bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Respiratory Distress Syndrome During the COVID-19 Era
Authors: White Cole J. , White Bailey Slone , Wadhwa Sanju R. , Aouad Arlette
Published: January 2022

During the current pandemic, the 2019 novel coronavirus (SARS-CoV-2) has quickly moved to the top of the list of potential causes of acute respiratory distress syndrome (ARDS) in patients presenting to the hospital. Potential COVID-19 infections should continue to be quickly identified and treated when indicated, but it is important that we not forget about the other potential causes of ARDS. In this case series, we will discuss 3 cases of ARDS that were passed off as likely SARS-CoV-2 infections but were all discovered to be negative for COVID-19. This highlights the importance of maintaining a thorough history and physical examination during the pandemic to identify the other causes of ARDS and avoid the negative effects of frequency bias.
Trends in Antimicrobial Allergies in Patients Seen in Infectious Disease Consultation During Selected Periods 2007–2016
Authors: Liu Hans H. , Mutneja Hemant , Buckley Meghan , Cushinotto Lisa
Published: January 2022

Background

Antimicrobial allergies and adverse reactions limit patient treatment options. “Antibiotic allergy” labeling drives broader, more toxic, and/or parenteral therapy. Published allergy data may be decades old over which time antibiotic usage has changed with newer agents introduced and greater use of several older ones. Some patient allergy designations are inaccurate; many are not true hypersensitivity. Electronic health records (EHRs) promote collection of allergy information but could inflate numbers as data are repetitively elicited and recorded.

Objectives

This study measured antimicrobial allergy prevalence in hospitalized adults and determined how EHR implementation affected data.

Methods

Retrospective chart reviews were conducted on 750+ adults seen in community teaching hospital infectious diseases consultation during each of three 6-month periods in 2007–2008, 2011–2012, and 2015–2016. Dates correspond to pre-EHR, after nursing data entry started, and after physician order entry and full electronic recordkeeping. Total antibiotic and nonantibiotic allergies were compiled and factors in recording these tracked.

Results

Penicillin (20.5%–22%), cephalosporin (8%–10.2%), sulfa (12%–14.1%), and fluoroquinolone (5.4%–8.9%) allergy frequencies were high. Antibiotic allergy rates were stable from 2007–2008 to 2015–2016 due to most repetitive listings being made “inactive.” However, median total drug allergies rose from 0 to 1 per patient (P < 0.01) and multiple drug intolerance (>3 unrelated drugs) increased.

Conclusions

Overall allergy rates for several antimicrobials were high but stable over study period; nonantibiotic allergies rose. Multidisciplinary allergy documentation is crucial in accurate data collection. Antibiotic-allergic and multiple drug intolerant patients are a good focus for prospective allergy education and “delabeling” programs.
Effects of Emergency Duties on Cardiovascular Diseases in Firefighters
Authors: Jeung Da-Yee , Hyun Dae-Sung , Kim Inah , Chang Sei-Jin
Published: January 2022

Objectives

This study aimed to examine the effects of firefighters’ emergency duties on the incidence of cardiovascular disease (CVD).

Methods

We used a 13-year follow-up in a nationwide retrospective cohort study. A total of 363,137 employees were recruited. The sex-and age-specific incidence of CVD (hypertension, angina pectoris, and acutemyocardial infarction [AMI]) in firefighters and public officials was estimated.

Results

The overall age-specific sex-based incidence of CVD, except for hypertension, was higher in firefighters than in public officials. The age-stratified hazard ratios for the three types of CVD in male firefighters were also higher. AMI was more common in younger firefighters, whereas angina pectoris and hypertension were common in older firefighters.

Conclusions

Firefighters’ duties are more likely to increase the risk of CVD, and preventive strategies with proven benefits are required.
Relationship Between Support for Workers With Illness and Work Functioning Impairment in Japan During the COVID-19 Pandemic
Authors: Igarashi Yu , Tateishi Seiichiro , Harada Arisa , Hino Ayako , Tsuji Mayumi , Ogami Akira , Mori Koji , Matsugaki Ryutaro , Fujino Yoshihisa
Published: January 2022

Objective:

This study examined the relationship between job accommodations for workers with poor health and work functioning impairment during the COVID-19 pandemic.

Methods:

An internet survey was conducted in December 2020. We included 24,429 subjects for analysis. One question was used to determine whether subjects needed job accommodations from their company to continue working in their current health condition. The odds ratios (ORs) of the necessity of job accommodations for sick workers associated with work functioning impairment were estimated using multilevel logistic regression analysis.

Results:

The OR of work functioning impairment among sick workers not receiving job accommodations was 5.75 (95% confidence interval (CI): 5.34 to 6.20, P 
< 0.001) and those receiving job accommodations was 1.88 (95% CI: 1.69 to 2.08, P 
< 0.001) compared to healthy workers.

Conclusions:

This study suggests that providing job accommodations to workers with poor health may improve their work functioning impairment.
The Laterality of Early Age-Related Hearing Loss and Brain β-Amyloid
Authors: Irace Alexandria L. , Rippon Brady Q. , Brickman Adam M. , Luchsinger José A. , Golub Justin S.
Published: January 2022

Objective:

Worse hearing was linked to higher brain β-amyloid, a pathologic hallmark of Alzheimer's disease, in a recent study. We analyze the associations between β-amyloid and early age-related hearing loss in the right versus left ear to explore the laterality of this relationship.

Study Design:

Cross-sectional analysis of a prospective cohort study.

Setting:

Tertiary referral center.

Participants:

Ninety-eight late middle-age adults.

Interventions:

None.

Main Outcome Measures:

The primary outcome was whole brain and regional β-amyloid standardized uptake value ratio (SUVR) on positron emission tomography. The exposure was hearing in the right and left ear, measured by pure tone average (PTA) and word recognition score (WRS). Linear regression analyzed the association between β-amyloid and hearing in each ear, adjusting for potential confounders, including age, gender, education, cardiovascular disease, and hearing aid use.

Results:

Mean age ± standard deviation was 64.3 ± 3.5 years. Mean PTA was 20.4 ± 8.8 dB. Multivariable regression adjusting for covariates demonstrated that a 10 dB worsening in PTA in the left ear was associated with significantly higher β-amyloid (SUVR) in the bilateral cingulate gyri (right coefficient: 0.029 [95% confidence interval: 0.003–0.054]; left: 0.029 [0.003–0.055]), bilateral frontal lobes (right: 0.024 [0.002–0.047]; left: 0.028 [0.006–0.049]), and the right temporal lobe (0.019 [0.002–0.037]). Consistent results were observed when WRS served as the exposure. No associations were observed between β-amyloid and PTA or WRS in the right ear.

Conclusions:

Worse hearing in the left ear, but not the right ear, was associated with higher β-amyloid. This might relate to asymmetric central auditory processing.
Pertussis vaccines
Authors: Cherry James D. , Doustmohammadi Saba
Published: January 2022

Purpose of review

Pertussis is a vaccine preventable cough illness. It can be controlled by universal pertussis vaccination.

Recent findings

Pertussis cases and deaths in children are at a record low number. More complete use of adolescent/adult vaccine can further reduce morbidity and mortality.

Considerable progress in the control of pertussis has occurred over the last 75 years. The universal use of Tdap vaccines in all pregnant women will prevent virtually all pertussis deaths.
Emollients to Prevent Eczema in High-Risk Infants
Authors: Armstrong Julie , Rosinski Nicole K. , Fial Alissa , Ansah Selorm , Haglund Kristin
Published: January 2022

The purpose of this integrative review was to assess the research on topical emollients to prevent atopic dermatitis (AD) also known as eczema, in infants at high risk for this condition. Atopic dermatitis is a common chronic inflammatory skin disorder. Skin barrier dysfunction plays a prominent role in its development. Topical emollients have been hypothesized to enhance the skin barrier and prevent AD.

Methods:

Searches were conducted in September 2021 in PubMed, CINAHL, Cochrane Library, and Web of Science using key word search terms dermatitis, atopic, emollients, petrolatum, and infant, newborn. Inclusion criteria were articles written in English published between 2010 and 2021 that tested emollients in high-risk infants and measured the development of AD.

Results:

Eight primary research articles were included. Six studies were limited by small sample sizes, short-term application of emollients, and short-term follow-up. These studies generated inconclusive results. Two large randomized controlled trials (RCTs) with a combined sample of 3,791 infants found no evidence that early, regular use of emollients prevents AD among high-risk infants.

Clinical Implications:

Findings from two high-quality RCTs indicate that clinicians should not recommend use of emollients to prevent AD. Clinicians may provide evidence-based recommendations for infant skin care, including bathe with water or a combination of water and liquid cleanser formulated for infants, and avoid soaps. Products applied to skin should be free of scent and contact allergens. Petroleum jelly or mineral oil is appropriate to moisturize infants' skin as needed.
Meeting Theory-to-Practice Gaps? Evaluation of New Graduates
Authors: Thomas Daphne , Merrill Katreena
Published: January 2022

For decades, nursing graduates have exhibited a gap between theory and practice. Healthcare organizations have implemented transition programs to support successful entry into practice. Nurse educators can restructure residency programs to help graduates develop the confidence and competence needed for practice by identifying the gaps between theory and practice for nursing graduates. This study’s findings support continual process improvement through evaluation and contribute to the literature about the challenges new nurses encounter.
Epidemiology of Pediatric Foreign Body Ingestions Amidst the Coronavirus 2019 Pandemic at a Tertiary Care Children’s Hospital
Authors: Klein Lauren J. , Black Katherine , Dole Michael , Orsagh-Yentis Danielle K.
Published: January 2022

Objectives:

The coronavirus disease (COVID) 2019 pandemic and resultant stay-at-home orders altered caregivers’ responsibilities and children’s daily environments. We aimed to compare the epidemiology and morbidity of foreign body ingestions (FBIs) during the COVID pandemic and the prior year.

Methods:

We performed a retrospective review of children cared for at our tertiary care children’s hospital for FBI from March to July 2019 (pre-COVID) and March to July 2020 (COVID). Cases were identified via a search of all diagnoses of foreign bodies (FBs) in the alimentary tract. Charts were reviewed to determine the types of FBs ingested and the patients’ clinical courses.

Results:

A total of 71 encounters were identified. Thirty ingestions occurred in the pre-COVID cohort and 42 in the COVID cohort. One patient ingested 2 different FBs. There was a significantly higher rate of FBIs per day in May 2020 (COVID) compared with May 2019 (pre-COVID; 0.387 versus 0.161; P = 0.046). The median age at presentation was not significantly different between the two groups (pre-COVID, 63.8 months; COVID, 62.5 months; P = 0.78). FBs were located in the esophagus less frequently in the COVID cohort than in the pre-COVID cohort (P < 0.01). Endoscopies were less frequently performed in the COVID cohort (52.4% versus 70.0%; odds ratio, 0.47; 95% CI, 0.15–1.40).

Conclusions:

The frequency of FBIs trended higher in the COVID cohort, with significantly more FBIs in May 2020 when compared with May 2019. Patients in the COVID cohort more frequently had FBs located beyond the esophagus, indicating later presentation and a lesser need for urgent endoscopic removal.
Low-grade Neuroendocrine Tumor of the Cervix: Report of 3 Cases of a Rare Neoplasm With Review of the Literature
Authors: Sah Shatrughan , Borkar Pallavi V. , Wight Catherine , Kelly Paul , Park Kay J. , McCluggage W. Glenn
Published: January 2022

Neuroendocrine neoplasms are uncommon in the cervix with almost all representing neuroendocrine carcinomas (NECs), either small cell or large cell type. Cervical low-grade neuroendocrine tumors (NETs) are extremely rare with few recent reports using contemporary modern diagnostic criteria. We report 3 cases of cervical NET in patients aged 32 to 57 yr and undertake a review of the literature. The first case was a pure grade 2 NET with pelvic lymph node metastasis (FIGO stage IIIC1). In the second case, a grade 1 NET was associated with high-grade squamous intraepithelial lesion, adenocarcinoma in situ and human papillomavirus (HPV)-associated adenocarcinoma and was FIGO stage IA1. The third patient underwent chemoradiotherapy following a biopsy diagnosis of a high-grade NEC which was radiologically FIGO stage IIIC1 and salvage hysterectomy revealed residual tumor with features of a grade 1 NET. In all cases, the NET was diffusely positive with at least 2 of the neuroendocrine markers chromogranin, synaptophysin, and CD56. The first tumor was p16 negative and the third exhibited block-type immunoreactivity. Molecular tests revealed high risk HPV types 18 and 51 in the third case but no HPV in the first case. p16 immunohistochemistry and HPV molecular testing was not available in the second case. The patients remain disease free with follow-up ranging from 2 to 8 yr. Since a combination of NET and NEC is extremely rare at all sites due to a different pathogenesis, we speculate that in the third case, the NET developed out of the NEC as a “maturation” phenomenon secondary to chemoradiotherapy.
High-grade Endometrial Carcinoma With a Hepatoid Carcinoma-like Component
Authors: Nishida Kenji , Toji Tomohiro , Taniguchi Kohei , Shibata Rei , Ono Sawako , Tanaka Takehiro , Yoshino Tadashi , Yanai Hiroyuki
Published: January 2022

Endometrial carcinoma with hepatoid differentiation is rare and <20 reported cases have been reported as endometrial hepatoid carcinoma (EHC). We present a case of EHC associated with serous carcinoma in a 76-yr-old Japanese woman. The hepatoid component showed trabecular, pseudoglandular, and diffuse proliferation of hepatoid cells. The hepatoid cells were positive for α-fetoprotein, Hep-Per-1, glypican 3, and HNF-1β, weakly and focally positive for SALL4, and negative for PAX8. Both of the serous and hepatoid components showed overexpression of p53. The serum α-fetoprotein on postoperative day 5 was 3691 ng/mL. The postoperative course has remained uneventful for 4 yr. These findings suggested that EHC developed from serous carcinoma by acquiring hepatocytic features and losing Müllerian features. Both serous and hepatoid components showed p53 overexpression, suggesting they share a TP53 mutation as a common primary driver.
A Quality Improvement Approach to Improving Discharge Documentation
Authors: Banker Sumeet L. , Lakhaney Divya , Hooe Benjamin S. , McCann Teresa A. , Kostacos Connie , Lane Mariellen
Published: January 2022

Introduction:

Accurate discharge documentation is critical to ensuring a safe and effective transition of care following hospitalization, yet many discharge summaries do not meet consensus standards for content. A local needs assessment demonstrated gaps in documentation of 3 essential elements: discharge diagnosis, discharge medications, and follow-up appointments. This study aimed to increase the completion of three discharge elements from a baseline of 45% by 20 percentage points over 16 months for patients discharged from the general pediatrics service.

Methods:

Ten discharge summaries were randomly selected and analyzed during each successive 2-week time period. Plan-Do-Study-Act cycles aimed to improve provider knowledge of essential discharge summary content, clarify communication during rounds, and create electronic health record shortcuts and quick-reference tools.

Results:

The percentage of discharge summaries containing all 3 required elements increased from 45% to 73%. Specifically, documentation increased for discharge diagnosis (65%–87%), discharge medications (71%–90%), and follow-up appointments (88%–93%). There was no significant delay in discharge summary completion.

Conclusions:

Discharge summaries are meaningfully and sustainably improved through provider education, workflows for clear communication, and electronic health record optimization.
Cost Implications of Varying the Surgical Setting and Anesthesia Type for Dorsal Wrist Ganglion Cyst Excision Surgery
Authors: Steadman Jesse N. , Stephens Andrew R. , Wei Guo , Presson Angela P. , Kazmers Nikolas H.
Published: January 2022

Background:

Minimizing expenses attributed to dorsal wrist ganglion cyst excisions, a common minor surgical procedure, presents potential for health care cost savings. Varying the surgical setting (operating room versus procedure room) and type of anesthesia (local-only, monitored anesthesia care, or monitored with regional or general anesthesia) may affect total operative costs.

Methods:

Patients who underwent an isolated unilateral dorsal wrist ganglion cyst excision between January of 2014 and October of 2019 at a single academic medical center were identified by CPT code. The total direct costs for each surgical encounter that met inclusion criteria were calculated. The relative total direct costs were compared between surgical setting and anesthesia type groups. Univariate and multivariable gamma regression models were used to identify factors associated with surgical costs.

Results:

A total of 192 patients were included; 26 cases (14 percent) were performed in the procedure room and 166 cases (86 percent) were performed in the operating room. No significant differences in demographic factors were identified between groups. Univariate analysis demonstrated that use of operating room/monitored anesthesia care, operating room/monitored anesthesia care with regional anesthesia, and operating room/general anesthesia groups, as compared to procedure room/local-only, yielded significantly greater median costs (1.76-, 2.34-, and 2.44-fold greater, respectively). Multivariable analysis demonstrated 1.80-, 2.10-, and 2.31-fold greater costs with use of operating room/monitored anesthesia care, operating room/monitored anesthesia care with regional anesthesia, and operating room/general anesthesia relative to procedure room/local-only, respectively.

Conclusion:

Performing dorsal wrist ganglion cyst excisions in a procedure room with local-only anesthesia minimizes operative direct costs relative to use of the operating room and other anesthetic types.
A Quantification of Scalp Thickness before and after Posterior Vault Distraction Osteogenesis
Authors: Zapatero Zachary D. , Morales Carrie Z. , Wes Ari M. , Kalmar Christopher L. , Kosyk Mychajlo S. , Swanson Jordan W. , Bartlett Scott P. , Taylor Jesse A.
Published: January 2022

Previous literature has documented craniometric changes of the bony calvaria, increases in intracranial volume, and resolution of Chiari malformations following posterior vault distraction osteogenesis. No studies have analyzed changes to the soft-tissue envelope after posterior vault distraction osteogenesis. In this study, the authors aimed to provide objective measurements of scalp thickness in patients undergoing posterior vault distraction osteogenesis, utilizing facial soft-tissue thickness as a proxy to control for growth. The authors hypothesized that the soft tissues of the scalp are not made thinner by the distraction process, either in the region of distraction or in neighboring areas. Subjects who underwent posterior vault distraction osteogenesis for a craniosynostosis diagnosis who had high-resolution predistraction and post–distractor removal computed tomographic scans within 100 days of each operation were included. The scans were analyzed on Materialise Mimics version 21 software (Materialise, Ghent, Belgium). Six key craniometric landmarks (glabella, pogonion, zygion, vertex, euryon, and opisthocranium) were identified on the three-dimensional bone masks in the Frankfort horizontal plane. The points were overlaid onto soft-tissue thickness masks and thicknesses were recorded. Percent change in postoperative facial soft-tissue thickness was used to control for growth of the craniofacial soft-tissue envelope during the study interval. The preoperative and postoperative posterior vault distraction osteogenesis cohorts did not differ significantly at the glabella, pogonion, opisthocranium, vertex, and zygion. The corrected median thickness at the euryon was significantly increased in the post–posterior vault distraction osteogenesis cohort [2.67 mm (IQR, 2.49 mm to 4.02 mm) versus 5.26 mm (IQR, 3.83 mm to 7.82 mm),p= 0.002]. This is the first study to quantify changes in soft-tissue thicknesses preoperatively and postoperatively in patients undergoing posterior vault distraction osteogenesis, demonstrating maintenance of scalp thickness. 

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
An Evaluation of the Effect of Activation Methods on the Release of Growth Factors from Platelet-Rich Plasma
Authors: Smith Oliver J. , Talaat Selim , Tomouk Taj , Jell Gavin , Mosahebi Ash
Published: January 2022

Background:

Activation of platelets in platelet-rich plasma may improve growth factor release, thus enhancing regenerative properties. The authors investigated whether different methods of platelet-rich plasma activation affected growth factor release kinetics over time.

Methods:

Platelet-rich plasma from 20 healthy volunteers was processed by six different methods: (1) control (nonactivated); (2) activation with calcium chloride; (3) activation with calcium chloride and ethanol; (4) activation with calcium chloride and ethanol at 4°C; (5) activation with calcium chloride and ethanol with vitamin C; (6) activation with calcium chloride and ethanol with vitamin C at 4°C. Concentration of secreted vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and insulin-like growth factor over 24 hours was measured by immunoassay.

Results:

Calcium chloride–activated platelet-rich plasma produced significantly more insulin-like growth factor at 1 hour compared to cold and vitamin C platelet-rich plasma, and calcium chloride plus ethanol produced significantly more at 24 hours compared to vitamin C platelet-rich plasma. The addition of vitamin C reduced release of PDGF over time. Activation with calcium chloride and ethanol with or without cold temperature produced a gradual PDGF release as opposed to calcium chloride alone, which caused higher PDGF within 4 hours. There were no significant differences between groups for VEGF, although calcium chloride and cooled platelet-rich plasma approached significance for producing more than vitamin C platelet-rich plasma.

Conclusions:

Activation of platelet-rich plasma does not significantly improve growth factor secretion, which is made worse by the addition of vitamin C, a platelet inhibitor. Ethanol does not negatively impact growth factor production and may offer a more gradual release.

Clinical Relevance Statement:

These findings will help guide platelet-rich plasma preparation methods where therapeutic growth factors are used.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Long-Term Results of the Murawski Unilateral Cleft Lip Repair
Authors: Murawski Eugeniusz L. , Gawrych Elzbieta H. , Cutting Court B. , Sifakis Eftychios D. , Wang Qisi , Tao Yutian
Published: January 2022

Background:

In 1968, Ralph Millard published his “Millard II” method for repair of wide, complete unilateral cleft lip and nose deformity. In 1979, Murawski published a major modification of the Millard II procedure in Polish. This motif was taken up 8 years later by Mohler and 22 years later by Cutting. The Murawski variation on the Millard II procedure has become a dominant motif in unilateral cleft lip repair worldwide. This brief report intends to introduce the method to the English language literature and present long-term results.

Methods:

The Murawski method alters the Millard II procedure by changing the upper medial curve into a point in the columellar base. This creates a broad C flap used to fill the entire defect produced by downward rotation of the medial lip. Millard’s lateral advancement flap becomes unnecessary. A lateral approach to primary nasal reconstruction allows the lateral C flap to be used to construct the nasal floor and sill. The method is described using a physics-based surgical simulator.

Results:

Long-term results of the method are demonstrated with four patients with 15 to 25-year follow-up. None of these patients had any revisions to the lip or nose.

Conclusions:

The Murawski repair was the first to modify the Millard II repair by sharpening the medial columellar incision, eliminating the need for a lateral advancement flap. This motif was put forth in the years to follow by Mohler and Cutting. Long-term results of the method are presented.
Releasing the Smile: Depressor Anguli Oris Excision in the Context of Managing Nonflaccid Facial Palsy
Authors: Derakhshan Adeeb , Miller Matthew Q. , Malka Ronit , Gadkaree Shekhar K. , Hadlock Tessa A.
Published: January 2022

Background:

Nonflaccid facial palsy is a debilitating entity characterized by hypertonicity, synkinesis, and hypomobility. Patients with nonflaccid facial palsy often have smile asymmetry and restriction because of disruption of normal vector forces on the modiolus. Excision of the depressor anguli oris can lead to improved oral commissure excursion, smile angle, dental show, and symmetry.

Methods:

All depressor anguli oris resection cases between January 8, 2018, and December 26, 2019, were reviewed. Patients with postoperative photographs were included in this cohort study. Preoperative and postoperative photographs were analyzed using the Emotrics software program, and changes in oral commissure excursion, smile angle, and dental show were tracked. Clinician-graded facial palsy assessments and patient-reported outcome measures were compared preoperatively and postoperatively using the Electronic Facial Paralysis Assessment and Facial Clinimetric Evaluation Scale, respectively.

Results:

Forty-three patients were included in this study; 79 percent of patients underwent isolated depressor anguli oris resection. Depressor anguli oris resection led to a statistically significant increase in oral commissure median excursion, smile angle, and dental show [3.02 mm (p= 0.015), 1.70 degrees (p= 0.002), and 2.36 mm (p< 0.001), respectively]. Median Electronic Facial Paralysis Assessment and Facial Clinimetric Evaluation Scale instrument scores also improved [6.0 (p= 0.001) and 7.5 (p= 0.013), respectively]. Depressor anguli oris resection also led to more symmetric smiles. No correlation was seen between duration of follow-up and change in metrics.

Conclusion:

Depressor anguli oris resection is a minimal-risk procedure that frequently results in improved smile dynamics, smile symmetry, and quality of life in patients with nonflaccid facial palsy.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
99mTc-TRODAT-1 SPECT Revealed That Striatal Dopamine Transport Availability Significantly Decreases in Late Mid-Aged Healthy Taiwanese and Then Remains Stable
Authors: Yeh Skye Hsin-Hsien , Tsai Chi-Jung , Yu Tsung-Hsun , Chiang Yung-Hsiao , Lin Shinn-Zong , Peng Nan-Jing , Huang Wen-Sheng
Published: January 2022

Objectives

Neuroimaging studies in the past 20 years have documented an age-related decline in striatal dopamine transporters (DATs), which is a marker of dopaminergic neurodegeneration; however, concerns about ethnic variations in the decline in DAT with age have not been addressed. The purpose of this study was to assess the rate of striatal DAT loss in healthy Taiwanese adults using kit-based 99mTc-TRODAT-1, a radioligand for DAT SPECT.

Patients and Methods

Fifty healthy subjects (mean age ± SD, 63 ± 12 years; range, 30–80 years) were studied. 99mTc-TRODAT-1 was prepared from a lyophilized kit. Brain DAT SPECT imaging was acquired between 165 and 195 minutes postinjection (~740 MBq or 20 mCi) using a dual-head camera equipped with fan-beam collimators (Helix SPX; GE). Specific uptake in the striatum (ST), caudate nucleus (CA), and putamen (PU) were calculated from reconstructed transaxial slices at the level of maximal striatal activity. Occipital cortices were used as reference areas. Data were presented as specific binding ratios.

Results

Age had a significant moderate to large negative effect on striatal DAT, which declined by −25.7% ± 6.10% between the ages of 30 and 80 years, equivalent to 6.4% loss per decade. The rates of decline in the CA and PU were 6.9% and 7.3% per decade, respectively.

Conclusions

This study suggests ethnic variations may not significantly affect the age-related decline in DAT. The data generated in this study could also be used as a reference to estimate DAT loss/occupancy in patients with DAT-related diseases.
Orbital Volume and Axial Length Development in Individuals Ages 12 to 60 Years With Congenital Microphthalmia: A Retrospective Cohort Study
Authors: Zhang Ju , Hou Zhijia , Li Yang , Xian Junfang , Chang Qinglin , Li Dongmei
Published: January 2022

Objective:

To analyze the stimulating effect of axial length development on orbital volume development in patients (ages 12–60 years) with congenital microphthalmia.

Methods:

This retrospective cohort study included 43 patients (86 eyes) with congenital microphthalmia. Three-dimensional images of the orbit were generated from past computed tomography scans, and digital orbital volume and axial length measurements were taken. The patients were divided into four age groups for analyses. Paired t tests and one-way analysis of variance tests were used to compare orbital volume and axial length between the affected and unaffected eyes. Pearson correlation analyses and scatter plots were used to investigate the correlations between age, orbital volume, and axial length in the affected and unaffected eyes. Linear regression analysis was used to determine the association between orbital volume and axial length.

Results:

The mean orbital volume in the affected and unaffected eyes was 17.08 ± 2.88 and 20.80 ± 2.55 cm3, respectively. The mean axis length in the affected and the unaffected groups was 12.73 ± 3.54 and 23.84 ± 1.43 mm, respectively. Significant differences were observed among orbital (t = 13.538, P < 0.001) volume and axial length (t = 21.339, P < 0.001) in the affected and the unaffected groups. There were no significant differences in affected orbital volume (F = 0.527, P > 0.05), unaffected orbital volume (F = 1.628, P > 0.05), affected axial length (F = 0.946, P > 0.05), and unaffected axial length (F = 2.217, P > 0.05) among the four age groups. According to the Pearson correlations, there were no significant correlations between age and affected volume, unaffected volume, affected axis, and unaffected axis (r = 0.095, 0.097, 0.084, and 0.022, respectively; all P > 0.05). Orbital volume was moderately correlated with axial length in the affected and unaffected groups (r = 0.470 and 0.410, respectively; both P < 0.01). Linear regression analysis revealed that a 1 mm change in axis length was associated with a 0.38 cm3 and 0.73 cm3 change in orbital volume in the affected and unaffected groups, respectively.

Conclusions:

In individuals ages 12 to 60 years old with congenital microphthalmia, the effect of axis length on the orbital volume growth of the affected eye is only half that of the unaffected eye. The eyeball, orbital tissue, and craniofacial development all play an important role in the growth of orbital volume.
Geometrical characterization of active contraction pulses in epithelial cells using the two-dimensional vertex model
Authors: Pérez-Verdugo Fernanda , Reig Germán , Cerda Mauricio , Concha Miguel L. , Soto Rodrigo
Published: January 2022

Several models have been proposed to describe the dynamics of epithelial tissues undergoing morphogenetic changes driven by apical constriction pulses, which differ in where the constriction is applied, either at the perimeter or in the medial regions. To help discriminate between these models, we analyse the impact of where constriction is applied on the final geometry of the active contracted cell, using the two-dimensional vertex model. We find that medial activity, characterized by a reduction in the reference area, generates anisotropic cell shapes, whereas isotropic cell shapes are produced when the reference perimeter is reduced. When plasticity is included, sufficiently slow processes of medial contractile activity, compared with the characteristic times of elasticity and plasticity, cells can achieve less elongated shapes. Similarly, for perimeter activity, the highest level of contraction is achieved. Finally, we apply the model to describe the apical contractile pulses observed within the epithelial enveloping cell layer during the pre-epiboly of the annual killifish
Austrolebias nigripinnis
. The analysis of the cell shape changes allowed a global fit of all parameters of the vertex model, with the pulses being quantitatively captured using perimeter activity and area plasticity.
Clonal hematopoiesis and risk of chronic liver disease
Authors: Wong Waihay J. , Emdin Connor , Bick Alexander , Zekavat Seyedeh M. , Niroula Abhishek , Pirruccello James , Dichtel Laura , Griffin Gabriel , Uddin Md Mesbah , Gibson Christopher J. , Kovalcik Veronica , Lin Amy E. , McConkey Marie E , Vromman Amelie , Sellar Rob S. , Kim Peter G. , Agrawal Mridul , Weinstock Joshua , Long Michelle T. , Yu Bing , Banerjee Rajarshi , Nicholls Rowan C. , Kelly Matt , Loh Po-Ru , McCarroll Steve , Boerwinkle Eric , Vasan Ramachandran , Jaiswal Siddhartha , Johnson Andrew , Chung Raymond T. , Corey Kathleen , Levy Daniel , Ballantyne Christie ,   NHLBI TOPMed Hematology Working Group, Ebert Benjamin L. , Natarajan Pradeep
Published: January 2022

Chronic liver disease is a major public health burden worldwide. Despite various liver injury mechanisms, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis. We examined the association between clonal hematopoiesis of indeterminate potential (CHIP) and chronic liver disease in 58,358 individuals from four prospective cohorts with whole exome sequencing data (Framingham Heart Study, Atherosclerosis Risk in Communities Study, UK Biobank and Mass General Brigham Biobank). CHIP was associated with an increased risk of prevalent chronic liver disease (OR 2.70 CI 1.42, 5.16, p=0.002) and incident chronic liver disease (HR 2.01 CI 1.46, 2.79, p=0.001) from both alcoholic and nonalcoholic causes. Individuals with CHIP showed 75% greater odds of MRI detectable liver inflammation and fibrosis (5.9% versus 3.5%, p=0.007) compared to those without CHIP. To assess causality, Mendelian randomization analyses showed that genetic predisposition to CHIP was associated with a greater risk of chronic liver disease (OR 2.37 CI 1.57, 3.6, p<0.001). In a dietary model of nonalcoholic steatohepatitis (NASH), mice transplanted with Tet2-deficient hematopoietic cells demonstrated more severe liver inflammation and fibrosis. These effects were mediated via NLRP3 inflammasome and increased downstream inflammatory cytokine expression, including IL6. In summary, clonal hematopoiesis is associated with an elevated risk of liver inflammation and chronic liver disease progression via an aberrant inflammatory response.
Beyond Prior and Volatility: The Distinct Iterative Updating Account of ASD
Authors: Shi Zhuanghua , Allenmark Fredrik , Theisinger Laura A. , Pistorius Rasmus L. , Glasauer Stefan , Müller Hermann J. , Falter-Wagner Christine M.
Published: January 2022

The nature of predictive-processing differences between individuals with autism spectrum disorder (ASD) and typically developing (TD) individuals is widely debated. Some studies suggest impairments in predictive processing in ASD, while others report intact processes, albeit with atypical learning dynamics. Here, we assessed duration reproduction tasks in high- and low-volatility settings to examine the updating dynamics of prior beliefs and sensory estimates. Employing a two-state Bayesian model, we differentiated how individuals with ASD and TD controls update their priors and perceptual estimates, and how these updates affect long-term prediction and behavior. Our findings indicate that individuals with ASD use prior knowledge and sensory input similarly to TD controls in perceptual estimates. However, they place a greater weight on sensory inputs specifically for iteratively updating their priors. This distinct approach to prior updating led to slower adaptation across trials; individuals with ASD relied less on their priors in perceptual estimates during the first half of sessions but achieved comparable integration weights as TD controls by the end of the session. By differentiating these aspects, our study highlights the importance of considering inter-trial updating dynamics to reconcile diverse findings of predictive processing in ASD. In consequence to the current findings, we suggest the distinct iterative updating account of predictive processing in ASD.

Significance Statement

Research on predictive processing in Autism Spectrum Disorder (ASD) remains controversial. The current study employed a two-state Bayesian model in varied volatility settings to explore inter-trial updating dynamics in ASD compared to typically developing (TD) peers. We found that individuals with ASD, while utilizing prior knowledge similarly to TD controls, place a disproportionate emphasis on sensory inputs when updating their priors. This unique pattern of slower adaptation during iterative updating leads to significant behavioral differences in the first half of trials between the two groups, but comparable levels by the end of the session. These findings not only highlight the importance of considering different timescales and dynamic updating processes in ASD, but also suggest that the predictive processing framework in ASD involves unique prior updating mechanisms that is likely associated with increased sensory reliance.
Nasally-delivered interferon-λ protects mice against upper and lower respiratory tract infection of SARS-CoV-2 variants including Omicron
Authors: Chong Zhenlu , Karl Courtney E. , Halfmann Peter J. , Kawaoka Yoshihiro , Winkler Emma S. , Yu Jinsheng , Diamond Michael S.
Published: January 2022

Although vaccines and monoclonal antibody countermeasures have reduced the morbidity and mortality associated with SARS-CoV-2 infection, variants with constellations of mutations in the spike gene threaten their efficacy. Accordingly, antiviral interventions that are resistant to further virus evolution are needed. The host-derived cytokine IFN-λ has been proposed as a possible treatment based on correlative studies in human COVID-19 patients. Here, we show IFN-λ protects against SARS-CoV-2 B.1.351 (Beta) and B.1.1.529 (Omicron)variants in three strains of conventional and human ACE2 transgenic mice. Prophylaxis or therapy with nasally-delivered IFN-λ2 limited infection of historical or variant (B.1.351 and B.1.1.529) SARS-CoV-2 strains in the upper and lower respiratory tracts without causing excessive inflammation. In the lung, IFN-λ was produced preferentially in epithelial cells and acted on radio-resistant cells to protect against of SARS-CoV-2 infection. Thus, inhaled IFN-λ may have promise as a treatment for evolving SARS-CoV-2 variants that develop resistance to antibody-based countermeasures.
Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons
Authors: Chaguza Chrispin , Coppi Andreas , Earnest Rebecca , Ferguson David , Kerantzas Nicholas , Warner Frederick , Young H. Patrick , Breban Mallery I. , Billig Kendall , Koch Robert Tobias , Pham Kien , Kalinich Chaney C. , Ott Isabel M. , Fauver Joseph R. , Hahn Anne M. , Tikhonova Irina R. , Castaldi Christopher , De Kumar Bony , Pettker Christian M. , Warren Joshua L. , Weinberger Daniel M. , Landry Marie L. , Peaper David R. , Schulz Wade , Vogels Chantal B.F. , Grubaugh Nathan D.
Published: January 2022

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continues to shape the coronavirus disease 2019 (Covid-19) pandemic. The detection and rapid spread of the SARS-CoV-2 ‘ Omicron’ variant (lineage B.1.1.529) in Botswana and South Africa became a global concern because it contained 15 mutations in the spike protein immunogenic receptor binding domain and was less neutralized by sera derived from vaccinees compared to the previously dominant Delta variant. To investigate if Omicron is more likely than Delta to cause infections in vaccinated persons, we analyzed 37,877 nasal swab PCR tests conducted from 12-26 December 2021 and calculated the test positivity rates for each variant by vaccination status. We found that the positivity rate among unvaccinated persons was higher for Delta (5.2%) than Omicron (4.5%). We found similar results in persons who received a single vaccine dose. Conversely, our results show that Omicron had higher positivity rates than Delta among those who received two doses within five months (Omicron = 4.7% vs. Delta = 2.6%), two doses more than five months ago (4.2% vs. 2.9%), and three vaccine doses (2.2% vs. 0.9%). Our estimates of Omicron positivity rates in persons receiving one or two vaccine doses were not significantly lower than unvaccinated persons but were 49.7% lower after three doses. In comparison, the reduction in Delta positivity rates from unvaccinated to 2 vaccine doses was 45.6-49.6% and to 3 vaccine doses was 83.2%. Despite the higher positivity rates for Omicron in vaccinated persons, we still found that 91.2% of the Omicron infections in our study occurred in persons who were eligible for 1 or more vaccine doses at the time of PCR testing. In conclusion, escape from vaccine-induced immunity likely contributed to the rapid rise in Omicron infections.
Evaluate the risk in conventional IVF frozen human blastocysts undergoing PGT using a new quantification method for parental contamination testing (qPCT)
Authors: Dong Yunqiao , Liu Dun , Zou Yangyun , Wan Cheng , Chen Chuangqi , Dong Mei , Huang Yuqiang , Huang Cuiyu , Weng Huinan , Zhu Xiulan , Wang Fang , Jiao Shujing , Liu Na , Lu Sijia , Zhang Xiqian , Liu Fenghua
Published: January 2022

Objective

To establish a method to assess risks associated with preimplantation genetic testing (PGT) in embryos simultaneously with adhered sperm and cumulus cells.

Design

A prospective pilot study.

Setting

University teaching hospital.

Patient(s)

120 frozen blastocysts that could be biopsied from 34 patients who had experienced repeated implantation failure or abortion due to chromosomal abnormalities after embryos transfer in prior routine IVF cycles.

Intervention(s)

Chromosome screening and parental DNA contamination testing was performed in the surplus frozen IVF blastocysts from 34 patients.

Main Outcome Measure(s)

Parental DNA contamination rate and euploidy rate in biopsied blastocysts.

Result(s)

A new quantification method for parental contamination testing (qPCT) in single-cell whole-genome amplification (WGA) products based on allelic ratio analysis was established and validated in an artificial model by comparing 22 results obtained before and after adding different numbers of sperm and cumulus cells to biopsied TE cells. The results of the prospective clinical study of qPCT-PGT-A showed that the maternal contamination rate was 0.83% (1/120) and the risk of paternal contamination was negligible. The euploidy rate in these blastocysts was 47.50% (57/120), and 21 frozen embryo transfer (FET) cycles resulted in ten ongoing clinical pregnancies and four healthy births.

Conclusion(s)

The evidence we provide in the study shows a low risk of PGT in embryos simultaneously with adhered sperm and cumulus cells. The qPCT assay can be used to detect the risk of potential contamination and ensure the accuracy of PGT results, thereby improving the clinical outcome of IVF.

Capsule

During PGT for human frozen conventional IVF embryos, paternal source pollution is negligible, while maternal pollution can not be ignored. qPCT method can effectively detect the parent DNA contamination in WGA products of biopsied TE cells.
Identification of age-associated transcriptomic changes linked to immunotherapy response in primary melanoma
Authors: Zowalaty Ahmed Ezat El
Published: January 2022

Melanoma is a lethal form of skin cancers that develops due to constitutive activation of MAPK signaling pathway driven by BRAF and NRAS mutations. Immunotherapeutic agents such as anti-PD-1 (pembrolizumab and nivolumab) and anti-CTLA-4 (ipilimumab) have revolutionized melanoma treatment, however drug resistance is rapidly acquired. Several studies reported the increase in melanoma rates in older patients. Thus, the impact of ageing on transcriptional profiles of melanoma and response to immunotherapy is essential to understand. In this study, bioinformatic analysis of RNA seq data of old and young melanoma patients receiving immunotherapy identified significant upregulation of extracellular matrix and cellular adhesion genes in young cohorts while genes involved in cell proliferation, inflammation, non-canonical Wnt signaling and tyrosine kinase receptor ROR2 were significantly upregulated in the old cohort. Several Treg signature genes as well as transcription factors that are associated with dysfunctional T cell tumor infiltration, were differentially expressed. Differential expression of several genes involved in oxidative phosphorylation, glycolysis and glutamine metabolism has been observed as well. Taken together, this study provides novel findings on the impact of ageing on transcriptional changes during melanoma and novel therapeutic targets for future studies.
Muscle and Adipose Tissue Segmentations at the C3 Vertebral Level for Sarcopenia-Related Clinical Decision-Making in Patients with Head and Neck Cancer
Authors: Wahid Kareem A. , Olson Brennan , Jain Rishab , Grossberg Aaron J. , El-Habashy Dina , Dede Cem , Salama Vivian , Abobakr Moamen , Mohamed Abdallah S.R. , He Renjie , Jaskari Joel , Sahlsten Jaakko , Kaski Kimmo , Fuller Clifton D. , Naser Mohamed A.
Published: January 2022

The accurate determination of sarcopenia is critical for disease management in patients with head and neck cancer (HNC). Quantitative determination of sarcopenia is currently dependent on manually-generated segmentations of skeletal muscle derived from computed tomography (CT) cross-sectional imaging. This has prompted the increasing utilization of machine learning models for automated sarcopenia determination. However, extant datasets of head and neck CT imaging currently do not provide the necessary manually-generated skeletal muscle segmentations at the C3 vertebral level needed for building these models. In this data descriptor, we detail the annotation of a large set of head and neck CT images for use in automated sarcopenia-related clinical decision making and body composition analysis. A set of 394 HNC patients were selected from The Cancer Imaging Archive, and their skeletal muscle and adipose tissue was manually segmented at the C3 vertebral level using sliceOmatic in .tag format. Subsequently, using publicly disseminated Python scripts, we generated corresponding segmentations files in Neuroimaging Informatics Technology Initiative format. In addition to segmentation data, additional clinical demographic data germane to body composition analysis have been retrospectively collected for these patients from the University of Texas MD Anderson Cancer Center databases. These data are a valuable resource for studying sarcopenia and body composition analysis in patients with HNC.