperemesis Gravidarum, Inversely Associated With Pregnancy Weight Gain [ID: 1358449]
Authors: Fejzo Marlena , Zöllner Julia , Pujol-Gualdo Natàlia , Laisk Triin ,   Estonian Biobank Research Team, Finer Sarah , van Heel David ,   Genes & Health Research Team, Wang Xinran , Cortessis Victoria , Mendez Joel Sanchez , Murcia Vanessa , MacGibbon Kimber W. , Youssefzadeh Ariane , Sweeney Heather , Tavakoli Amin , Nguyen Michelle T. , Mancuso Nicholas , Mullin Patrick M.
Published: May 2023

INTRODUCTION:

Hyperemesis gravidarum (HG), a highly heritable condition, complicates ∼3% of pregnancies and is associated with adverse outcomes related to inadequate maternal weight gain. We report the largest-ever genome-wide association study (GWAS) of HG, composed of 8,960 cases and 369,843 controls. We identified associations with genes encoding GDF15 and its receptor GFRAL, so we compared changes in circulating GDF15 to weight gain in hospitalized HG patients.

METHODS:

We performed a meta-analysis of six independent studies: a multiancestry whole-exome sequencing study from the United States, four GWASs of European ancestry from 23andMe, Inc., research participants, FinnGen, Estonian and UK Biobanks, and a GWAS of British Bangladeshis and Pakistanis. We also studied three hospitalized HG patients, assessing serum GDF15 and weight at admission and discharge. Institutional review board approval was obtained.

RESULTS:

GDF15 was the greatest significant risk factor for HG in the meta-analysis (P= 2.47E-47) and each individual GWAS. Association with GFRAL (P=8.85E-09) further implicates the GDF15/GFRAL pathway in HG etiology. The solitary HG patient with lower GDF15 at discharge was the only one who gained weight during hospitalization.

CONCLUSION:

Overall, this study contributes to our understanding of the biology of HG and may inform future research evaluating new treatment avenues. Of note, drugs blocking GDF15/GFRAL mitigate appetite, weight loss, and vomiting in animal models. These drugs are currently in clinical trials of cancer cachexia, a disease with similar symptoms to HG. The strong link of HG to the GDF15/GFRAL pathway suggests that these drugs, if safe, hold great promise for improving symptoms and weight gain in HG patients.
Late Prenatal Care as a Risk Factor for Preeclampsia [ID: 1377685]
Authors: Hashmi Nabiha , Sung Sharon
Published: May 2023

INTRODUCTION:

Hypertensive disorders of pregnancy including preeclampsia account for 16% of maternal deaths in high-income countries. The American College of Obstetricians and Gynecologists lists a number of known risk factors for preeclampsia in its Practice Bulletin No. 222, “Gestational Hypertension and Preeclampsia.” The objective of this study was to identify whether late prenatal care, not a documented risk factor, is associated with an increased risk of preeclampsia.

METHODS:

A secondary analysis was performed on a dataset from an IRB-approved research study looking at chronic hypertension and contraception after pregnancy. As chronic hypertension is associated with preeclampsia and can be diagnosed in pregnancy by elevated blood pressures before 20 weeks of gestation, the dataset allowed comparison of patients who presented to care before 20 weeks versus after 20 weeks. Data were analyzed using descriptive statistics, chi-square, Student t test, and multivariate logistic regression.

RESULTS:

A total of 2,147 patients were included. 1,826 patients had early prenatal care (before 20 weeks) and 321 patients had late prenatal care (after 20 weeks). 8.5% of patients with early prenatal care had preeclampsia, compared to 12.1% of patients with late prenatal care (odds ratio 1.49, P=.0359, 95% CI 1.0266–2.1652). After multivariate logistic regression modeling, late prenatal care was a risk factor significantly associated with preeclampsia in African American patients (P=.030).

CONCLUSION:

Patients presenting for prenatal care in the second half of pregnancy are at increased risk of developing preeclampsia. Anticipatory guidance and education should be targeted for these patients.
Intravenous Iron Compared With Oral Iron Supplementation for the Treatment of Postpartum Anemia
Authors: Saad Antonio F. , Stepanek Rachel , Kothmann Makenzie , Wilson-Jimenez Maria , McCoy Leah , Aguillon Brenda , Salazar Ashley , Saade George R.
Published: May 2023

Postpartum anemia is a significant maternal comorbidity that affects 50% of patients in the United States. It has been associated with maternal impaired cognition, depression, and fatigue, ultimately affecting mother–child bonding and neonatal care. Oral iron supplementation is currently the first-line treatment for women with iron-deficiency anemia postpartum. The effectiveness of oral iron is diminished by variability in absorption, discomforting side effects, and poor compliance, limitations that can be overcome with intravenous (IV) iron. However, IV iron is costly and needs to be administered under supervision in a hospital or outpatient clinical setting. We performed a pragmatic, double-blinded, feasibility randomized controlled trial of daily oral compared with IV iron administered after delivery but before hospital discharge. We found that patients randomized to IV iron had higher hemoglobin levels after 6 weeks postpartum than those randomized to oral iron. Our trial shows that it is feasible to administer IV iron during the delivery admission and that larger multicenter clinical trials are warranted.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT05047211.
Third Generation Rotational Percutaneous Osteotomy to Hallux Valgus
Authors: Nunes Gustavo A. , Baumfeld Tiago
Published: May 2023

Hallux valgus (HV) is now recognized as a triplane deformity with pronation being a very important factor to be addressed. This article describes a modified third generation rotational percutaneous osteotomy for correction of HV. A guide is described and used in this technique to help surgeons correct pronation with accuracy and reproducibility. This technique allows, through a percutaneous approach, a triplane correction of the HV deformity.

Level of Evidence: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Randomized Controlled Trials in ICU in the Four Highest-Impact General Medicine Journals
Authors: Kampman Jasper M. , Sperna Weiland Nicolaas H. , Hermanides Jeroen , Hollmann Markus W. , Repping Sjoerd , Horn Janneke
Published: May 2023

OBJECTIVE:

To study ICU trials published in the four highest-impact general medicine journals by comparing them with concurrently published non-ICU trials in the same journals.

DATA SOURCES:

PubMed was searched for randomized controlled trials (RCTs) published between January 2014 and October 2021 in the New England Journal of Medicine, The Lancet, the Journal of the American Medical Association, and the British Medical Journal.

STUDY SELECTION:

Original RCT publications investigating any type of intervention in any patient population.

DATA EXTRACTION:

ICU RCTs were defined as RCTs exclusively including patients admitted to the ICU. Year and journal of publication, sample size, study design, funding source, study outcome, type of intervention, Fragility Index (FI), and Fragility Quotient were collected.

DATA SYNTHESIS:

A total of 2,770 publications were screened. Of 2,431 original RCTs, 132 (5.4%) were ICU RCTs, gradually rising from 4% in 2014 to 7.5% in 2021. ICU RCTs and non-ICU RCTs included a comparable number of patients (634 vs 584, p = 0.528). Notable differences for ICU RCTs were the low occurrence of commercial funding (5% vs 36%, p < 0.001), the low number of RCTs that reached statistical significance (29% vs 65%, p < 0.001), and the low FI when they did reach significance (3 vs 12, p = 0.008).

CONCLUSIONS:

In the last 8 years, RCTs in ICU medicine made up a meaningful, and growing, portion of RCTs published in high-impact general medicine journals. In comparison with concurrently published RCTs in non-ICU disciplines, statistical significance was rare and often hinged on the outcome events of just a few patients. Increased attention should be paid to realistic expectations of treatment effects when designing ICU RCTs to detect differences in treatment effects that are reliable and clinically relevant.
Vitamin D insufficiency and serum levels related to the incidence and stage of cutaneous melanoma: a systematic review and meta-analysis
Authors: Shellenberger Richard A. , Gowda Sunaina , Kurn Heidi , Albright Jeremy , Mayo MacKenzie H.
Published: May 2023

Cutaneous melanoma (CM) is the deadliest skin cancer, and vitamin D insufficiency has been suggested as a risk factor. We evaluated the relationship between both vitamin D insufficiency and 25-hydroxy vitamin D levels with the incidence and stage of CM. Five databases were searched from inception until 11 July 2022. Inclusion criteria were cohort and case-control studies that reported mean 25-hydroxy vitamin D levels or the presence of vitamin D insufficiency in CM patients and compared with healthy controls; or those that reported vitamin D insufficiency and Breslow tumor depth or the development of metastasis in CM. Fourteen studies were included in the analysis. Statistically significant relationships were found between vitamin D level <20 ng/dl and incidence of CM [pooled RR 1.45, 95% confidence interval (CI) 1.04–2.02]; lower mean vitamin D level and Breslow depth >1 mm (SMD 0.19, 95% CI 0.11–0.28); and vitamin D level >20 ng/dl and Breslow depth <1 mm (pooled RR 0.69, 95% CI 0.58–0.82). Statistical significance was not found in the relationships between vitamin D levels and the presence of metastasis (pooled SMD −0.13, 95% CI, −0.38 to 0.12); or mean vitamin D level and the incidence of CM (pooled SMD −0.39, 95% CI, −0.80 to 0.01). We identified an association of increased incidence of CM and vitamin D insufficiency, as well as less favorable Breslow tumor depth with lower levels of vitamin D and the presence of vitamin D insufficiency.
Nodular type predominance of head and neck cutaneous malignant melanoma in Asian populations leads to poor outcome and low survival
Authors: Yoo Hyokyung , Park Sunkyu , Kim Sang Wha
Published: May 2023

Cutaneous malignant melanomas of the head and neck (HNM) are proposed to have notable histological and clinical differences from those at other sites (other melanoma); however, HNMs among Asians have remained poorly understood. This study aimed to investigate the clinicopathological features and prognostic factors of HNM in Asians. Asian melanoma patients who underwent surgical treatment from January 2003 to December 2020 were retrospectively reviewed. The clinicopathological features and risk factors for local recurrence, lymph node metastasis, and distant metastasis were analyzed. Among 230 patients, 28 (12.2%) were diagnosed with HNM, and 202 (87.8%) with other melanoma. The histologic subtype significantly differed as the nodular type was predominant in HNM whereas the acral lentiginous type was predominant in other melanoma (P < 0.001). HNM was significantly associated with higher local recurrence (P = 0.045), lymph node metastasis (P = 0.048), distant metastasis (P = 0.023), and lower 5-year disease-free survival (P = 0.022) than other melanoma. Ulceration was the risk factor for lymph node metastasis based on multivariable analysis (P = 0.013). A high proportion of HNM present as the nodular subtype in Asians, leading to poor outcomes and low survival. Therefore, more cautious surveillance, evaluation, and aggressive treatment are required.
Fostering Improved Mental and Spiritual Health of Nursing Students During COVID and Beyond
Authors: McKinnon Kathy , Hubley Alex
Published: May 2023

Nursing school is a highly stressful experience for most nursing students. The COVID-19 pandemic intensified stress levels for undergraduate students with serious impacts on mental health. Faculty acted to provide solutions such as debriefings and fostering safe places inside and outside of class where students could release negative emotions and develop positive coping skills. The integration of faith and the caring outreach by the faculty also strengthened students' emotional, mental, and spiritual health.
Search for key genes, key signaling pathways, and immune cell infiltration in uterine fibroids by bioinformatics analysis
Authors: Li Feng , Wang Junqing , Liu Wenqiong
Published: May 2023

Uterine fibroids grow in the myometrium and are benign tumors. The etiology and molecular mechanism are not fully understood. Here, we hope to study the potential pathogenesis of uterine fibroids by bioinformatics. Our aim is to search for the key genes, signaling pathways and immune infiltration about the development of uterine fibroids. The GSE593 expression profile was downloaded from the Gene Expression Omnibus database, which contains 10 samples, including 5 uterine fibroids samples and 5 normal controls. Bioinformatics methods were used to find differentially expressed genes (DEGs) in tissues and further analyze the DEGs. R (version 4.2.1) software was used for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analysis of DEGs in uterine leiomyoma tissues and normal control. STRING database was used to generate protein-protein interaction (PPI) networks of key genes. Then, CIBERSORT was used to assess the infiltration of immune cells in uterine fibroids. A total of 834 DEGs were identified, of which 465 were up-regulated and 369 were down-regulated. GO andKEGG pathway analysis showed that the DEGs were mainly concentrated in extracellular matrix and cytokine related signaling pathways. We identified 30 key genes in DEGs from the PPI network. There were some differences in infiltration immunity between the 2 tissues. This study indicated that screening key genes, signaling pathways and immune infiltration by comprehensive bioinformatics analysis is helpful to understand the molecular mechanism of uterine fibroids and provide new insights into understanding the molecular mechanism.
Hollow screw fixation of type II avulsion fractures of the calcaneal tuberosity using the finite element analysis
Authors: Wang Chengwei
Published: May 2023

We aimed to establish a model of type II avulsion fractures of the calcaneal tuberosity treated with 2 hollow screws implanted in different directions and to analyze the biomechanical properties of the model using the finite element method. The Dicom data of the calcaneal bone obtained after computed tomography scan were inputted into Mimics 21.0 software and Geomagic Studio software to generate a 3D finite element digital model of the calcaneal bone. The model was then imported into SOLIDWORKS 2020 software. Based on the Beavis theory, the calcaneal bone was cut to build a type II avulsion fracture model of the calcaneal tuberosity; the calcaneal fracture was then simulated by internal fixation using hollow screws. Two screws were used to fix the calcaneal bone from the calcaneal tuberosity in different ways, resulting in 3 different calcaneal models (Model 1 involved 2 screws for fixing the fracture vertically; Model 2 had 2 screws for fixing the fracture cross-wise; and Model 3 had 2 screws for fixing the fracture parallelly). Three internal fixation models were loaded under the same conditions, and lines finite element analysis was then performed to calculate the stress distribution of the generated internal fixation models. Under the same loading conditions, compared with Models 2 and 3, Model 1 exhibited smaller maximum displacement values of the heel bone, maximum equivalent force values of the screws, and more dispersed stresses. Avulsion fractures of the calcaneal tuberosity can be treated using 2 screws to fix the fracture vertically (Model 1), which is more biomechanically relevant.
Gastroenterologist focus of clinical practice affects adenoma detection in screening colonoscopy
Authors: Razjouyan Hadie , Kim Myunghoon , Levenick John , Clarke Kofi , McGarrity Thomas
Published: May 2023

Our objective was to determine whether the clinical focus of gastroenterology practice would affect screening colonoscopy quality metrics, specifically adenoma detection (AD). In a retrospective study of screening colonoscopies, gastroenterologists were categorized based on their clinical subspecialty focus into general/motility, hepatology, inflammatory bowel disease (IBD), and interventional endoscopy. The primary outcome was AD with a secondary outcome of adenoma and/or sessile serrated polyp (SSP) detection (AD + SSP). A total of 5271 (male: 49.1%) complete colonoscopies were performed between 2010 and 2020 by 16 gastroenterologists (male: 62.5%, general/motility specialists: 3, hepatologists: 3, IBD specialists: 4, interventional endoscopists: 6). The AD and AD + SSP rate between each specialty focus were 27.5% and 31.0% for general/motility, 31.4% and 35.5% for hepatology, 38.4% and 43.6% for IBD, and 37.5% and 43.2% for interventional endoscopy. In regression analysis, patient’s male gender (odds ratios [OR]: 1.81, 95% CI: 1.60–2.05, P < .001), longer withdrawal time (OR: 1.16, 95% CI: 1.14–1.18, P < .001), hepatologist (OR: 1.25, 95% CI: 1.02–1.53, P = .029), IBD subspecialist (OR: 1.60, 95% CI: 1.30–1.98, P < .001), and interventional endoscopist (OR: 1.36, 95% CI: 1.13–1.64, P < .001) were independently associated with AD. Moreover, patient’s male gender (OR: 1.64, 95% CI: 1.45–1.85, P < .001), acceptable bowel preparation (OR: 1.29, 95% CI: 1.06–1.56, P = .010), withdrawal time (1.20, 95% CI: 1.18–1.22, P < .001), hepatologist (OR: 1.30, 95% CI: 1.07–1.59, P = .008), IBD subspecialist (OR: 1.72, 95% CI: 1.39–2.12, P < .001), interventional endoscopist (OR: 1.44, 95% CI: 1.20–1.72, P < .001) were independent factors that improved detection of AD + SSP. Subspecialty focus of practice was an important factor in AD rate along with the male gender of the patient, bowel preparation, and withdrawal time.
The efficacy and safety of intravenous administration of tranexamic acid in patients undergoing cardiac surgery: Evidence from a single cardiovascular center
Authors: Lin Pei-Shuang , Yao Yun-Tai , Tian Li-Juan , Jiang Juan-Juan , Zhang Yang , He Li-Xian , Yu Yi-Ping , Ma Jie ,   The Evidence in Cardiovascular Anesthesia (EICA) Group
Published: May 2023

Background:

The current study was performed to systemically review the efficacy and safety of tranexamic acid (TXA) in patients undergoing cardiac surgery at a single large-volume cardiovascular center.

Methods:

A computerized search of electronic databases was performed to identify all relevant studies using search terms till December 31st, 2021. The primary outcomes were postoperative blood loss and the composite incidence of mortality and morbidities during hospitalization. Secondary outcomes included postoperative massive bleeding and transfusion, postoperative recovery profiles, coagulation functions, inflammatory variables, and biomarkers of vital organ injury.

Results:

Database search yielded 23 qualified studies including 27,729 patients in total. Among them, 14,136 were allocated into TXA group and 13,593 into Control group. The current study indicated that intravenous TXA significantly reduced total volume of postoperative bleeding in both adult and pediatric patients, and that medium- and high-dose TXA were more effective than low-dose TXA in adult patients (P < .05). The current study also demonstrated that intravenous TXA, as compared to Control, remarkably reduced postoperative transfusion incidences and volume of red blood cell and fresh frozen plasma, and reduced postoperative transfusion incidence of platelet concentrates (PC) (P < .05) without obvious dose-effects (P > .05), but TXA did not reduce PC transfusion volume postoperatively in adult patients (P > .05). For pediatrics, TXA did not significantly reduce postoperative transfusion incidence and volume of allogenic red blood cell, fresh frozen plasma and PC (P > .05). Additionally, the current study demonstrated that intravenous TXA did not influence the composite incidence of postoperative mortality and morbidities in either adults or pediatrics during hospitalization (P > .05), and that there was no obvious dose-effect of TXA in adult patients (P > .05).

Conclusions:

This current study suggested that intravenous TXA significantly reduced total volume of postoperative bleeding in both adult and pediatric patients undergoing cardiac surgery at the single cardiovascular center without increasing the composite incidence of mortality and morbidities.
A nomogram for predicting osteoarthritis based on serum biomarkers of bone turnover in middle age: A cross-sectional study of PTH and β-CTx
Authors: Chen Xueqiang , Xu Juntao , Zhang Houjian , Yu Lixin
Published: May 2023

The objective of this study was to investigate the diagnostic model of osteoarthritis by bone turnover markers in Chinese middle-aged subjects. The study was designed as a cross-sectional investigation with 305 participants aged 45 to 64. Radiographs of tibiofemoral knee joints were used for diagnose osteoarthritis. Radiographic grading, evaluated using the Kellgren and Lawrence grading scale (K-L), was scored by 2 experienced observers who were blinded to the source of subjects. An optimal model was developed by logistic regression. And the prognostic performance of the selected model was assessed by the area under the receiver operating characteristic curve. The prevalence of osteoarthritis was 52.29% (n = 137/262) in middle age. β-CTx levels tended to increase according to the K-L grades, whereas PTH levels significantly decrease. levels of 25(OH)D, β-CTx, and PTH were each significantly associated with osteoarthritis risk (P < .05). Based on the estimated parameters of the optimal model, a nomogram was constructed for predicting osteoarthritis. These data suggest that the combination of PTH and β-CTx could significantly improve the prognosis of osteoarthritis in middle age, and that the nomogram can assist primary physicians in the identification of high-risk men.
The relationship between stress and sleep quality: The mediating effect of fatigue and dizziness among patients with cardiovascular disease
Authors: Park Hwan-Cheol , Oh Jihyun
Published: May 2023

Cardiovascular disease is the leading cause of non-noncommunicable disease mortality worldwide. Therefore, this study analyzes the mediating effect of dizziness and fatigue in the relationship between stress and sleep quality in patients with heart disease. This study was conducted on patients with heart disease diagnosed by a cardiologist from December 7, 2021 to August 30, 2022 at the Outpatient Department of Cardiology at Hanyang University Hospital in Guri-si, Gyeonggi-do. To verify the serial multiple mediation effect, serial multiple mediation analysis was performed using SPSS Macro Process Model 6 as the most appropriate verification method for this study. The analysis indicated that the more dizziness a participant experienced, the more severe their physical and psychological fatigue and the poorer their quality of sleep. Also, the more severe the physical fatigue, the worse the psychological fatigue and the worse the quality of sleep. In other words, the more severe the psychological fatigue, the poorer the quality of sleep. In summary, in the relationship in which stress in patients with heart disease affects sleep quality, stress is a variable that directly affects sleep quality, and this means that the stress of patients with heart disease can affect the quality of sleep through the parameters, dizziness and fatigue, sequentially; this research model can thus be considered a partial mediator model. Fatigue in patients with cardiovascular disease had a direct effect on sleep quality, and there was a mediating effect through dizziness and fatigue in the relationship between stress and sleep quality. Therefore, it is necessary to develop a sleep management program that can improve the quality of sleep in patients with cardiovascular disease as well as a nursing intervention plan that can alleviate fatigue and control stress in such patients.
Pediatric primary renal lymphoma presenting with multiple masses: A challenging case report and narrative review
Authors: He Xiao , Di Min , Wang Guan-Nan , Gao Jian-Bo
Published: May 2023

Rationale:

Only 20 cases of pediatric primary renal non-Hodgkin’s lymphoma have been reported since 1995, rare cases and a variety of imaging manifestations have led to difficulties in its diagnosis and treatment.

Patient concerns:

Herein, we share in detail a case of primary renal lymphoma (PRL) in a child and summarize the common clinical manifestations, imaging features, and prognostic factors of pediatric PRL by retrospectively analyzing cases reported in the literature. A 2-year-old boy presented to the clinic with a large mass on the right side of his abdomen along with loss of appetite.

Diagnoses:

Imaging revealed a large right renal mass, nearly replacing the entire renal tissue, along with numerous small nodules in the left kidney. Given no local adenopathy and metastases, the diagnosis was unclear. A percutaneous renal puncture was performed, which proved the diagnosis of Burkitt’s lymphoma. Since no bone marrow involvement, this child was diagnosed with pediatric PRL.

Interventions:

This PRL boy was treated with the NHL-BFM95 protocol and supportive care.

Outcomes:

Unfortunately, this boy died of multiple organ failure in the fifth month of treatment.

Lessons:

As per literature review, the presentation of pediatric PRL is fatigue, loss of appetite, weight loss, abdominal swelling, or other nonspecific symptoms. Although in 81% of cases it often infiltrates the bilateral kidneys, urine abnormalities caused by pediatric PRL are uncommon. 76.2% of pediatric PRL were boys and 2/3 of all cases presented as diffuse renal enlargement. Those PRL presented as masses could easily be misdiagnosed as WT or other malignancies. Absent of local enlarged lymph node, no necrosis or calcification suggest atypical presentation of renal masses and a percutaneous biopsy is needed in timely establishing the accurate diagnosis for appropriate treatment. Based on our experience, percutaneous renal puncture core biopsy is a safe procedure.
Prognosis prediction for impaired consciousness recovery in stroke patients using videofluoroscopic swallowing study: A retrospective observational study
Authors: Jang Sung Ho , Kwak Soyoung , Lee Min Young
Published: May 2023

Prognosis prediction of impaired consciousness is clinically important for establishing therapeutic strategies, determining a rehabilitative goal and functional outcome, and estimating rehabilitative therapy duration. In this study, we investigated the prognosis prediction value of videofluoroscopic swallowing study (VFSS) in recovery of impaired consciousness in stroke patients. Fifty-one patients with impaired consciousness who underwent VFSS during the early stage of stroke between 2017 and 2021 were recruited in this retrospective study. VFSS were performed using modified Logemann protocol, and bonorex was used as the liquid contrast medium. The penetration-aspiration scale (PAS) was graded for all patients, and they were classified into 2 groups depending on the presence of aspiration on liquid material: the aspiration-positive group with a PAS score ≥ 6, and the aspiration-negative group with a PAS score < 6. The coma recovery scale-revised (CRS-R) was used to evaluate patients’ conscious state at the time of VFSS and 3 months after. Statistical analysis was performed using independent t test and Pearson’s correlation. The increase in total CRS-R score from time of VFSS to 3 months later was greater in aspiration-negative group than in aspiration-positive group (P < .05). A moderate negative correlation was observed between liquid PAS score and the increase in total CRS-R score (r = −0.499, P < .05). Among 6 CRS-R subscales, a strong negative correlation was observed between liquid PAS score and the communication score increase (r = −0.563, P < .05), while moderate negative correlations were detected between liquid PAS score and the increases in auditory (r = −0.465, P < .05), motor (r = −0.372, P < .05), oromotor (r = −0.426, P < .05), and arousal (r = −0.368, P < .05) scores. We observed that patients without aspiration on videofluoroscopic swallowing study showed better recovery of impaired consciousness, and the degree of penetration and aspiration had a predictive value for impaired consciousness prognosis in the early stage of stroke.
Acute Mania in a Patient With Primary Adrenal Insufficiency Due to Autoimmune Adrenalitis: A Case Report
Authors: Brown Nolan J. , Wang Alex , Fote Gianna , Gabriel Chris , Farokhpay Reza , Luo John
Published: May 2023

We describe a rare case of acute mania in the setting of autoimmune adrenalitis. A 41-year-old male with no previous psychiatric diagnoses presented with impulsivity, grandiosity, delusions of telepathy, and hyperreligiosity following a previous hospitalization for an acute adrenal crisis and 2 subsequent days of low-dose corticosteroid treatment. Workups for encephalopathy and lupus cerebritis were negative, raising concern that this presentation might represent steroid-induced psychosis. However, discontinuation of corticosteroids for 5 days did not resolve the patient’s manic episode, suggesting that his clinical presentation was more likely new onset of a primary mood disorder or a psychiatric manifestation of adrenal insufficiency itself. The decision was made to restart corticosteroid treatment for the patient’s primary adrenal insufficiency (formerly known as Addison disease), coupled with administration of both risperidone and valproate for mania and psychosis. Over the following 2 weeks, the patient’s manic symptoms resolved, and he was discharged home. His final diagnosis was acute mania secondary to autoimmune adrenalitis. Although acute mania in adrenal insufficiency is quite rare, clinicians should be aware of the range of psychiatric manifestations associated with Addison disease so that they can pursue the optimal course of both medical and psychiatric treatment for these patients.
“Targeted Muscle Reinnervation at the Time of Amputation Decreases Recurrent Symptomatic Neuroma Formation”
Authors: Goodyear Evelyn G. , O’Brien Andrew L. , West Julie M. , Huayllani Maria T. , Huffman Allison C. , Souza Jason M. , Schulz Steven A. , Moore Amy M.
Published: May 2023

Background:

Targeted Muscle Reinnervation (TMR) is an effective technique for the prevention and management of phantom limb pain (PLP) and residual limb pain (RLP) among amputees. The purpose of this study was to evaluate symptomatic neuroma recurrence and neuropathic pain outcomes between cohorts receiving TMR at the time of amputation (i.e., acute) versus TMR following symptomatic neuroma formation (i.e., delayed).

Methods:

A cross-sectional, retrospective chart review was conducted using patients receiving TMR between 2015 and 2020. Symptomatic neuroma recurrence and surgical complications were collected. A subanalysis was conducted for patients that completed Patient-Reported Outcome Measurement Information System (PROMIS) pain intensity, interference, and behavior as well as an 11-point numeric rating scale (NRS) forms.

Results:

105 limbs from 103 patients were identified with 73 acute TMR limbs and 32 delayed TMR limbs. 19% of the delayed TMR group had symptomatic neuromas recur in the distribution of original TMR compared to 1% of the acute TMR group (p<0.05). 85% the acute TMR group and 69% patients of the delayed TMR group completed pain surveys at final follow-up. Of this subanalysis, acute TMR patients reported significantly lower PLP PROMIS pain interference (p<0.05), RLP PROMIS pain intensity (p<0.05) and RLP PROMIS pain interference (p<0.05) in comparison to the delayed group.

Conclusions

Patients who underwent acute TMR reported improved pain scores and decreased rate of neuroma formation compared to TMR performed in a delayed fashion. These results highlight the promising role of TMR in the prevention of neuropathic pain and neuroma formation at time of amputation.

Level of Evidence:

Therapeutic, III
Six-month immune responses to mRNA-1273 vaccine in combination antiretroviral therapy treated late presenter people with HIV according to previous SARS-CoV-2 infection
Authors: Augello Matteo , Bono Valeria , Rovito Roberta , Tincati Camilla , d’Arminio Monforte Antonella , Marchetti Giulia
Published: May 2023

Objective:

Immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in people with HIV (PWH) with a history of late presentation (LP) and their durability have not been fully characterized.

Design:

In this prospective, longitudinal study, we sought to assess T-cell and humoral responses to SARS-CoV-2 mRNA vaccination up to 6 months in LP-PWH on effective combination antiretroviral therapy (cART) as compared to HIV-negative healthcare workers (HCWs), and to evaluate whether previous SARS-CoV-2 infection modulates immune responses to vaccine.

Methods:

SARS-CoV-2 spike (S)-specific T-cell responses were determined by two complementary flow cytometry methodologies, namely activation-induced marker (AIM) assay and intracellular cytokine staining (ICS), whereas humoral responses were measured by ELISA [anti-receptor binding domain (RBD) antibodies) and receptor-binding inhibition assay (spike-ACE2 binding inhibition activity), before vaccination (T0), 1 month (T1) and 5 months (T2) after the second dose.

Results:

LP-PWH showed at T1 and T2 significant increase of: S-specific memory and circulating T follicular helper (cTfh) CD4+T cells; polyfunctional Th1-cytokine (IFN-γ, TNF-α, IL-2)- and Th2-cytokine (IL-4)-producing S-specific CD4+T cells; anti-RBD antibodies and spike-ACE2 binding inhibition activity. Immune responses to vaccine in LP-PWH were not inferior to HCWs overall, yet S-specific CD8+T cells and spike-ACE2 binding inhibition activity correlated negatively with markers of immune recovery on cART. Interestingly, natural SARS-CoV-2 infection, while able to sustain S-specific antibody response, seems less efficacious in inducing a T-cell memory and in boosting immune responses to vaccine, possibly reflecting an enduring partial immunodeficiency.

Conclusions:

Altogether, these findings support the need for additional vaccine doses in PWH with a history of advanced immune depression and poor immune recovery on effective cART.
Predictors of Long-Term Visual Acuity in a Modern Cohort of Patients With Acute Idiopathic and Multiple Sclerosis–Associated Optic Neuritis
Authors: Jarocki Adrienne , Benard-Seguin Etienne , Gonzalez Lizbeth A. , Costello Fiona , Andrews Chris A. , Kerber Kevin , De Lott Lindsey B.
Published: May 2023

Background:

For patients with idiopathic or multiple sclerosis (MS)–associated optic neuritis (ON), the largest multicenter clinical trial (Optic Neuritis Treatment Trial [ONTT]) showed excellent visual outcomes and baseline high-contrast visual acuity (HCVA) was the only predictor of HCVA at 1 year. We aimed to evaluate predictors of long-term HCVA in a modern, real-world population of patients with ON and compare with previously published ONTT models.

Methods:

We performed a retrospective, longitudinal, observational study at the University of Michigan and the University of Calgary evaluating 135 episodes of idiopathic or MS-associated ON in 118 patients diagnosed by a neuro-ophthalmologist within 30 days of onset (January 2011–June 2021). Primary outcome measured was HCVA (Snellen equivalents) at 6–18 months. Multiple linear regression models of 107 episodes from 93 patients assessed the association between HCVA at 6–18 months and age, sex, race, pain, optic disc swelling, symptoms (days), viral illness prodrome, MS status, high-dose glucocorticoid treatment, and baseline HCVA.

Results:

Of the 135 acute episodes (109 Michigan and 26 Calgary), median age at presentation was 39 years (interquartile range [IQR], 31–49 years), 91 (67.4%) were women, 112 (83.0%) were non-Hispanic Caucasians, 101 (75.9%) had pain, 33 (24.4%) had disc edema, 8 (5.9%) had a viral prodrome, 66 (48.9%) had MS, and 62 (46.6%) were treated with glucocorticoids. The median (IQR) time between symptom onset and diagnosis was 6 days (range, 4–11 days). The median (IQR) HCVA at baseline and at 6–18 months were 20/50 (20/22, 20/200) and 20/20 (20/20, 20/27), respectively; 62 (45.9%) had better than 20/40 at baseline and 117 (86.7%) had better than 20/40 at 6–18 months. In linear regression models (n = 107 episodes in 93 patients with baseline HCVA better than CF), only baseline HCVA (β = 0.076; P = 0.027) was associated with long-term HCVA. Regression coefficients were similar and within the 95% confidence interval of coefficients from published ONTT models.

Conclusions:

In a modern cohort of patients with idiopathic or MS-associated ON with baseline HCVA better than CF, long-term outcomes were good, and the only predictor was baseline HCVA. These findings were similar to prior analyses of ONTT data, and as a result, these are validated for use in conveying prognostic information about long-term HCVA outcomes.
Fast and cost-effective SARS-CoV-2 variant detection using Oxford Nanopore full-length spike gene sequencing
Authors: Salazar Cecilia , Ferrés Ignacio , Paz Mercedes , Costábile Alicia , Moratorio Gonzalo , Moreno Pilar , Iraola Gregorio
Published: May 2023

Most biologically relevant and diagnostic mutations in the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genome have been identified in the S gene through global genomic surveillance efforts. However, large-scale whole-genome sequencing (WGS) is still challenging in developing countries due to higher costs, reagent delays and limited infrastructure. Consequently, only a small fraction of SARS-CoV-2 samples are characterized through WGS in these regions. Here, we present a complete workflow consisting of a fast library preparation protocol based on tiled amplification of the S gene, followed by a PCR barcoding step and sequencing using Nanopore platforms. This protocol facilitates fast and cost-effective identification of main variants of concern and mutational surveillance of the S gene. By applying this protocol, report time and overall costs for SARS-CoV-2 variant detection could be reduced, contributing to improved genomic surveillance programmes, particularly in low-income regions.
Quality characteristics of different parts of garlic sprouts produced by smart farms during growth
Authors: Choi Yu-Ri , Kim Su-Hwan , Lee Chae-Mi , Lee Dong-Hun , Lee Chae-Yun , Jo Hyeong-Woo , Jeong Jae-Hee , Oh Imkyung , Ha Ho-Kyung , Kim Jungsil , Huh Chang-Ki
Published: May 2023

Garlic sprouts can provide data on functional and food processing materials. This study compared the leaves, bulbs, and roots of garlic sprouts grown on smart farms during two growth periods (20 and 25 days). In addition, data for garlic bulbs grown in open fields were presented as reference materials. All garlic sprouts’ total free sugar content decreased as the growth period increased. All plant parts’ total organic acid content decreased as the growth period progressed, except for the root section. Potassium, phosphorus, and sulfur content increased during growth in all parts of the garlic sprouts. Alliin content decreased in all parts of the plant over time, whereas thiosulfinate content increased in the roots but decreased in the leaves and bulbs. Total polyphenol content increased in all parts of the plant during the growth period, except for the bulb, whereas the flavonoid content did not change significantly over time. The 2,2-diphenyl-1-picrylhydrazy (DPPH) and 2,2′-azinobis (3-ethylben-zothiazoline 6-sulfonate) (ABTS) free radical scavenging activities, as well as the superoxide dismutase (SOD)-like activity of garlic sprouts were 37.45-65.47%, 59.12-89.81%, and 89.52-98.59%, respectively. These activities tend to decrease during the growth period. Here, we showed that garlic sprouts have higher levels of functional substances and physiological activities than general garlic sprouts. It was also determined that a growth period of 20 days was suitable for garlic sprouts. Data for research on functional and food-processing materials can be obtained by analyzing garlic sprouts produced by smart farms.
MASIv2 enables standardization and integration of multi-modal single-cell and spatial omics data with one general framework
Authors: Xu Yang , Hayat Sikander
Published: May 2023

Data annotation and integration are two common tasks in large-scale and collaborative single-cell research. Rapid technological advancements have made diverse single-cell and spatial data modalities available. This data deluge brought up great challenges in data annotation and integration. Though different biological modalities preserve shared features to define the same cellular system, they often present unique angles to unravel a multi-level understanding about this system. Here, we present one general framework that uses modality-shared and -specific features for annotation and integration of single-cell and spatial omics data. We benchmark our framework with existing methods across different datasets and demonstrate its application in two real world tasks.
A Real-Time Deep Learning Approach for Inferring Intracranial Pressure from Routinely Measured Extracranial Waveforms in the Intensive Care Unit
Authors: Nair Shiker S. , Guo Alina , Boen Joseph , Aggarwal Ataes , Chahal Ojas , Tandon Arushi , Patel Meer , Sankararaman Sreenidhi , Azad Tej , Pirracchio Romain , Stevens Robert D.
Published: May 2023

Objective

Intracranial pressure (ICP) is a physiological variable used to assess the neurological state of patients with life-threatening intracranial pathology, such as traumatic brain injury or stroke. The current standard of care for measuring ICP requires a catheter to be inserted into the brain, which is associated with an appreciable risk of hemorrhage and infection. We hypothesize that ICP can be computed from extracranial waveforms routinely measured in the Intensive Care Unit (ICU), such as invasive arterial blood pressure (ABP), photoplethysmography (PPG), and electrocardiography (ECG).

Methods

We extracted 600 hours of simultaneous ABP, ECG, PPG, and ICP data (sampled at 125 Hz) across 10 different patients from the MIMIC III Waveform Database. These recordings were segmented into 10 second windows and used to train six different deep learning models with ABP, ECG, and PPG waveforms as input features. Models were evaluated in both a singlepatient analysis and multi-patient analysis.

Results

The performances of the six deep learning models were compared, revealing two tiers of performance. Among the top-tier models, the mean average error (MAE) for inferring ICP was approximately 1.50 mmHg for singlepatient analysis and 5 mmHg for multi-patient analysis.

Conclusions

These preliminary and novel results indicate the feasibility and accuracy of noninvasive ICP estimation by training deep learning models with extracranial physiological data. With further validation, this approach could be implemented in a continuous real-time fashion, thereby reducing risks associated with invasive monitoring and allowing more timely treatment of patients with critical brain injuries.
Adipocytes regulate fibroblast function, and their loss contributes to fibroblast dysfunction in inflammatory diseases
Authors: Faust Heather J. , Cheng Tan-Yun , Korsunsky Ilya , Watts Gerald F.M. , Gal-Oz Shani T. , Trim William , Kongthong Kurt , Jonsson Anna Helena , Simmons Daimon P. , Zhang Fan , Padera Robert , Chubinskaya Susan ,   Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network, Wei Kevin , Raychaudhuri Soumya , Lynch Lydia , Moody D. Branch , Brenner Michael B.
Published: May 2023

Fibroblasts play critical roles in tissue homeostasis, but in pathologic states can drive fibrosis, inflammation, and tissue destruction. In the joint synovium, fibroblasts provide homeostatic maintenance and lubrication. Little is known about what regulates the homeostatic functions of fibroblasts in healthy conditions. We performed RNA sequencing of healthy human synovial tissue and identified a fibroblast gene expression program characterized by enhanced fatty acid metabolism and lipid transport. We found that fat-conditioned media reproduces key aspects of the lipid-related gene signature in cultured fibroblasts. Fractionation and mass spectrometry identified cortisol in driving the healthy fibroblast phenotype, confirmed using glucocorticoid receptor gene (NR3C1) deleted cells. Depletion of synovial adipocytes in mice resulted in loss of the healthy fibroblast phenotype and revealed adipocytes as a major contributor to active cortisol generation viaHsd11β1expression. Cortisol signaling in fibroblasts mitigated matrix remodeling induced by TNFα- and TGFβ, while stimulation with these cytokines repressed cortisol signaling and adipogenesis. Together, these findings demonstrate the importance of adipocytes and cortisol signaling in driving the healthy synovial fibroblast state that is lost in disease.
Host-parasite interactions in perpetual darkness: macroparasite diversity in the cavefishAstyanax mexicanus
Authors: Santacruz Ana , Hernández-Mena David , Miranda-Gamboa Ramses , De León Gerardo Pérez-Ponce , Ornelas-García Claudia Patricia
Published: May 2023

Astyanax mexicanushas repeatedly colonized cave environments, displaying evolutionary parallelisms in many troglobitic traits. Despite being a model system for the study of adaptation to life in perpetual darkness, parasites infecting cavefish are practically unknown. In this study, we investigated the macroparasite communities of 18 cavefish populations from independent lineages and compared them with the parasite diversity of their sister surface fish populations, with the aim of better understanding the role that parasites play in the colonization of new environments. Thirteen parasite taxa were found in cavefish populations, including a subset of 10 of the 27 parasite taxa known for the surface populations. Parasites infecting the cavefish belong to five taxonomic groups: trematodes, monogeneans, nematodes, copepods, and acari. Monogeneans are the most dominant group, found in 14 caves. Macroparasites include species with direct life cycles and some trophically-transmitted parasites, including invasive species. Surprisingly, cave vs surface paired comparisons indicate higher parasite richness in the caves. The spatial variation in parasite composition across the caves suggests historical and geographical contingencies of the host-parasite colonization and the potential evolution of local adaptations. Base-line data on parasite diversity of cavefish populations ofA. mexicanussets the ground to explore the role of divergent parasite infections under contrasting ecological pressures (cave vs. surface environments) in the evolution of cave adaptive traits.
How to Scan DNA using Promiscuous Recognition and No Sliding Clamp: A Model for Pioneer Transcription Factors
Authors: Goluguri Rama Reddy , Sadqi Mourad , Nagpal Suhani , Muñoz Victor
Published: May 2023

DNA scanning proteins slide on the DNA assisted by a clamping interface and uniquely recognize their cognate sequence motif. The transcription factors that control cell fate in eukaryotes must forgo these elements to gain access to both naked DNA and chromatin, so whether or how they scan DNA is unknown. Here we use single-molecule techniques to investigate DNA scanning by the Engrailed homeodomain (enHD) as paradigm of promiscuous recognition and open DNA interaction. We find that enHD scans DNA as fast and extensively as conventional scanners and 10,000,000 fold faster than expected for a continuous promiscuous slide. Our results indicate that such supercharged scanning involves stochastic alternants between local sequence sweeps of ∼85 bp and very rapid deployments to locations ∼500 bp afar. The scanning mechanism of enHD reveals a strategy perfectly suited for the highly complex environments of eukaryotic cells that might be generally used by pioneer transcription factors.

Teaser

Eukaryotic transcription factors can efficiently scan DNA using a rather special mechanism based on promiscuous recognition.