bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of ulinastatin on the inflammatory response after video-assisted thoracic lobectomy in patients with lung cancer: a randomized controlled study
Authors: Hwang Won Jung , Joo Min A. , Joo Jin
Published: January 2022

Background:

The first-line treatment for lung cancer is surgical resection, and one-lung ventilation (OLV) is the most basic anesthetic management method in lung surgery. During OLV, inflammatory cytokines are released in response to the lung tissue damage and promote local and contralateral lung damage through the systemic circulation. We designed a randomized, prospective study to evaluate the effect of the urinary trypsin inhibitor (UTI) ulinastatin on the inflammatory response after video-assisted thoracic lobectomy in patients with lung cancer.

Methods:

Adult patients aged 19 to 70 years, who were scheduled for video-assisted thoracic lobectomy surgery to treat lung cancer between May 2020 and August 2020, were enrolled in this randomized, prospective study. UTI (300,000 units) mixed with 100 mL of normal saline in the ulinastatin group and 100 mL of normal saline in the control group was administered over 1 h after inducing anesthesia.

Results:

The baseline (T0) interferon-γ (IFN-γ)/interleukin-4 (IL-4) ratio was not different between the groups (6941.3 ± 2778.7 vs. 6954.3 ± 2752.4 pg/mL, respectively; P 
> 0.05). The IFN-γ/IL-4 ratio was significantly higher in ulinastatin group at 30 min after entering the recovery room than control group (20,148.2 ± 5054.3 vs. 6674.0 ± 2963.6, respectively; adjusted P < 0.017).

Conclusion:

Administering UTI attenuated the anti-inflammatory response, in terms of INF-γ expression and the IFN-γ/IL-4 ratio, after video-assisted thoracic surgery in lung cancer patients.

Trial registration:

Clinical Research Information Service of Korea National Institute of Health (CRIS), KCT0005533.
The Biological Parallels Between Atherosclerosis and Cardiac Allograft Vasculopathy: Implications for Solid Organ Chronic Rejection
Authors: Otunla Afolarin A. , Shanmugarajah Kumaran , Davies Alun H. , Lucia Madariaga Maria , Shalhoub Joseph
Published: January 2022

Atherosclerosis and solid organ chronic rejection are pervasive chronic disease states that account for significant morbidity and mortality in developed countries. Recently, a series of shared molecular pathways have emerged, revealing biological parallels from early stages of development up to the advanced forms of pathology. These shared mechanistic processes are inflammatory in nature, reflecting the importance of inflammation in both disorders. Vascular inflammation triggers endothelial dysfunction and disease initiation through aberrant vasomotor control and shared patterns of endothelial activation. Endothelial dysfunction leads to the recruitment of immune cells and the perpetuation of the inflammatory response. This drives lesion formation through the release of key cytokines such as IFN-y, TNF-alpha, and IL-2. Continued interplay between the adaptive and innate immune response (represented by T lymphocytes and macrophages, respectively) promotes lesion instability and thrombotic complications; hallmarks of advanced disease in both atherosclerosis and solid organ chronic rejection. The aim of this study is to identify areas of overlap between atherosclerosis and chronic rejection. We then discuss new approaches to improve current understanding of the pathophysiology of both disorders, and eventually design novel therapeutics.
Association of the Effectiveness of Eye Drop Self-instillation and Glaucoma Progression
Authors: Rajanala Alekya P. , Prager Alisa J. , Park Meghan S. , Tanna Angelo P.
Published: January 2022

Précis:

Among patients with glaucoma or ocular hypertension, ineffective self-instillation of eye drops was associated with an increased long-term risk of progression or advancement of treatment to incisional surgery.

Purpose:

The purpose of this study was to evaluate the association between the efficacy of self-instillation of eye drops and long-term glaucoma outcomes.

Methods:

In a previous study, video recordings of eye drop self-instillation by patients with glaucoma or ocular hypertension were graded as effective or ineffective depending on whether the patient successfully instilled at least 1 drop on the right ocular surface. Glaucomatous progression was then retrospectively defined as retinal nerve fiber layer thinning as measured by either optical coherence tomography, visual field progression, or need for incisional glaucoma surgery as determined by a glaucoma specialist unaware of patient performance in the eye drop instillation study. Subjects with at least 2 follow-up optical coherence tomography or visual field studies were included in the current study.

Results:

The original study enrolled 119 patients. Sufficient follow-up data were available for 101 patients. Eighty-eight patients (87.1%) were effective in eye drop instillation at baseline. Mean follow-up was 5.1 years, during which time 73 patients (72.3%) had progression or underwent incisional surgery in either eye. A significantly higher proportion of patients in the ineffective group met the criteria for progression or underwent incisional surgery (effective: 68.2%; ineffective: 100%; N=101; P=0.017, Fisher exact test). Kaplan-Meier survival analyses showed a significantly faster time to reaching an endpoint in the ineffective group (N=101; P=0.012, log-rank test). There was no difference in age, baseline intraocular pressure, or baseline retinal nerve fiber layer thickness between the groups.

Conclusion:

Ineffective self-installation of eye drops was associated with an increased risk of glaucoma progression or treatment advancement to incisional surgery.
Does Note-taking Method Matter in Physical Therapy School?
Authors: Lorio Anne K. , Greenberg Daphne , Oshima T. C. , Gore Jane B. , Carruth Laura L.
Published: January 2022

Introduction.

Personal technology devices are now a primary method of note-taking in graduate learning. This study compared student learning outcomes using laptops for digital note-taking compared with handwritten notes.

Review of Literature.

Various results were reported in the literature of which note-taking method in undergraduate and graduate levels of learning results in best learning outcomes.

Subjects.

Subjects were 117 first-year doctoral physical therapy students enrolled in a 3-week wound care course. The study was completed over 3 consecutive years.

Methods.

Subjects volunteered to either use their laptop for digital note-taking or take handwritten notes on slide handouts. After course completion, course grades were compared between the 2 different note-taking method groups.

Results.

A 1-way analysis of variance yielded no significant difference due to the method of note-taking on overall course grade F(1, 115) = .048 (P = .827). A 2-way analysis of variance yielded no significant interaction between the method of note-taking and gender, but the main effect of gender was significant, with female subjects scoring higher than male subjects. Another 2-way analysis of variance yielded a significant interaction between the method of note-taking and the age of the student F(1, 113) = 9.402 (P = .003), and a simple main effects analysis for age found a significant difference in course grade between the 2 note-taking methods for older students F(1, 113) = 8.923 (P = .003) but not for younger students. This indicates that the effect of note-taking method on the course grade depended on the age group, specifically the older group tended to perform better with handwritten notes.

Discussion and Conclusion.

With our findings focusing on graduate physical therapy students, we found that handwritten note-takers tended toward having higher course grades, but they did not significantly outperform the digital note-taking group. Our findings found that the age of student and handwritten note-taking resulted in significantly higher course grades. Female gender was also found to be a significant factor for improved classroom performance in this study.

Important and Relevance of Work.

Results from this study indicated that modality of note-taking may not matter for most students, but it may matter for older students. Older students performed better in the handwritten notes group, and these findings are important to share with course instructors and with older students who may be struggling in graduate coursework.
Validity of the Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS) in Patients With Dizziness
Authors: Herdman David , Picariello Federica , Moss-Morris Rona
Published: January 2022

Hypothesis:

The Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS) will be a valid and reliable combined measure of depression and anxiety in people with vertigo and dizziness.

Background:

Co-occurrence of depressive, anxiety, and somatic symptoms are common. The Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder Scale-7 (GAD-7) measure symptoms of depression and anxiety respectively, although measuring them separately may be suboptimal in people who have illness-related distress. There is some evidence that these scales can be combined in long-term conditions resulting in the PHQ-ADS, but validity is yet to be determined in people with vertigo and dizziness.

Methods:

Two separate datasets from a tertiary vestibular clinic were analyzed where the PHQ-ADS was completed at initial clinical assessment (n = 624) and while on a waiting list (n = 185). A cross-sectional design was used to examine the factor structure (confirmatory factor analysis), internal consistency (omega index), and construct validity (Pearson correlation coefficient) of the PHQ-ADS. Construct validity was determined against the dizziness handicap inventory (DHI).

Results:

A bi-factor PHQ-ADS model had good fit to the data (χ2 = 397.163, 249.763; comparative fit index [CFI] = 0.954, 0.919; Tucker-Lewis index [TLI] = 0.938, 0.892; root mean squared error of approximation [RMSEA] = 0.076, 0.098). The general distress factor explained 81 to 85% of the common variance between items. There were moderate to large significant positive correlations between the PHQ-ADS and DHI.

Conclusion:

The PHQ-ADS appears to have good structural validity in patients with vertigo and dizziness. Clinicians and researchers can use this scale where a composite psychological measure is desired.
Hearing Outcomes of Transmastoid Plugging for Superior Canal Dehiscence Syndrome by Underwater Endoscopic Surgery: With Special Reference to Transient Bone Conduction Increase in Early Postoperative Period
Authors: Kawamura Yoshinobu , Yamauchi Daisuke , Kobayashi Toshimitsu , Ikeda Ryoukichi , Kawase Tetsuaki , Katori Yukio
Published: January 2022

Objective:

To investigate the influence on hearing of transmastoid plugging of the superior semicircular canal accompanied with membranous superior canal transection by underwater endoscopic ear surgery (UWEES) for the superior semicircular canal dehiscence syndrome.

Study Design:

Retrospective case review.

Setting:

Tertiary referral center.

Patients:

Seven patients underwent plugging with membranous superior canal transection with UWEES from 2017 to 2019.

Intervention:

Bone conduction (BC) thresholds (250, 500, 1000, 2000, 4000 Hz) were repetitively examined in early postoperative period.

Main Outcome Measures:

Subjective symptoms and pure-tone audiometry.

Results:

Transient BC threshold increase was detected in all cases in early postoperative period and hearing levels were ameliorated in 1 to 2 months. The mean maximum BC threshold elevations (dB) during the early postoperative period (within 1 mo) and the postoperative stable hearing period (after 2 mo) were 18.6 and 2.9 at 250 Hz, 24.3 and 8.6 at 500 Hz, 26.4 and 8.6 at 1000 Hz, 28.6 and 7.1 at 2000 Hz, and 30.0 and 0.8 (except for scale-out cases) at 4000 Hz. respectively. The mean maximum BC thresholds in the early period were significantly elevated compared with those in the stable period at each frequency (p < 0.01).

Conclusions:

Hearing outcomes of transmastoid plugging with transection of the membranous superior canal by using UWEES were found favorable in a long-term follow-up. However, it caused transient reversible hearing loss in all cases. The BC increase in early postoperative period may not cause permanent hearing loss but improvement for the surgical technique may still be necessary.
Inpatient Alcohol Cessation Counseling Is Associated With a Lower 30-Day Hospital Readmission in Acute Alcoholic Pancreatitis
Authors: Sorrento Cristina , Shah Ishani , Yakah William , Ahmed Awais , Tintara Supisara , Kandasamy Cinthana , Freedman Steven D. , Kothari Darshan J. , Sheth Sunil G.
Published: January 2022

Background:

Alcohol use is a common cause of recurrent acute pancreatitis. Thus, guidelines recommend providing alcohol prevention resources during hospitalization. There is limited data on the real-world implementation of this recommendation. We aimed to assess how often inpatients admitted with alcohol-induced acute pancreatitis (AAP) receive counseling and to determine the impact of counseling on readmissions for AAP.

Methods:

We retrospectively studied patients admitted with AAP at a tertiary care center from 2008 to 2018. We compared demographics, clinical features, and outcomes in patients who did and did not receive counseling. Outcomes studied were the proportion of patients with AAP receiving counseling, and readmission rates for AAP at 30 days and 1 year.

Results:

A total of 243 patients with AAP were identified, of which 115 had inpatient alcohol counseling (47%). Demographic data were comparable between the 2 groups. Fewer patients receiving alcohol counseling were readmitted at 30 days compared with patients not receiving counseling (19.3% vs. 31.2%, P=0.048). At 1 year, the 2 groups had similar readmission rates. On multivariate analysis, patients who received counseling were half as likely to be readmitted in 30 days compared with those who did not receive counseling [odds ratio=0.52 (0.27, 0.98), P=0.046].

Conclusions:

We note that <50% of patients receive alcohol counseling. Patients receiving alcohol counseling were less likely to be readmitted at 30 days, inferring possible value in the intervention provided. Similar readmission rates at 1 year suggest that the single intervention may not have a durable effect on alcohol prevention.
Utilization of Hepatocellular Carcinoma Surveillance Programs in Patients With Cirrhosis
Authors: Ramai Daryl , Singh Jameel , Chandan Saurabh , Tartaglia Nicola , Ambrosi Antonio , Khan Shahab R. , Sacco Rodolfo , Facciorusso Antonio
Published: January 2022

Patients with cirrhosis are advised to undergo hepatocellular carcinoma (HCC) surveillance every 6 months. Routine surveillance is associated with early tumor detection and improved survival. However, surveillance is underutilized. We aimed to characterize the uptake of HCC surveillance in cirrhotic patients following the implementation of interventional programs. We performed a comprehensive literature search of major databases (from inception to October 2020). Surveillance was defined as having an abdominal sonogram every 6 months. Nine studies were included for meta-analysis which involved 4550 patients. The etiology of liver cirrhosis was largely due to hepatitis C or B (n=2023), followed by alcohol (n=857), and nonalcoholic steatohepatitis (n=432). Patients enrolled in surveillance programs were 6 times more likely to undergo abdominal sonography when compared with standard of care (odds ratio=6.00; 95% confidence interval: 3.35-10.77). On subgroup analysis, clinical reminders were associated with a 4 times higher rate of HCC surveillance compared with standard of care (odds ratio=3.80; 95% confidence interval: 2.25-6.39). Interventional programs significantly improve the rate of HCC surveillance. This is clinically impactful and should be considered as a means for improving surveillance rates.
Retrospective Assessment of Patient and Catheter Characteristics Associated With Malpositioned Central Venous Catheters in Pediatric Patients
Authors: Weber Mark D. , Conlon Thomas , Woods-Hill Charlotte , Watts Stephanie L. , Nelson Eileen , Traynor Danielle , Zhang Bingqing , Davis Daniela , Himebauch Adam S.
Published: January 2022

OBJECTIVES:

The primary objective was to determine the prevalence and characteristics associated with malpositioned temporary, nontunneled central venous catheters (CVCs) placed via the internal jugular (IJ) and subclavian (SC) veins in pediatric patients.

DESIGN:

Single-center retrospective cohort study.

SETTING:

Quaternary academic PICU.

PATIENTS:

Children greater than 1 month to less than 18 years who had a CVC placed between January 2014 and December 2018.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

The primary outcome was the CVC tip position located on the first postprocedural radiograph. CVC tip was defined as follows: “recommended” (tip location between the carina and two vertebral bodies inferior to the carina), “high” (tip location between one and four vertebral bodies superior to the carina), “low” (tip position three or more vertebral bodies inferior to the carina), and “other” (tip grossly malpositioned). Seven hundred eighty-one CVCs were included: 481 (61.6%) were in “recommended” position, 157 (20.1%) were “high,” 131 (16.8%) were “low,” and 12 (1.5%) were “other.” Multiple multinomial regression (referenced to “recommended” position) showed that left-sided catheters (adjusted odds ratio [aOR], 2.00, 95% CI 1.17-3.40) were associated with “high” CVC tip positions, whereas weight greater than or equal to 40 kg had decreased odds of having a “high” CVC tip compared with the reference (aOR, 0.45; 95% CI, 0.24–0.83). Further, weight category 20–40 kg (aOR, 2.42; 95% CI, 1.38–4.23) and females (aOR, 1.51; 95% CI, 1.01–2.26) were associated with “low” CVC tip positions. There was no difference in rates of central line–associated blood stream infection, venous thromboembolism, or tissue plasminogen activator usage or dose between the CVCs with tips outside and those within the recommended location.

CONCLUSIONS:

The prevalence of IJ and SC CVC tips outside of the recommended location was high. Left-sided catheters, patient weight, and sex were associated with malposition. Malpositioned catheters were not associated with increased harm.
Low hepatitis C virus-viremia prevalence yet continued barriers to direct-acting antiviral treatment in people living with HIV in the Netherlands
Authors: Isfordink Cas J. , Smit Colette , Boyd Anders , de Regt Marieke J.A. , Rijnders Bart J.A. , van Crevel Reinout , Ackens Robin P. , Reiss Peter , Arends Joop E. , van der Valk Marc
Published: January 2022

Objective:

To describe hepatitis C virus (HCV)-viremia prevalence and barriers to direct-acting antiviral (DAA) treatment during unrestricted access to DAA in a nationwide cohort of people with HIV (PWH).

Design:

Retrospective analysis of prospectively collected data.

Methods:

We calculated yearly HCV-viremia prevalence as proportion of HCV RNA-positive individuals ever HCV-tested. We then included HCV-viremic individuals with ≥1 visit during the era of universal DAA-access (database lock = December 31, 2018). Based on their last visit, individuals were grouped as DAA-treated or -untreated. Variables associated with lack of DAA-treatment were assessed using targeted maximum likelihood estimation. In November 2020, physicians of DAA-untreated individuals completed a questionnaire on barriers to DAA-uptake and onward HCV-transmission risk.

Results:

Among 25 196 PWH, HCV-viremia decreased from 4% to 5% between 2000 and 2014 to 0.6% in 2019. Being DAA-untreated was associated with HIV-transmission route other than men who have sex with men, older age, infrequent follow-up, severe alcohol use, detectable HIV-RNA, HCV-genotype 3, and larger hospital size. With universal DAA-access, 72 of 979 HCV-viremic individuals remained DAA-untreated at their last visit. Of these, 39 were no longer in care, 27 remained DAA-untreated in care, and six initiated DAA since database lock. Most common physician-reported barriers to DAA-uptake were patient refusal (20/72, 28%) and infrequent visit attendance (19/72, 26%). Only one DAA-untreated individual in care was engaging in activities associated with onward HCV-transmission.

Conclusions:

Prevalence of HCV-viremic PWH is low in the Netherlands, coinciding with widespread DAA-uptake. Barriers to DAA-uptake appear mostly patient-related, while HCV-transmission seems unlikely from the few DAA-untreated in care.
Diabetes mellitus is associated with declines in physical function among men with and without HIV
Authors: Masters Mary C. , Yang Jingyan , Lake Jordan E. , Abraham Alison G. , Kingsley Lawrence , Brown Todd T. , Palella Frank J. , Erlandson Kristine M.
Published: January 2022

Objective:

To determine the longitudinal relationships between abnormal glucose metabolism and physical function in persons with HIV (PWH) and without HIV.

Design:

Prospective cohort study of men with or at risk for HIV in four United States cities between 2006 and 2018.

Methods:

Men with or at risk for HIV from the Multicenter AIDS Cohort Study (MACS) had semi-annual assessments of glycemic status, grip strength, and gait speed. We used linear mixed models with random intercept to assess associations between glycemic status and physical function. Glycemic status was categorized as normal, impaired fasting glucose (IFG), controlled diabetes mellitus [hemoglobin A1C (HbA1C) <7.5%], or uncontrolled diabetes mellitus (HbA1C ≥ 7.5%).

Results:

Of 2240 men, 52% were PWH. Diabetes mellitus was similar among PWH (7.7%) vs. persons without HIV (6.7%, P = 0.36) at baseline. PWH had slower gait speed (1.17 vs. 1.20 m/s, P < 0.01) but similar grip strength (40.1 vs. 39.8 kg, P = 0.76) compared with persons without HIV at baseline. In multivariate models, gait speed decline was greater with controlled diabetes mellitus [−0.018 m/s (−0.032 to −0.005), P = 0.01] and grip strength decline was greater with controlled [−0.560 kg (−1.096 to −0.024), P = 0.04] and uncontrolled diabetes mellitus [−0.937 kg (−1.684 to −0.190), P = 0.01), regardless of HIV serostatus compared with normoglycemic individuals.

Discussion:

Abnormal glucose metabolism was associated with declines in gait speed and grip strength regardless of HIV serostatus. These data suggest that improvement in glucose control should be investigated as an intervenable target to prevent progression of physical function limitations among PWH.
Safety and Immunogenicity of SARS-CoV-2 vaccines in people with HIV
Authors: González de Aledo Manuel , Cañizares Angelina , Vázquez-Rodríguez Pilar , Castro Ángeles , Moldes Luz , López Soledad , Míguez Enrique , Bou Germán , Mena Álvaro
Published: January 2022

Objective:

To evaluate the safety and the serological response after two doses of mRNA-based SARS-CoV-2 vaccination in people with HIV (PWH).

Methods:

Participants were evaluated 4 weeks after the second dose of mRNA-1273 or BNT162b2 vaccine. Tolerability was evaluated with a specific adverse event questionnaire. Patient's sera were analysed using LIAISON SARS-CoV-2 TrimericS IgG (DiaSorin).

Results:

One-hundred PWH were included, 75% of them men, with a mean age of 44 ± 11 years old, all receiving antiretroviral treatment and mostly with controlled viral loads (98% with HIV RNA <50 copies/ml) and 96% had >200 CD4+/μl. All patients seroconverted after vaccination (antibody concentration ≥33.8 binding antibody units [BAU]/ml). Only 3% of the patients had a low antibody concentration (<520 BAU/ml), whereas 67% of them had concentrations above the assay's detection range (>2080 BAU/ml). Fifty-six patients had local or systemic symptoms, with mild arthromyalgia being the most common systemic symptom. No severe adverse events were reported.

Conclusions:

Vaccination with two doses of mRNA-1273 or BNT162b2 is well tolerated in PWH under effective antiretroviral treatment and it leads to a successful antibody response.
Impact of Deep Learning Reconstruction Combined With a Sharpening Filter on Single-Shot Fast Spin-Echo T2-Weighted Magnetic Resonance Imaging of the Uterus
Authors: Tsuboyama Takahiro , Onishi Hiromitsu , Nakamoto Atsushi , Ogawa Kazuya , Koyama Yoshihiro , Tarewaki Hiroyuki , Tomiyama Noriyuki
Published: January 2022

Objective

This study aimed to evaluate the effects of deep learning (DL) reconstruction and a postprocessing sharpening filter on the image quality of single-shot fast spin-echo (SSFSE) T2-weighted imaging (T2WI) of the uterus.

Materials and Methods

Fifty consecutive patients who underwent pelvic magnetic resonance imaging were included. Parasagittal T2WI with a slice thickness of 4 mm was obtained with the periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) and SSFSE sequences (mean scan time, 204 and 22 seconds, respectively). The following 3 types of SSFSE images were reconstructed, and the signal-to-noise ratio (SNR) and tissue contrast were assessed: conventional reconstruction (SSFSE-C), DL reconstruction (SSFSE-DL), and DL with a sharpening filter (SSFSE-DLF). Three radiologists independently assessed image quality, and area under the visual grading characteristics curve (AUCVGC) analysis was performed to compare the SSFSE and PROPELLER images.

Results

Compared with that of the PROPELLER images, the SNR of the SSFSE-C, SSFSE-DL, and SSFSE-DLF images was significantly lower (P < 0.05), significantly higher (P < 0.05), and equivalent, respectively. The SSFSE-DL images exhibited significantly lower contrast between the junctional zone and myometrium than those obtained with the other sequences (P < 0.05). In qualitative comparisons with the PROPELLER images, all 3 SSFSE sequences, SSFSE-DL, and SSFSE-DLF demonstrated significantly higher scores for artifacts, noise, and sharpness, respectively (P < 0.01). The overall image quality of SSFSE-C (mean AUCVGC, 0.03; P < 0.01) and SSFSE-DL (mean AUCVGC, 0.23; P < 0.01) was rated as significantly inferior, whereas that of SSFSE-DLF (mean AUCVGC, 0.69) was equivalent or significantly higher (P < 0.01).

Conclusion

Using a combination of DL and a sharpening filter markedly increases the image quality of SSFSE of the uterus to the level of the PROPELLER sequence.
Comparison of the Surgical Outcomes of Cranioplasty Using Titanium, Customized Polymethylmethacrylate, and Liquid Polymethylmethacrylate in Maharaj Nakhon Chiang Mai Hospital, Thailand
Authors: Vongsfak Jirapong , Vaniyapong Tanat , Norasethada Thunya , Watcharasaksilp Wanarak , Jetjumnong Chumpon , Srihagulang Chanon , Limpastan Kriengsak
Published: January 2022

Cranioplasty is a standard procedure used to restore skull defects after craniectomy. Many different materials are used in cranioplasty. The study aim was to compare the surgical outcomes of cranioplasty using different materials: liquid polymethylmethacrylate (PMMA), customized PMMA, and titanium. The authors retrospectively reviewed the outcomes of cranioplasty performed from 2016 to 2021. Data collection included patient characteristics and complications, including postoperative infection, hematoma, implant exposure, and subgaleal cerebrospinal fluid collection. Eighty-five patients received cranioplasty with different materials: titanium, 14; customized PMMA, 31; and liquid PMMA, 40. There were no significant differences in the basic patient characteristics among the 3 cranioplasty groups except for lower age in the customized PMMA group. There were no significant differences between superficial and deep infections, implant exposure, postoperative hematoma, or seizure. However, subgaleal cerebrospinal fluid collection was more common in the liquid PMMA group than in the customized PMMA group (P = 0.02). This study showed that good outcomes were achieved by cranioplasty performed with different materials (titanium, customized PMMA, and liquid PMMA).
Nonmydriatic Retinal Photography in the Outpatient Neurology Resident Clinic
Authors: Pyatka Nataliya , Banks Matthew K. , Fotedar Neel , DeLozier Sarah J. , Morgan Michael , Preston David C.
Published: January 2022

Background:

The funduscopic examination is an essential component of the neurologic examination. However, examination of the ocular fundus with a direct ophthalmoscope is often difficult. Nonmydriatic ocular fundus photography allows direct visualization of the ocular fundus with high-quality photographs. We used nonmydriatic ocular fundus photography to improve patient care and funduscopy skills of residents in the Neurology Resident Clinic.

Methods:

At the time of triage, funduscopic photographs of all new neurology resident clinic patients were taken. The images were imported into the hospital's imaging software. The residents completed a full neurologic examination, including a funduscopic examination with a handheld ophthalmoscope. At the time of staffing the patients with the attendings, the residents received immediate feedback and teaching on retina photograph evaluation.

Results:

A total of 255 patients were enrolled. Of those, 230 (90%) had at least one high-quality funduscopic photograph. Retinal photographs were normal in 161 (70%). Out of the 69 abnormal photographs, only 7% of abnormalities were detected by the residents. Ninety-three percent of residents found the retinal photographs useful.

Conclusions:

Nonmydriatic ocular fundus photography improved the care in patients presenting to a Neurology resident clinic and facilitated residents in recognizing funduscopic findings. Its benefits are clear when one considers (1) the high risk of negative patient outcomes and possible medicolegal consequences due to missed findings, (2) the ease of incorporating retinal photographs into the patients' medical records, and (3) the benefit of improving resident education in regard to the ophthalmologic examination.
Orbital Inflammation in Myelin Oligodendrocyte Glycoprotein Antibody–Associated Disease: A Case Report and Review of the Literature
Authors: Liou Victor D. , Yoon Michael K. , Maher Mary , Chwalisz Bart K.
Published: January 2022

Background:

To present 2 patients with myelin oligodendrocyte glycoprotein (MOG) antibody–associated disease with unilateral orbital inflammation, optic nerve head edema, and abnormalities of the optic nerve and nerve sheath on imaging. We review the most current literature on this important and uncommon clinical phenotype.

Methods:

A case report of 2 patients and a comprehensive review of the relevant literature on orbital inflammation in MOG antibody–associated disease (MOG-AD).

Results:

Two patients presented with decreased vision and unilateral orbital inflammation. Both had optic nerve head edema and abnormalities of the optic nerve and nerve sheath on imaging. The patients were treated with immunosuppressants and had improvement of vision changes as well as their orbital inflammatory signs. MOG antibody was positive in high titers in both patients. Only 3 other cases of orbital inflammation associated with MOG antibody have been described. In all cases, orbital signs responded rapidly to intravenous methylprednisolone, but the improvement in visual acuity was variable and less robust.

Conclusion:

Orbital inflammation is a unique and underrecognized phenotype of MOG-AD with only a few reports in the literature. In patients who present with vision loss and orbital inflammation, MOG-AD should be considered in the differential.
Multidomain Cognitive Impairment in Children With Pseudotumor Cerebri Syndrome
Authors: Mahajnah Muhammad , Suchi Ariel T. , Zahakah Hazar , Sharkia Rajech , Shuhaiber Shaden R. , Srugo Isaac , Genizi Jacob
Published: January 2022

Background:

Although prompt and suitable treatment of pseudotumor cerebri syndrome (PTCS) leads to an excellent prognosis and can prevent optic nerve atrophy, adults show long-lasting neurocognitive deficits even with prompt treatment. The purpose of our study was to evaluate cognitive outcomes in pediatric patients with PTCS.

Methods:

We performed a prospective study on children diagnosed with PTCS and a healthy control group. Children with pre-existing neurological conditions or psychiatric drug use were excluded. Both groups underwent a neurocognitive evaluation, using the NeuroTrax computerized battery of tests. The PTCS group were tested 3 months after the initial diagnosis.

Results:

We evaluated 82 children (49 females [60%], 6.5–16 years old, mean age 13.3), including 26 diagnosed with idiopathic PTC and 56 controls. Global cognitive score (P < 0.001), verbal memory (P < 0.001), executive function (P < 0.001), attention (P< 0.003), and information processing speed (P < 0.004) were all significantly lower in the PTCS group. No differences were found between children currently being treated and those whose symptoms had resolved and treatment was stopped.

Conclusions:

Children with PTCS experience comprehensive cognitive decline that persists after the resolution of the symptoms and treatment.
Clinical Neurophysiology of Zika Virus Encephalitis
Authors: Ferrari-Marinho Taissa , De Marchi Luciana R. , Caboclo Luis Otavio
Published: January 2022

Zika virus (ZIKV) has been shown to be highly neurotropic; neurologic disorders are a common complication of this infection. Encephalitis—an inflammation of the brain parenchyma associated with neurologic dysfunction—is a rare complication of ZIKV infections. It affects patients from young to elderly ages. Clinical presentation of ZIKV encephalitis may be heterogeneous, including altered mental status (decreased or altered level of consciousness, lethargy, or personality change), seizures, and focal deficits. Complementary diagnostic investigation should include neuroimaging, lumbar puncture, and EEG. Neuroimaging findings in ZIKV encephalitis are not specific and may be diverse, including normal findings, hyperintense lesions on MRI involving cortical or subcortical structures, symmetric or asymmetric lesions involving supra or infratentorial regions, and more widespread involvement such as brain swelling. A remarkable scarcity of neurophysiological data on ZIKV encephalitis was found in the literature. In line with other diagnostic examinations, there are no neurophysiological findings suggestive or specific of the disease. EEG in ZIKV encephalitis showed different results: normal or diffuse disorganization of background activity, asymmetry with abnormal focal slow waves, focal epileptic discharges or generalized spike–wave and multispike–wave complexes, and periods of generalized voltage attenuation.
Does the morphology of the posterior malleolar fragment influence clinical outcomes of trimalleolar fractures after surgical fixation? A systematic review and Meta-analysis
Authors: Patel Sandeep , Dhillon Mandeep Singh , Baburaj Vishnu , Sharma Siddhartha
Published: January 2022

Background

Posterior malleolus (PM) fractures have historically been classified according to the size of the fragment, to study the need for surgical fixation and to assess clinical outcomes. Recent research has suggested that the morphology of the PM fragment is of more relevance than its size.

Objectives

This systematic review aims to determine if the size of the PM fragment influences clinical outcomes of trimalleolar fractures after surgical fixation, and if so, to find out which fracture type has the best outcomes.

Methods

This systematic review will be conducted according to the PRISMA guidelines. A literature search will be conducted on the electronic databases of PubMed, Embase, Scopus and Ovid with a pre-determined search strategy. A manual bibliography search of included studies will also be done. Original articles in English that have relevant data on the outcomes of PM fractures and its morphology will be included. Data will be extracted from included studies and analysis carried out with the help of appropriate software.
Extracting abundance information from DNA-based data
Authors: Luo Mingjie , Ji Yinqiu , Warton David , Yu Douglas W.
Published: January 2022

The accurate extraction of species-abundance information from DNA-based data (metabarcoding, metagenomics) could contribute usefully to diet analysis and food-web reconstruction, the inference of species interactions, the modelling of population dynamics and species distributions, the biomonitoring of environmental state and change, and the inference of false positives and negatives. However, multiple sources of bias and noise in sampling and processing combine to inject error into DNA-based datasets. We focus here on the laboratory and bioinformatic processes of generating DNA-based data, since sampling bias and noise are addressed extensively in the ecological literature. To extract abundance information, it is useful to distinguish two concepts. (1)Within-sample across-speciesquantification describes relative species abundances within one sample. (2)Across-sample within-speciesquantification describes how the abundance of each individual species varies from sample to sample, as in a time series, an environmental gradient, or experimental treatments. First, we review the literature on methods to recover (1)across-speciesabundance information (which is achieved by removing what we call ‘species pipeline biases’) and (2)within-speciesabundance information (by removing what we call ‘pipeline noise’). We argue that many ecological questions can be answered by extracting only within-species quantification, and we therefore demonstrate how to use a ‘DNA spike-in’ to correct for pipeline noise and recover within-speciesabundance information. We also introduce a model-based estimator that can be employed on datasets without a physical spike-in to approximately estimate and correct for pipeline noise.
Multi-micron crisscross structures from combinatorially assembled DNA-origami slats
Authors: Wintersinger Christopher M. , Minev Dionis , Ershova Anastasia , Sasaki Hiroshi M. , Gowri Gokul , Berengut Jonathan F. , Corea-Dilbert F. Eduardo , Yin Peng , Shih William M.
Published: January 2022

Living systems achieve robust self-assembly across length scales. Meanwhile, nanofabrication strategies such as DNA origami have enabled robust self-assembly of submicron-scale shapes.However, erroneous and missing linkages restrict the number of unique origami that can be practically combined into a single supershape. We introduce crisscross polymerization of DNA-origami slats for strictly seed-dependent growth of custom multi-micron shapes with user-defined nanoscale surface patterning. Using a library of ~2000 strands that can be combinatorially assembled to yield any of ~1e48 distinct DNA origami slats, we realize five-gigadalton structures composed of >1000 uniquely addressable slats, and periodic structures incorporating >10,000 slats. Thus crisscross growth provides a generalizable route for prototyping and scalable production of devices integrating thousands of unique components that each are sophisticated and molecularly precise.

One-sentence summary

Crisscross polymerization of DNA-origami slats can yield micron-scale structures with uniquely addressable nanoscale features.
Autoantibody and hormone activation of the thyrotropin G protein-coupled receptor
Authors: Faust Bryan , Singh Isha , Zhang Kaihua , Hoppe Nicholas , Pinto Antonio F. M. , Muftuoglu Yagmur , Billesbølle Christian B. , Saghatelian Alan , Cheng Yifan , Manglik Aashish
Published: January 2022

Thyroid hormones are vital to growth and metabolism. Thyroid hormone synthesis is controlled by thyrotropin (TSH), which acts at the thyrotropin receptor (TSHR). Autoantibodies that activate the TSHR pathologically increase thyroid hormones in Graves’ disease. How autoantibodies mimic TSH function remains unclear. We determined cryogenic-electron microscopy structures of active and inactive TSHR. In inactive TSHR, the extracellular domain lies close to the membrane bilayer. TSH selects an upright conformation of the extracellular domain due to steric clashes between a conserved hormone glycan and the membrane bilayer. An activating autoantibody selects a similar upright conformation of the extracellular domain. Conformational changes in the extracellular domain are transduced to the seven transmembrane domain via a conserved hinge domain, a tethered peptide agonist, and a phospholipid that binds within the seven transmembrane domain. Rotation of the TSHR ECD relative to the membrane bilayer is sufficient for receptor activation, revealing a shared mechanism for other glycoprotein hormone receptors that may also extend to G protein-coupled receptors with large extracellular domains.
Engineering SARS-CoV-2 neutralizing antibodies for increased potency and reduced viral escape
Authors: Zhao Fangzhu , Keating Celina , Ozorowski Gabriel , Shaabani Namir , Francino-Urdaniz Irene M. , Barman Shawn , Limbo Oliver , Burns Alison , Zhou Panpan , Ricciardi Michael J. , Woehl Jordan , Tran Quoc , Turner Hannah L. , Peng Linghang , Huang Deli , Nemazee David , Andrabi Raiees , Sok Devin , Teijaro John R. , Whitehead Timothy A. , Ward Andrew B. , Burton Dennis R. , Jardine Joseph G.
Published: January 2022

The rapid spread of SARS-CoV-2 variants poses a constant threat of escape from monoclonal antibody and vaccine countermeasures. Mutations in the ACE2 receptor binding site on the surface S protein have been shown to disrupt antibody binding and prevent viral neutralization. Here, we use a directed evolution-based approach to engineer three neutralizing antibodies for enhanced binding to S protein. The engineered antibodies showed increased in vitro functional activity in terms of neutralization potency and/or breadth of neutralization against viral variants. Deep mutational scanning revealed that higher binding affinity reduced the total number of viral escape mutations. Studies in the Syrian hamster model showed two examples where the affinity matured antibody provided superior protection compared to the parental antibody. These data suggest that monoclonal antibodies for anti-viral indications could benefit from in vitro affinity maturation to reduce viral escape pathways and appropriate affinity maturation in vaccine immunization could help resist viral variation.
The role of metal binding in the function of the human salivary antimicrobial peptide histatin-5
Authors: Stewart Louisa , Hong YoungJin , Holmes Isabel , Firth Samantha , Bolton Jack , Santos Yazmin , Cobb Steven , Jakubovics Nicholas , Djoko Karrera
Published: January 2022

Antimicrobial peptides (AMPs) are key components of diverse host innate immune systems. The family of human salivary AMPs known as histatins bind Zn and Cu. Fluctuations in Zn and Cu availability play significant roles in the host innate immune response (so-called “nutritional immunity”). Thus, we hypothesised that histatins contribute to nutritional immunity by influencing host Zn and/or Cu availability. We posited that histatins limit Zn availability (promote bacterial Zn starvation) and/or raise Cu availability (promote bacterial Cu poisoning). To test this hypothesis, we examined the interactions between histatin-5 (Hst5) and Group A Streptococcus (GAS), which colonises the human oropharynx. Our results showed that Hst5 does not strongly influence Zn availability. Hst5 did not induce expression of Zn-responsive genes in GAS, nor did it suppress growth of mutant strains that are impaired in Zn transport. Biochemical examination of purified peptides confirmed that Hst5 binds Zn only weakly. By contrast, Hst5 bound Cu tightly and it strongly influenced Cu availability. However, Hst5 did not promote Cu toxicity. Instead, Hst5 suppressed expression of Cu-inducible genes, stopped intracellular accumulation of Cu, and rescued growth of a ΔcopA mutant strain that is impaired in Cu efflux. We thus proposed a new role for salivary histatins as major Cu buffers in saliva that contribute to microbial homeostasis in the oral cavity and oropharynx by reducing the potential negative effects of Cu exposure (e.g. from food) to microbes. Our results raise broad questions regarding the physiological roles of diverse metal-binding AMPs and the management of host metal availability during host-microbe interactions.
Covariant Fitness Clusters Reveal Structural Evolution of SARS-CoV-2 Polymerase Across the Human Population
Authors: Wang Chao , Elghobashi-Meinhardt Nadia , Balch William E.
Published: January 2022

Understanding the fitness landscape of viral mutations is crucial for uncovering the evolutionary mechanisms contributing to pandemic behavior. Here, we apply a Gaussian process regression (GPR) based machine learning approach that generates spatial covariance (SCV) relationships to construct stability fitness landscapes for the RNA-dependent RNA polymerase (RdRp) of SARS- CoV-2. GPR generated fitness scores capture on a residue-by-residue basis a covariant fitness cluster centered at the C487-H642-C645-C646 Zn2+binding motif that iteratively evolves since the early phase pandemic. In the Alpha and Delta variant of concern (VOC), multi-residue SCV interactions in the NiRAN domain form a second fitness cluster contributing to spread. Strikingly, a novel third fitness cluster harboring a Delta VOC basal mutation G671S augments RdRp structural plasticity to potentially promote rapid spread through viral load. GPR principled SCV provides a generalizable tool to mechanistically understand evolution of viral genomes at atomic resolution contributing to fitness at the pathogen-host interface.
Common neural functions during children’s naturalistic and controlled laboratory mathematics learning
Authors: Amalric Marie , Cantlon Jessica F
Published: January 2022

A major goal of human neuroscience is to understand how the brain functions in the real world, and to measure neural processes under conditions that are ecologically valid. A critical step toward this goal is understanding how brain activity during naturalistic tasks that mimic the real world, relates to brain activity in more traditional laboratory tasks. In the present study, we used intersubject correlations to locate reliable stimulus-driven cerebral processes among children and adults in a naturalistic video lesson and a laboratory forced-choice task that shared the same arithmetic concept. We show that relative to a control condition with grammatical content, naturalistic and laboratory arithmetic tasks evoked overlapping activation within brain regions previously associated with math semantics. The regions of specific functional overlap between the naturalistic mathematics lesson and laboratory mathematics task included bilateral intraparietal cortex, which confirms that this region processes mathematical content independently of differences in task mode. These findings suggest that regions of the intraparietal cortex process mathematical content when children are learning about mathematics in the real world.