bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant Fibrin Clot Structure Visualized Ex Vivo in Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection
Authors: Brubaker Lisa S. , Saini Arun , Nguyen Trung C. , Martinez-Vargas Marina , Lam Fong W. , Yao Qizhi , Loor Michele M. , Rosengart Todd K. , Cruz Miguel A. 
Published: February 2022

OBJECTIVES:
Disseminated fibrin-rich microthrombi have been reported in patients who died from COVID-19. Our objective is to determine whether the fibrin clot structure and function differ between critically ill patients with or without COVID-19 and to correlate the structure with clinical coagulation biomarkers.

DESIGN:
A cross-sectional observational study. Platelet poor plasma was used to analyze fibrin clot structure; the functional implications were determined by quantifying clot turbidity and porosity.

SETTING:
ICU at an academic medical center and an academic laboratory.

PATIENTS:
Patients admitted from July 1 to August 1, 2020, to the ICU with severe acute respiratory syndrome coronavirus 2 infection confirmed by reverse transcription-polymerase chain reaction or patients admitted to the ICU with sepsis.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Blood was collected from 36 patients including 26 ICU patients with COVID-19 and 10 ICU patients with sepsis but without COVID-19 at a median of 11 days after ICU admission (interquartile range, 3–16). The cohorts were similar in age, gender, body mass index, comorbidities, Sequential Organ Failure Assessment (SOFA) score, and mortality. More patients with COVID-19 (100% vs 70%; p = 0.003) required anticoagulation. Ex vivo fibrin clots formed from patients with COVID-19 appeared to be denser and to have smaller pores than those from patients with sepsis but without COVID-19 (percent area of fluorescent fibrin 48.1% [SD, 16%] vs 24.9% [SD, 18.8%]; p = 0.049). The turbidity and flow-through assays corroborated these data; fibrin clots had a higher maximum turbidity in patients with COVID-19 compared with patients without COVID-19 (0.168 vs 0.089 OD units; p = 0.003), and it took longer for buffer to flow through these clots (216 vs 103 min; p = 0.003). In patients with COVID-19, d-dimer levels were positively correlated with percent area of fluorescent fibrin (ρ = 0.714, p = 0.047). Denser clots (assessed by turbidity and thromboelastography) and higher SOFA scores were independently associated with delayed clot lysis.

CONCLUSIONS:
We found aberrant fibrin clot structure and function in critically ill patients with COVID-19. These findings may contribute to the poor outcomes observed in COVID-19 patients with widespread fibrin deposition.
A broadly neutralizing human monoclonal antibody against the hemagglutinin of avian influenza virus H7N9
Authors: Li Jingxin , Zhang Li , Bao Linlin , Wang Yuxiao , Qiu Lin , Hu Jialei , Tang Rong , Yu Huiyan , Shan Jun , Li Yan , Qin Chuan , Zhu Fengcai 
Published: February 2022

Abstract

Background:
The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9.

Methods:
H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.

Results:
The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID50) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.

Conclusion:
The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.
Association between sex hormone-binding globulin and kidney function in men: results from the SPECT-China study
Authors: Zhang Haojie , Chen Chi , Zhang Xuan , Wang Yuying , Wan Heng , Chen Yi , Zhang Wen , Xia Fangzhen , Lu Yingli , Wang Ningjian 
Published: February 2022

Abstract

Background:
The association between sex hormone-binding globulin (SHBG) and renal function has rarely been reported in men. We aimed to investigate the above association in a community-based Chinese population.

Methods:
A total of 5027 men were included from the survey on prevalence for metabolic diseases and risk factors, which is a population-based study conducted from 2014 to 2016 in Eastern China. The estimated glomerular filtration rate (eGFR) was calculated according to the chronic kidney disease Epidemiology Collaboration equation. Low eGFR was defined as eGFR <60 mL·min−1·1.73 m−2.

Results:
After adjusting for age, smoking, metabolic factors, and testosterone, through increasing quartiles of SHBG, a significantly positive association between SHBG quartiles and eGFR was detected in men (Q1 vs. Q4, β −2.53, 95% confidence interval −3.89, −1.17, P
trend < 0.001). Compared with the highest quartile of SHBG, SHBG in the lowest quartile was associated with 96% higher odds of low eGFR (odds ratio 1.96, 95% confidence interval 1.10, 3.48) in the model after full adjustment. According to the stratified analyses, the associations between a 1-standard deviation increase in serum SHBG and the prevalence of low eGFR were significant in men aged ≥60 years old, waist circumference <90 cm, diabetes (no), hypertension (yes), dyslipidemia (no), and nonalcoholic fatty liver disease (no).

Conclusions:
Lower serum SHBG levels were significantly associated with lower eGFR and a higher prevalence of low eGFR in Chinese men independent of demographics, lifestyle, metabolic-related risk factors, and testosterone. Large prospective cohort and basic mechanistic studies are warranted in the future.
The Utility of Myoepithelial Cell Layer Identification in Adnexal Carcinomas
Authors: Plaza Jose A. , Chung Catherine , Wick Mark , Sangueza Martin , Gru Alejandro 
Published: February 2022

Abstract:
The distinction of metastatic carcinomas to the skin (MCS) from cutaneous adnexal carcinomas can pose a significant diagnostic challenge. The differentiation between (MCS) from a primary cutaneous adnexal tumor is one of the most difficult tasks in the field of dermatopathology, and immunohistochemistry has only been partially helpful in solving this problem. In routine diagnostic surgical pathology, it is essential to identify the myoepithelial cell layer by immunohistochemistry to distinguish between an in situ and invasive breast carcinomas and when establishing the presence of microinvasion. The purpose of this study was to evaluate the role of myoepithelial cell layer expression in difficult cases of cutaneous adnexal carcinomas in which histologically it was challenging to separate them from MCS. We studied 38 adnexal carcinomas and evaluated them for myoepithelial markers to confirm the primary nature of the neoplasm. The used markers to search for myoepithelial cell layer retention included calponin, p63, and smooth muscle actin. Of the 38 cases, we found that 13 cases showed myoepithelial layer retention, confirming the primary cutaneous origin of the neoplastic process. The results of our study suggest that the presence of an identifiable retention of the myoepithelial cell layer in adnexal carcinomas could be a useful adjunct observation in the diagnosis of primary adnexal carcinomas, especially in the clinical setting of a questionable primary adnexal versus metastatic neoplasm.
The Impact of Preinjury and Secondary Attention-Deficit/Hyperactivity Disorder on Outcomes After Pediatric Traumatic Brain Injury
Authors: Narad Megan E. , Kaizar Eloise E. , Zhang Nanhua , Taylor H. Gerry , Yeates Keith Owen , Kurowski Brad G. , Wade Shari L. 
Published: February 2022

ABSTRACT:

Objective:
The objective of this study was to examine the impact of preinjury attention-deficit/hyperactivity disorder (PADHD) and secondary ADHD (SADHD) on outcomes after pediatric traumatic brain injury (TBI).

Methods:
Two hundred eighty-four individuals aged 11 to 18 years hospitalized overnight for a moderate-to-severe TBI were included in this study. Parents completed measures of child behavior and functioning and their own functioning. Linear models examined the effect of ADHD status (PADHD vs SADHD vs no ADHD) on the child's executive functioning (EF), social competence, and functional impairment, and parental depression and distress.

Results:
ADHD status had a significant effect on EF [F(2,269] = 9.19, p = 0.0001), social competence (F[2,263] = 32.28, p < 0.0001), functional impairment (F[2,269] = 16.82, p < 0.0001), parental depression (F[2,263] = 5.53, p = 0.005), and parental distress (F[2,259] = 3.57, p = 0.03). PADHD and SADHD groups had greater EF deficits, poorer social competence, and greater functional impairment than the no ADHD group. The SADHD group had greater levels of parental depression than the no ADHD and PADHD groups, and the SADHD group had higher parental distress than the no ADHD group.

Conclusion:
The results highlight the importance of early identification and management of ADHD symptoms after injury to mitigate downstream functional problems. Supporting parents managing new-onset ADHD symptoms may also be important.
Muscarinic Receptor Activation Reduces Force and Arrhythmias in Human Atria Independent of IK,ACh
Authors: Petersen Johannes , Castro Liesa , Bengaard Anne K. P. , Pecha Simon , Ismaili Djemail , Schulz Carl , Sahni Jascha , Steenpass Anna , Meier Christian , Reichenspurner Hermann , Jespersen Thomas , Eschenhagen Thomas , Christ Torsten 
Published: February 2022

Abstract:
In human hearts, muscarinic receptors (M-R) are expressed in ventricular and atrial tissue, but the acetylcholine-activated potassium current (IK,ACh) is expressed mainly in the atrium. M-R activation decreases force and increases electrical stability in human atrium, but the impact of IK,ACh to both effects remains unclear. We used a new selective blocker of IK,ACh to elaborate the contribution of IK,ACh to M-R activation-mediated effects in human atrium. Force and action potentials were measured in rat atria and in human right atrial trabeculae. Cumulative concentration–effect curves for norepinephrine-induced force and arrhythmias were measured in the presence of carbachol (CCh; 1 µM) or CCh together with the IK,ACh –blocker XAF-1407 (1 µM) or in time-matched controls. To investigate the vulnerability to arrhythmias, we performed some experiments also in the presence of cilostamide (0.3 µM) and rolipram (1 µM), inhibiting PDE3 and PDE4. In rat atria and human right atrial trabeculae, CCh shortened the action potential duration persistently. However, the direct negative inotropy of CCh was only transient in human, but stable in rat atria. In rat and human atria, the negative inotropic effect was insensitive to blockage of IK,ACh by XAF-1407. In the presence of cilostamide and rolipram about 40% of trabeculae developed arrhythmias when exposed to norepinephrine. CCh prevented these concentration-dependent norepinephrine-induced arrhythmias, again insensitive to XAF-1407. Maximum catecholamine-induced force was not depressed by CCh. In human atrium, the direct and the indirect negative inotropic effect of CCh are independent of IK,ACh. The same applies to the CCh-mediated suppression of norepinephrine/PDE-inhibition-induced arrhythmias.
Effect of IL-1 Blockade With Anakinra on Heart Failure Outcomes in Patients With Anterior Versus Nonanterior ST Elevation Myocardial Infarction
Authors: Del Buono Marco Giuseppe , Damonte Juan Ignacio , Chiabrando Juan Guido , Markley Roshanak , Turlington Jeremy , Trankle Cory R. , Kang Le , Biondi-Zoccai Giuseppe , Van Tassell Benjamin W. , Abbate Antonio 
Published: February 2022

Abstract:
Patients with ST elevation myocardial infarction (STEMI) are at risk of future heart failure (HF), particularly those with anterior STEMI. Interleukin-1 (IL-1) is a key mediator of the inflammatory response, and its blockade has emerged as a potential therapeutic strategy to prevent HF events. The aim of this analysis was to explore the effects of anakinra, an IL-1 receptor antagonist, on HF outcomes based on anterior versus nonanterior location STEMI and to explore whether this effect is mediated through the amelioration of left ventricular systolic function and cardiac remodeling. We pooled data from 3 early phase randomized clinical trials. The primary end point was a composite of all-cause death and new-onset HF at 1-year follow-up. The left anterior descending coronary artery as culprit vessel was used to identify anterior STEMI. We included 139 patients, 47 (34%) with anterior STEMI and 92 (66%) with nonanterior STEMI. Anakinra significantly reduced the combined end point of death or new-onset HF in patients with anterior STEMI [4 (13%) vs. 7 (42%), log-rank P value = 0.049] and in patients with nonanterior STEMI [3 (6%) vs. 9 (24%), log-rank P value = 0.014]. We found no significant differences comparing anakinra versus placebo in interval changes in left ventricular ejection fraction and volumes in anterior and nonanterior STEMI. In conclusion, anakinra is associated with a reduction of HF events in patients with STEMI, irrespective of anterior or nonanterior location, or of changes in left ventricular ejection fraction or cardiac remodeling.
RP2 X-LINKED RETINITIS PIGMENTOSA CARRIER STATE PRESENTING WITH VASCULAR LEAKAGE AND UNILATERAL MACULAR ATROPHY
Authors: Raparia Eva , Ballios Brian G. , Place Emily M. , Husain Deeba , Huckfeldt Rachel M. 
Published: February 2022

Purpose:
We describe the unusual clinical presentation of a 33-year-old woman subsequently identified as a carrier of RP2-associated X-linked retinitis pigmentosa.

Methods:
Case report.

Results:
A 33-year-old woman without a known family history of retinal disease presented with unilateral reduced visual acuity and central scotoma in the left eye. Examination showed underlying macular atrophy in the left eye and a bilateral tapetal-like reflex. Full-field electroretinogram was abnormal in the left eye but normal in the right eye. Notable findings on wide-field imaging included bilateral peripheral vascular leakage on fluorescein angiography and a bilaterally symmetric radial pattern of hyperfluorescence on fundus autofluorescence. Genetic testing demonstrated a pathogenic variant in the gene RP2 confirming that she was a carrier of X-linked retinitis pigmentosa.

Conclusion:
We describe clinical features of the carrier state of RP2-XLRP and expand potential findings to include peripheral vascular leakage. This case highlights the importance of awareness of the carrier state, particularly if a family history cannot be provided.
Skin Cancer Back to Basics
Authors: Dhillon Soneet , Lake Eden 
Published: February 2022

ABSTRACT
Anogenital squamous cell carcinoma is rare but an often-invasive malignancy that is becoming an increasingly prevalent public health problem. Infection with high-risk human papillomavirus variants plays a critical role in disease progression and occurrence. Immunosuppressive treatment, positive HIV status, number of sexual partners, and history of smoking increase neoplastic progression. Early diagnosis and treatment are pivotal in managing anogenital malignancies to improve quality of life and minimize extensive surgical excision. This article reviews lesion categorization, epidemiology, human-papillomavirus-driven dysplastic epithelial changes, risk factors, diagnostic criteria, treatment options, and prophylactic measures to improve patient outcomes.
Physician Assistant Student Training in Question Formulation: A Quasi-Experiment
Authors: Eldredge Jonathan , Nogar Carmella 
Published: February 2022

Purpose
To measure improvement in evidence-based practice (EBP) question formulation skills in physician assistant (PA) students using a new approach that included a rubric.

Methods
Quasi-experiment study design featuring pre- and posttests in which the participants are their own controls using a paired t-test to measure skills improvement.

Results
Physician assistant students increased their skills in formulating EBP questions by a statistically significant margin.

Conclusions
This new approach to teaching EBP question formulation with its rubric offers a vehicle for training PA students in question formulation skills that is potentially more versatile than the conventional PICO (Population, Intervention, Comparison, and Outcomes) approach.
Pipeline to the Physician Assistant Profession: A Look to the Future
Authors: VanderMeulen Stephane , Snyder Jennifer A. , Kohlhepp William , Mustone Alexander Lisa , Straker Howard , Bowser Jonathan , Bondy Mary Jo 
Published: February 2022

Abstract:
The current pipeline of physician assistant (PA) school applicants reflects the future workforce of the profession, which is why the admissions process with all its components and variables is so important. Many studies have shown that a workforce that represents the patients it cares for leads to improved health outcomes, especially among underrepresented minority populations. Yet, PA programs have made little progress over the past 2 decades in increasing the diversity of matriculants and graduates. As a profession, it is our collective responsibility to intentionally advance diversity, equity, and inclusion, and examining the admissions process would be the most logical place to start.
The Effect of Sex, Sport, and Preexisting Histories on Baseline Concussion Test Performance in College Lacrosse and Soccer Athletes
Authors: Mihalik Jason P. , Teel Elizabeth F. , Ford Cassie B. , Amalfe Stephanie A. , Barczak-Scarboro Nikki E. , Lynall Robert C. , Riegler Kaitlin E. , Wasserman Erin B. , Putukian Margot 
Published: February 2022

Objective:
To study sex and sport differences in baseline clinical concussion assessments. A secondary purpose was to determine if these same assessments are affected by self-reported histories of (1) concussion; (2) learning disability; (3) anxiety and/or depression; and (4) migraine.

Design:
Prospective cohort.

Setting:
National Collegiate Athletic Association D1 Universities.

Participants:
Male and female soccer and lacrosse athletes (n = 237; age = 19.8 ± 1.3 years).

Assessment of Risk Factors:
Sport, sex, history of (1) concussion; (2) learning disability; (3) anxiety and/or depression; and (4) migraine.

Main Outcome Measures:
Sport Concussion Assessment Tool 22-item symptom checklist, Standardized Assessment of Concussion, Balance Error Scoring System (BESS), Generalized Anxiety Disorder 7-item scale, and Patient Health Questionnaire.

Results:
Female athletes had significantly higher total symptoms endorsed (P = 0.02), total symptom severity (P < 0.001), and BESS total errors (P = 0.01) than male athletes. No other sex, sport, or sex-by-sport interactions were observed (P > 0.05). Previous concussion and migraine history were related to greater total symptoms endorsed (concussion: P = 0.03; migraine: P = 0.01) and total symptom severity (concussion: P = 0.04; migraine: P = 0.02). Athletes with a migraine history also self-reported higher anxiety (P = 0.004) and depression (P = 0.01) scores. No other associations between preexisting histories and clinical concussion outcomes were observed (P > 0.05).

Conclusions:
Our findings reinforce the need to individualize concussion assessment and management. This is highlighted by the findings involving sex differences and preexisting concussion and migraine histories.

Clinical Relevance:
Clinicians should fully inventory athletes' personal and medical histories to better understand variability in measures, which may be used to inform return-to-participation decisions following injury.
Pharmacological Management of Heroin Withdrawal Syndrome
Authors: Manu Peter , Rogozea Liliana M. , Shulman Matisyahu 
Published: February 2022

Background:
Opioid use disorder continues to have a significant impact on public health morbidity and mortality throughout the United States and elsewhere. Managing opioid withdrawal is a critical treatment goal in individuals entering treatment with an active opioid use.

Study Question:
What are the milestones of the changes in the expert approach to the pharmacological management of heroin withdrawal syndrome in the past century?

Study Design:
To determine the changes in the expert approach to the management of heroin withdrawal syndrome, as presented in a widely used textbook in the United States.

Data Sources:
The chapters on opioid dependence in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020.

Results:
Opioid replacement taper with morphine (1927–1947), codeine (1931–1943), and methadone (1951–present) administered for 3–10 days has remained the main intervention. The anticholinergic drugs, scopolamine and atropine, were recommended from 1927 to 1943, but their use has never been backed by scientific evidence. Newer approaches relied on clonidine, an alpha-2 receptor agonist used since 1982, and buprenorphine, an opioid agonist/antagonist endorsed for the treatment of heroin withdrawal in 2000.

Conclusions:
The pharmacological management of heroin withdrawal syndrome in the past century has progressed from the introduction of methadone to the utilization of clonidine and buprenorphine. More recent advances in treating opioid use disorder have changed the goals of opioid withdrawal management to achievement of abstinence from all opioids to facilitation of long-term treatment with medications for opioid use disorder.