bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Algorithm for Defining the Mandibular Border
Authors: Rohrich Rod J. , Agrawal Nikhil A. , Avashia Yash , Savetsky Ira L.
Published: February 2022

Techniques for defining the mandibular angle are a particular focus for patients around the world. Developing the desirable sharp contours is a combination of reducing bulkiness around the mandible while augmenting the border. Invasive techniques (e.g., face lifts and chin augmentation) can help define the mandible; however, younger patients are demanding more affordable and less invasive procedures. The “Nefertiti lift,” masseter neurotoxin, buccal fat excision, mandibular border augmentation with filler, and liposuction of the neck can all be done in the office and will produce excellent results. If the loss of definition is due to superior soft tissue, the next step is to determine if this is based on anterior or posterior soft-tissue excess. Posteriorly, it is caused by masseter hypertrophy, and anteriorly, it may be because of an enlarged or full buccal fat pad in the lower cheek area. If the loss of definition is inferior, the next step is to again define if it is anterior or posterior. Anterior excess tissue can be corrected with liposuction of the neck along with energy-based skin tightening technology. Posteriorly, the inferior pull of the platysma can be blunted with neurotoxin. Finally, once the soft tissues are adequate, the mandibular border can be augmented with filler. In this article, the authors propose an algorithm for when to utilize each of these procedures while reviewing proper technique.
Safety and Efficacy of Local Tranexamic Acid for the Prevention of Surgical Bleeding in Soft-Tissue Surgery: A Review of the Literature and Recommendations for Plastic Surgery
Authors: Ausen Kjersti , Fossmark Reidar , Spigset Olav , Pleym Hilde
Published: February 2022

Background:

Although high-bleed surgery routinely utilizes the antifibrinolytic drug tranexamic acid, most plastic surgical procedures are conducted in soft tissue with low-volume bleeding. Unease regarding possible systemic adverse effects prevents widespread systemic use, but local use of tranexamic acid is gaining popularity among plastic surgeons. Randomized controlled trials on topical use of tranexamic acid are mainly from high-bleed surgeries, and few studies address the effect in soft tissue. This article reviews the scientific evidence regarding local use of tranexamic acid in soft-tissue surgery, discusses pharmacological effects and possible adverse reactions, and presents recommendations for use in plastic surgery.

Methods:

A systematic search of databases for studies on local use of tranexamic acid in soft-tissue surgery was performed. Randomized controlled trials were included for a systematic review on effect; a narrative review regarding other clinically relevant aspects is based on extensive literature searches combined with the authors’ own research.

Results:

Fourteen randomized controlled trials, including 1923 patients, were included in the systematic review on local use of tranexamic acid in soft-tissue surgery.

Conclusions:

Local use of tranexamic acid may reduce blood loss comparably to intravenous prophylactic use with negligible risk of systemic adverse effects, but high-quality randomized controlled trials are few. Prolonged exposure to high local concentrations is discouraged, and direct contact with the central nervous system may cause seizures. No single superior means of administration or dosage is supported in the literature, and lowest effective dose is unknown. There may not be one single ideal dosing regimen, but rather many possibilities adaptable for different surgical situations.
How Do You Like Me Now? The Influence of “Likes” and Followers on Social Media in Plastic Surgery
Authors: Bhat Deepa , Kollu Tejas , Ricci Joseph A. , Patel Ashit
Published: February 2022

Background:

The number of “likes” and followers on social media is a surrogate marker for peer acceptance and popularity, but the influence of likes and followers on prospective plastic surgery patients has not been studied. The aim of this study was to evaluate whether the number of followers or likes on social media has an impact on perceived surgeon competence or likelihood of recruiting new patients.

Methods:

A fictitious Instagram page was created with different permutations displaying different numbers of followers on the page. Similarly, fictitious Instagram posts were created displaying before-and-after results of ideal and suboptimal breast augmentation and gynecomastia surgery results, with the number of likes being the only variable. Using a crowdsourcing platform, survey responders rated surgeon competence and likelihood of patient recruitment based on the Instagram post.

Results:

A total of 4284 responses were collected. The number of followers or likes did not impact perceived surgeon competence or patient recruitment scores. Optimal surgical results consistently scored higher than suboptimal results, regardless of the number of likes. Almost half the responders were unable to identify the American Board of Plastic Surgery as the appropriate board certification for performing aesthetic breast or body surgery.

Conclusions:

A high number of followers or likes, by itself, is unlikely to translate into higher likelihood of recruiting new patients. Overall, aesthetic results seem to be the most important driving force in receiving high competence scores and recruiting new patients, rather than social media presence or board certification.
Use of Diagnosis Codes to Find Blood Transfusion Adverse Events in Electronic Health Records
Authors: Bright Roselie A. , Bright-Ponte Susan J. , Palmer Lee Anne M. , Rankin Summer K. , Blok Sergey V.
Published: February 2022

Objective

Electronic health records (EHRs) and big data tools offer the opportunity for surveillance of adverse events (patient harm associated with medical care). We used International Classification of Diseases, Ninth Revision, codes in electronic records to identify known, and potentially novel, adverse reactions to blood transfusion.

Methods

We used 49,331 adult admissions involving critical care at a major teaching hospital, 2001–2012, in the Medical Information Mart for Intensive Care III EHRs database. We formed a T (defined as packed red blood cells, platelets, or plasma) group of 21,443 admissions versus 25,468 comparison (C) admissions. The International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis codes were compared for T versus C, described, and tested with statistical tools.

Results

Transfusion adverse events (TAEs) such as transfusion-associated circulatory overload (TACO; 12 T cases; rate ratio [RR], 15.61; 95% confidence interval [CI], 2.49–98) were found. There were also potential TAEs similar to TAEs, such as fluid overload disorder (361 T admissions; RR, 2.24; 95% CI, 1.88–2.65), similar to TACO. Some diagnoses could have been sequelae of TAEs, including nontraumatic compartment syndrome of abdomen (52 T cases; RR, 6.76; 95% CI, 3.40–14.9) possibly being a consequence of TACO.

Conclusions

Surveillance for diagnosis codes that could be TAE sequelae or unrecognized TAE might be useful supplements to existing medical product adverse event programs.
Increased Genioglossus Muscle FDG Activity Due to Using Pacifier
Authors: Tong Celia , Zhuang Hongming
Published: February 2022

An 18-month-old girl with history of liver transplant underwent FDG PET/CT to evaluate posttransplant lymphoproliferative disorder. In addition to multistation hypermetabolic lymphadenopathy and abnormal activity in the liver, stomach, and small bowel, in keeping with known posttransplant lymphoproliferative disorder, the images also showed focal activity in the submental region. This submental activity persisted on 2 separate follow-up FDG PET/CT studies, even though other foci of abnormal activity resolved after chemotherapy. Records revealed that the patient was sucking on a pacifier prior to all 3 FDG PET/CT studies, and the submental uptake corresponded with genioglossus muscle activity.
18F-FDG PET/CT Findings in HIV-Positive Patient With Primary Pancreas Lymphoma and CMV Pancreatitis
Authors: Beyhan Ediz , Erol Fenercioğlu Özge , Şahin Rahime , Baloğlu Mehmet Can , Çermik Tevfik Fikret
Published: February 2022

A 35-year-old HIV-positive man with abdominal pain was referred to 18F-FDG PET/CT for metabolic characterization of mass in pancreas. PET/CT images showed intense FDG uptake in head of the pancreas, as well as diffuse moderate uptake throughout body and tail of the pancreas. Histopathological results revealed Epstein-Barr virus (EBV) associated large B-cell lymphoma and pancreatitis caused by cytomegalovirus.
Incidental Detection of Viral Conjunctivitis on 68Ga-DOTANOC PET/CT in a Patient Suspected With Von Hippel–Lindau Syndrome
Authors: Mathur Yamini , Krishnaraju Venkata Subramanian , Singh Harmandeep , Kumar Rajender , Dutta Pinaki
Published: February 2022

Von Hippel–Lindau syndrome is an autosomal dominant disorder. It is associated with a spectrum of benign and malignant tumors, including pancreatic and adrenal neuroendocrine tumors, renal cell carcinoma, and hemangioblastomas of the central nervous system and retina. 68Ga-DOTANOC PET/CT has shown somatostatin receptor expression in inflammatory conditions. In the present case, we report that 68Ga-DOTANOC PET/CT demonstrates the tracer avidity in the bilateral swollen eyelids in a patient with clinical suspicion of Von Hippel–Lindau syndrome, which was confirmed as viral conjunctivitis on clinical examination.
The Kampala Trauma Score: A 20-year track record
Authors: Rosenkrantz Leah , Schuurman Nadine , Hameed Morad S. , Boniface Respicious , Lett Ronald
Published: February 2022

Quantifying the severity of traumatic injury has been foundational for the standardization of outcomes, quality improvement research, and health policy throughout the evolution of trauma care systems. Many injury severity scores are difficult to calculate and implement, especially in low- and middle-income countries (LMICs) where human resources are limited. The Kampala Trauma Score (KTS)—a simplification of the Trauma Injury Severity Score—was developed in 2000 to accommodate these settings. Since its development, numerous instances of KTS use have been documented, but extent of adoption is unknown. More importantly, does the KTS remain useful for determining injury severity in LMICs? This review aims to better understand the legacy of the KTS and assess its strengths and weaknesses. Three databases were searched to identify scientific papers concerning the KTS. Google Scholar was searched to identify grey literature. The search returned 357 papers, of which 199 met inclusion criteria. Eighty-five studies spanning 16 countries used the KTS in clinical settings. Thirty-seven studies validated the KTS, assessing its ability to predict outcomes such as mortality or need for admission. Over 80% of these studies reported the KTS equalled or exceeded more complicated scores at predicting mortality. The KTS has stood the test of time, proving itself over the last twenty years as an effective measure of injury severity across numerous contexts. We recommend the KTS as a means of strengthening trauma systems in LMICs and suggest it could benefit high-income trauma systems that do not measure injury severity.
Appendectomy versus nonoperative management of simple appendicitis: A post hoc analysis of an Eastern Association for the Surgery of Trauma multicenter study using a hierarchical ordinal scale
Authors: Yeh D. Dante , Vasileiou Georgia , Qian Sinong , Zhang Hang , Abdul Jawad Khaled , Dodgion Chris , Lawless Ryan , Rattan Rishi , Pust G. Daniel , Namias Nicholas
Published: February 2022

BACKGROUND

Controversy exists about the preferred initial treatment of appendicitis. We sought to compare the two treatments for initial management of simple appendicitis.

METHODS

In this post hoc analysis of the Multicenter Study for the Treatment of Appendicitis in America: Acute, Perforated, and Gangrenous database, subjects were divided into appendectomy or nonoperative management (NOM; antibiotics only or percutaneous drainage) cohorts. A novel topic-specific hierarchical ordinal scale was created with eight mutually exclusive categories: mortality, reoperation, other secondary interventions, readmission, emergency department visit, wound complication, surgical site infection, and no complication. Pairwise comparisons of American Association for the Surgery of Trauma Imaging Severity Grade 1 (simple appendicitis) patients were compared using win-lose-tie scoring and the sums of appendectomy/NOM groups were compared.

RESULTS

A total 3,591 subjects were included: 3,262 appendectomy and 329 NOM, with significant differences in baseline characteristics between groups. Across 28 sites, the rate of NOM ranged from 0% to 48%, and the loss to follow-up rate was significantly higher for NOM compared with appendectomy (16.5% vs. 8.7%, p = 0.024). In the simple appendicitis hierarchical ordinal scale analysis, 2,319 subjects resulted in 8,714,304 pairwise comparisons; 75% of comparisons resulted in ties. The median (interquartile range) sums for the two groups are as follows: surgical, 400 (400–400), and NOM, 400 (−2,427 to 400) (p < 0.001). A larger proportion of appendectomy subjects (88.1%) had an outcome that was equivalent (or better) than at least half of the subjects compared with NOM subjects (NOM, 70.5%; OR [95% confidence interval], 0.3 [0.2–0.4]).

CONCLUSION

In contemporary American practice, appendectomy (compared with NOM) for simple appendicitis is associated with lower odds of developing clinically important unfavorable outcomes in the first year after illness.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Prognostic Value of the Neurological Pupil Index in Patients With Acute Subarachnoid Hemorrhage
Authors: Sharma Rahul A. , Garza Philip S. , Biousse Valérie , Samuels Owen B. , Newman Nancy J. , Bruce Beau B.
Published: February 2022

Background:

The Neurological Pupil index (NPi) provides a quantitative assessment of pupil reactivity and may have prognostic value in patients with subarachnoid hemorrhage (SAH). We aimed to explore associations between the NPi and clinical outcomes in patients with SAH.

Methods:

A retrospective analysis of 79 consecutive patients with acute SAH. Age, sex, Acute Physiology and Chronic Health Evaluation-II score, and respiratory failure and NPi in each eye were recorded at admission. The primary outcomes included death and poor clinical outcome (defined as inpatient death, care withdrawal, or discharge Glasgow Outcome Score <4). Groups were compared using the Fisher exact test, and predictive models developed with fast-and-frugal trees (FFTs).

Results:

A total of 53 patients were included: 21 (40%) had poor clinical outcomes and 2 (4%) died. Univariate analysis found that only APACHE-II score (P < 0.001) and respiratory failure (P = 0.04) were significantly associated with poor clinical outcomes. NPi was lower among patients with poor clinical outcomes (mean 4.3 in the right eye and 4.2 in the left eye) vs those without (mean 4.5 in the right eye and 4.5 in the left eye), but neither was significant. However, the most accurate FFTs for death and poor clinical outcome included NPi after accounting for age in the death FFT and APACHE-II score in the poor outcome FFT (sensitivity [sn] = 100%, specificity [sp] = 94%, and accuracy (ac) = 94% in a model for death; sn = 100%, sp = 50%, and ac = 70%) in a model for poor clinical outcome.

Conclusions:

Our study supports the NPi as a useful prognostic marker for poor outcomes in acute SAH after accounting for age and APACHE-II score.
The panniculus carnosus muscle: a missing link in the chronicity of heel pressure ulcers?
Authors: Nasir N. Jannah M. , Corrias Alberto , Heemskerk Hans , Ang Eng Tat , Jenkins Julia H. , Sebastin S. J. , Tucker-Kellogg Lisa
Published: February 2022

Chronic and recurring pressure ulcers (PUs) create an unmet need for predictive biomarkers. In this work, we examine the panniculus carnosus, a thin cutaneous muscle, traditionally considered vestigial in humans, and ask whether the panniculus may play a role in the chronicity and reinjury of heel PUs. To determine whether humans have a panniculus muscle layer at the heel, we dissected eight cadavers. To assess the influence of the panniculus layer on PU, we performed computational simulations of supine weight bearing. Finally, we assessed panniculus regeneration in fluorescent mice. Results show a panniculus layer present in all cadavers examined. Simulations show a thin layer of panniculus muscle causes a dramatic decrease in the volume of soft tissue experiencing high strain and stress, compared to a heel without a panniculus. Importantly, in the mouse model, the panniculus fails to regenerate after PU, even when other cutaneous layers had fully regenerated. Our work shows that the panniculus is able to redistribute load around the heel bone, which might allow it to prevent PUs. Moreover, it is highly susceptible to incomplete regeneration after PU. Poor panniculus regeneration after PU might be a predictive anatomical biomarker for recurrence, and this biomarker should be evaluated prospectively in future clinical trials.
Facial asymmetry tracks genetic diversity amongGorillasubspecies
Authors: McGrath Kate , Eriksen Amandine B. , García-Martínez Daniel , Galbany Jordi , Gómez-Robles Aida , Massey Jason S. , Fatica Lawrence M. , Glowacka Halszka , Arbenz-Smith Keely , Muvunyi Richard , Stoinski Tara S. , Cranfield Michael R. , Gilardi Kirsten , Shalukoma Chantal , de Merode Emmanuel , Gilissen Emmanuel , Tocheri Matthew W. , McFarlin Shannon C. , Heuzé Yann
Published: February 2022

Mountain gorillas are particularly inbred compared to other gorillas and even the most inbred human populations. As mountain gorilla skeletal material accumulated during the 1970s, researchers noted their pronounced facial asymmetry and hypothesized that it reflects a population-wide chewing side preference. However, asymmetry has also been linked to environmental and genetic stress in experimental models. Here, we examine facial asymmetry in 114 crania from threeGorillasubspecies using 3D geometric morphometrics. We measure fluctuating asymmetry (FA), defined as random deviations from perfect symmetry, and population-specific patterns of directional asymmetry (DA). Mountain gorillas, with a current population size of about 1000 individuals, have the highest degree of facial FA (explaining 17% of total facial shape variation), followed by Grauer gorillas (9%) and western lowland gorillas (6%), despite the latter experiencing the greatest ecological and dietary variability. DA, while significant in all three taxa, explains relatively less shape variation than FA does. Facial asymmetry correlates neither with tooth wear asymmetry nor increases with age in a mountain gorilla subsample, undermining the hypothesis that facial asymmetry is driven by chewing side preference. An examination of temporal trends shows that stress-induced developmental instability has increased over the last 100 years in these endangered apes.
Sutcliffiella deserti sp. nov., isolated from desert soil
Authors: Bai Pengze , Zhang Siyue , Chen Ya , Ping Weiwei , Pang Huancheng , Du Jie , Li Yuyi , Zhang Jianli
Published: February 2022

A Gram-stain-positive, facultative anaerobic, motile and rod-shaped bacterial strain, DG-18T, was isolated from desert soil sampled at the Kubuqi Desert in Inner Mongolia, China. Strain DG-18T grew at 4–40 °C (optimum, 25–30 °C), at pH 8.0–10.0 (optimum, pH 9.0) and with 0–8.0 % (w/v) NaCl (optimum 2.0%). 16S rRNA gene sequence analysis placed strain DG-18T within the genus

Sutcliffiella

of the family

Bacillaceae

with

Sutcliffiella halmapala

DSM 8723T (98.2%),

Sutcliffiella zhanjiangensis

JSM 099021T (97.6%),

Sutcliffiella horikoshii

DSM 8719T (97.4%),

Sutcliffiella catenulata

18CT (96.6 %) and

Sutcliffiella cohnii

NBRC 15565T (96.5%) as its closest relatives. The major respiratory quinone of strain DG-18T was MK-7 and the major polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. Its major fatty acids were iso-C15 : 0 and iso-C17 : 1
 ω10c. The genomic DNA G+C content of strain DG-18T was 38.7 mol% based on total genome calculations. The average nucleotide identity score between the genomic sequence of strain DG-18T and that of

S. halmapala

DSM 8723T was 76.7 %. The Genome-to-Genome Distance Calculator showed that the DNA–DNA hybridization value for strain DG-18T and

S. halmapala

DSM 8723T was 21.8%. Based on the polyphasic taxonomic data, strain DG-18T represents a novel species of the genus

Sutcliffiella

, for which the name Sutcliffiella deserti sp. nov. is proposed. The type strain is DG-18T (=GDMCC 1.17773T=KCTC 43170T).
MolEvolvR: A web-app for characterizing proteins using molecular evolution and phylogeny
Authors: Krol Jacob D , Burke Joseph T , Chen Samuel Z , Sosinski Lo M , Alquaddoomi Faisal S , Brenner Evan P , Wolfe Ethan P , Rubinetti Vincent P , Amolitos Shaddai , Reason Kellen M , Johnston John B , Ravi Janani
Published: February 2022

Studying proteins through the lens of evolution can reveal conserved features, lineage-specific variants, and their potential functions. MolEvolvR (https://jravilab.org/molevolvr) is a novel web-app enabling researchers to visualize the molecular evolution of their proteins of interest in a phylogenetic context across the tree of life, spanning all superkingdoms. The web-app accepts multiple input formats — protein/domain sequences, homologous proteins, or domain scans — and, using a general-purpose computational workflow, returns detailed homolog data and dynamic graphical summaries (e.g., phylogenetic trees, multiple sequence alignments, domain architectures, domain proximity networks, phyletic spreads, co-occurrence patterns across lineages). In addition to whole protein searches, MolEvolvR can perform domain-wise analyses. Thus, MolEvolvR is a powerful, easy-to-use web interface for computational protein characterization.
A role for Nucleocapsid-specific antibody function in Covid-19 Convalescent plasma therapy
Authors: Herman Jonathan D. , Wang Chuangqi , Burke John Stephen , Zur Yonatan , Compere Hacheming , Kang Jaewon , Macvicar Ryan , Shin Sally , Frank Ian , Siegel Don , Tebas Pablo , Choi Grace H. , Shaw Pamela A. , Yoon Hyunah , Pirofski Liise-anne , Juelg Boris , Bar Katharine J. , Lauffenburger Douglas , Alter Galit
Published: February 2022

COVID-19 convalescent plasma (CCP), a passive polyclonal antibody therapeutic, has exhibited mixed results in the treatment of COVID-19. Given that the therapeutic effect of CCP may extend beyond the ability of SARS-CoV-2-specific antibody binding and neutralization to influence the evolution of the endogenous antibody response, we took a systematic and comprehensive approach to analyze SARS-CoV-2 functional antibody profiles of participants in a randomized controlled trial of CCP treatment of individuals hospitalized with COVID-19 pneumonia where CCP was associated with both decreased mortality and improved clinical severity. Using systems serology, we found that the clinical benefit of CCP is related to a shift towards reduced inflammatory Spike (S) responses and enhanced Nucleocapsid (N) humoral responses. We found CCP had the greatest clinical benefit in participants with low pre-existing anti-SARS-CoV-2 antibody function, rather than S or N antibody levels or participant demographic features. Further, CCP induced immunomodulatory changes to recipient humoral profiles persisted for at least two months, marked by the selective evolution of anti-inflammatory Fc-glycan profiles and persistently expanded nucleocapsid-specific humoral immunity following CCP therapy. Together, our findings identify a novel mechanism of action of CCP, suggest optimal patient characteristics for CCP treatment, identify long-last immunomodulatory effects of CCP, and provide guidance for development of novel N-focused antibody therapeutics for severe COVID-19 hyperinflammation.
Accuracy of Attestation Among Mohs and Dermatologic Surgery Diplomates
Authors: Perlis Clifford S. , Perlis Roy H.
Published: February 2022

Self-regulation is a key tenet of professionalism. We sought to assess the accuracy of self-attestation with respect to the administration of a newly defined field of board sub-specialization. One qualifying pathway to take the written examination for certification in Mohs and Dermatologic Surgery (MDS) is to self-attest to an active practice of Mohs Surgery. Utilizing publicly available data, we find that greater than 6% (111) of new diplomates did not complete an ACGME-approved fellowship or charge CMS in 2019 for greater than one Mohs case per week. In addition, 72 individuals did not complete a fellowship or charge CMS in 2019 for a single Mohs case. This discrepancy between the test qualifications and practice patterns evident from CMS data suggests concern for the reliability of self-regulation in this setting.
Community-based Case Studies of Vaccine Hesitancy and the COVID-19 Response in South Africa; The VaxScenes Study
Authors: Wiysonge Charles Shey , Coulson Nancy , Pillay Nirvana , Cooper Sara , Groenewald Candice , Essack Zaynab , Parker Saahier , Houston Gregory , Simmonds Jane , Jaca Anelisa , Mutemwa Muyunda , Katoto Patrick DMC , van Rooyen Heidi
Published: February 2022

Background

South Africa has reported more than half of all COVID-19 cases and deaths in Africa. The South African government has launched a large COVID-19 immunization campaign with the goal of reaching more than 40 million individuals. Nonetheless, certain international, largely internet-based surveys have shown a significant proportion of vaccine hesitancy in South Africa. This study aims to determine and co-create with local stakeholders a comprehensive understanding of vaccine hesitancy and opportunities to support the promotion of other COVID-19 health-promoting behaviours at community level.

Methods and design

A mixed-methods, multiple case-study design; informed by the socio-ecological model of behaviour change. Four socio-economically diverse communities across South Africa will be selected and data collection will take place concurrently through three iterative phases. Phase 1 will provide insights into community experiences of COVID-19 (response) through desktop mapping exercises, observations, in-depth interviews, and focus group discussions (FGDs) designed as expression sessions with local stakeholders. Phase 2 will explore the extent and drivers of community acceptance of COVID-19 vaccines. This phase will comprise a quantitative survey based on WHO’s Behavioural and Social Drivers of Vaccination tool as well as further FGDs with community members. Phase 3 will involve cross-case study syntheses and presentation of findings to national role-players.

Discussion

This study will provide ground up, locally responsive, and timeous evidence on the factors influencing COVID-19 health-seeking behaviours to inform ongoing management and mitigation of COVID-19 in South Africa. It will also provide insights into the applicability of a novel vaccine hesitancy model in Africa.
Methylome analysis for prediction of long and short-term survival in glioblastoma patients from the Nordic trial
Authors: Łysiak Małgorzata , Das Jyotirmoy , Malmström Annika , Söderkvist Peter
Published: February 2022

Patients with glioblastoma (GBM) have a short survival, but even among patients receiving the same therapies and with good prognostic factors, one can find those with exceptionally short and long survival.

In the Nordic trial, patients with GBM, 60 years or older, were randomized between 2 radiotherapy arms or TMZ. We selected 59 patients, equally distributed between the 3 treatment arms and MGMT promoter methylation status, with good prognostic factors, but with short or long survival. We performed methylation profiling with the Illumina Infinium Methylation EPIC BeadChip arrays in conjunction with a methylation-based CNS tumor classifier, analysis of differentially methylated CpG sites (DMCs) and pathway enrichment analysis.

Samples classified as non-GBM IDH wildtype were excluded and in the analysis of long vs. short survivors with documented progression or tumor-related death, we found DMCs in the TMZ, MGMT promoter methylated group (123,510), as well as in the 60Gy, MGMT promoter unmethylated group (4,086) and 34Gy, MGMT promoter methylated group (39,649). The joint analysis of the RT arms revealed 319 DMCs in the MGMT unmethylated group but no differences for MGMT promoter methylated samples, or in any of the analyses independent of MGMT status. Interestingly, in the long-term survivors with methylated MGMT promoter treated with TMZ we found hypermethylation of the Wnt signaling and the platelet activation, signaling and aggregation pathways.

We identified DMCs for both TMZ and RT treated patients. Further systematic analysis of larger patient cohorts is necessary for confirmation of their predictive properties.
The application of Raman spectroscopy and chemometric methods for analysis healthy blood and blood with BRCA mutation
Authors: Kopec M. , Romanowska-Pietrasiak B. , Abramczyk H.
Published: February 2022

Presented study included human blood from heathy patients and from patients with BRCA mutation. Raman spectroscopy can be used for BRCA mutation detection and bioanalytical characterization of pathologically changed samples. The aim of this study is to evaluate the Raman biomarkers to distinguish blood samples from healthy patients and from patient with BRCA mutation by Raman spectroscopy. We have proved that Raman spectroscopy is a powerful technique to distinguish between healthy blood and blood with BRCA mutation and to characterize biochemical composition of samples. Partial Least Squares Discriminant Analysis yielded effective and comparable samples classification based on vibrational features. The sensitivity and specificity obtained from PLS-DA have been over 86.5%. The obtained results confirm clinical potential of Raman spectroscopy in oncological diagnostics.

Graphical Abstract
Tackling the first COVID-19 wave at the Cape Town Hospital of Hope: Why was it such a positive experience for staff?
Authors: Reid Steve , Nana Mitan , Abrahams Theo , Hussey Nadia , Okun-Netter Ronit , Ras Tasleem , von Pressentin Klaus
Published: February 2022

Background

In contrast to alarming reports of exhaustion and burnout amongst healthcare workers in the first wave of the COVID-19 pandemic, we noticed surprisingly positive staff experiences of working in a COVID-19 field hospital in South Africa. The 862-bed ‘Hospital of Hope’ was established at the Cape Town International Convention Centre specifically to cope with the effects of the first wave of the COVID-19 pandemic in Cape Town.

Methods

We aimed to systematically describe and assess the effects on staff and the local health system. A cross-sectional descriptive study design was employed using mixed methods including record reviews and interviews with key informants.

Results

Quantitative results confirmed high job satisfaction and low staff infection rates. The emerging themes from the qualitative data are grouped around a “bull’s eye” of the common purpose of person-centredness, from both patient and staff perspectives, and include staff safety and support, rapid communication, continuous learning and adaptability, underpinned by excellent teamwork. The explanations for the positive feedback included good disaster planning, adequate resources, and an extraordinary responsiveness to the need.

Conclusions

The ‘Hospital of Hope’ staff experience produced significant learnings for the design and management of routine health services outside of a disaster situation. The adaptability and responsiveness of the facility and its staff was largely a product of the unprecedented nature of the pandemic, but such approaches could benefit routine health services enormously, as individual hospitals and health facilities realize their place in a system that is ‘more than the sum of its parts’.
Breast and colorectal cancer awareness in Malaysians and barriers towards screening: A systematic review
Authors: Paramasivam Darishiani , Schliemann Désirée , Dahlui Maznah , Donnelly Michael , Su Tin Tin
Published: February 2022

Background

Breast cancer (BC) and colorectal cancer (CRC) are considered primary cancers that affect both male and females globally. In Malaysia, BC is the most commonly diagnosed cancer among women of all ethnic groups and CRC is the second most common cancer in males and the second most common cancer in females. This systematic review was carried out to assess cancer symptom awareness and barriers to undergoing cancer screening for BC and CRC.

Methods

A pre-defined search was conducted between January 2008 and December 2018 using the following databases: MEDLINE, Embase, CINAHL, Web of Science, PsycINFO, Scopus and Cochrane Library for relevant articles. The search was updated in June 2020. Reviewers independently performed the data extraction and quality assessment of the included study according to the Joanna Briggs Institute assessment tools.

Result

22 studies met the inclusion criteria (BC n=11; CRC n=11). Nine studies assessed symptom knowledge for BC and eight for CRC. Two studies described barriers towards cancer screening for BC and one for CRC. Four CRC studies assessed symptoms knowledge and cancer screening barriers. The most commonly reported BC symptoms were ‘painless breast lump’(27.6% - 90.8%), ‘nipple discharge’ (1.6% - 74.5%) and ‘pain in breast/ breast region’ (11.5% - 82.8%) meanwhile CRC symptoms were ‘change in bowel habits (new-onset diarrhoea or constipation)’ (28.4% - 86.6%), ‘bleeding and/or bleeding from the back passage’ (11.5% - 71.9%) and ‘weight loss’ (9.3% - 83.4%). ‘Financial issue’ (10% - 17.5%) was the most frequent blockade identified towards BC screening meanwhile ‘fear of result’ (27.6% - 32.1%) for CRC screening by Malaysians. Overall the studies carried out in Malaysia, six studies on BC symptom knowledge and one study on BC screening barrier were scored as medium study quality while four studies on CRC symptom knowledge and three studies on CRC screening barriers were scored as medium study quality.

Conclusion

Studies described varied and overall, limited, symptom awareness and barriers towards BC and CRC screening which likely contributes to the delayed presentation of cancers in Malaysia. There is a need for improving the awareness of BC and CRC symptoms as well as the importance of screening to encourage the early presentation of symptomatic cancer patients and down-staging of cancer.
piRNA-like small RNAs target transposable elements in a Clade IV parasitic nematode
Authors: Suleiman Mona , Kohnosu Asuka , Murcott Ben , Dayi Mehmet , Pawluk Rebecca , Yoshida Akemi , Viney Mark , Kikuchi Taisei , Hunt Vicky L.
Published: February 2022

The small RNA (sRNA) pathways identified in the model organism Caenorhabditis elegans are not widely conserved across nematodes. For example, the PIWI pathway and PIWI-interacting RNAs (piRNAs) are involved in regulating and silencing transposable elements (TE) in most animals but have been lost in nematodes outside of the Caenorhabditis elegans group (Clade V), and little is known about how nematodes regulate TEs in the absence of the PIWI pathway. Here, we investigated the role of sRNAs in the Clade IV parasitic nematode Strongyloides ratti by comparing two genetically identical adult stages (the parasitic female and free-living female). We identified putative small-interfering RNAs, microRNAs and tRNA-derived sRNA fragments that are differentially expressed between the two adult stages. Two classes of sRNAs were predicted to regulate TE activity including (i) a parasite-associated class of 21-22 nt long sRNAs with a 5’ uracil (21-22Us) and monophosphate modification, and (ii) 27 nt long sRNAs with a 5’ guanine/adenine (27GAs) and polyphosphate modification. The 21-22Us show striking resemblance to the 21U PIWI-interacting RNAs found in C. elegans, including an AT rich upstream sequence, overlapping loci and physical clustering in the genome.
A Novel Chronic in vivo Oral Cadmium Exposure-Washout Mouse Model for Studying Cadmium Toxicity and Complex Diabetogenic Effects
Authors: Wong Winifred P.S. , Wang Janice C. , Meyers Matthew S. , Wang Nathan J. , Sponenburg Rebecca A. , Allen Norrina B. , Edwards Joshua E. , El Muayed Malek
Published: February 2022

Type II diabetes mellitus (T2DM) is characterized by insulin resistance, β-cell dysfunction and hyperglycemia. In addition to well known risk factors such as lifestyle and genetic risk score, accumulation of environmental toxicants in organs relevant to glucose metabolism is increasingly recognized as additional risk factors for T2DM. Here, we describe the development of an in vivo oral cadmium (Cd) exposure model. It was shown that oral Cd exposure in drinking water followed by washout and high fat diet (HFD) in C57BL/6N mice results in islet Cd bioaccumulation comparable to that found in native human islets while mitigating the anorexic effects of Cd to achieve the same weight gain required to induce insulin resistance as in Cd naïve control mice. Inter individual variation in plasma glucose and insulin levels as well as islet Cd bioaccumulation was observed in both female and male mice. Regression analysis showed an inverse correlation between islet Cd level and plasma insulin following a glucose challenge in males but not in females. This finding highlights the need to account for inter individual target tissue Cd concentrations when interpreting results from in vivo Cd exposure models. No effect of Cd on insulin secretion was observed in islets ex vivo, highlighting differences between in vivo and ex vivo cadmium exposure models. In summary, our oral in vivo Cd exposure-washout with HFD model resulted in islet Cd bioaccumulation that is relevant in the context of environmental cadmium exposure in humans. Here, we showed that islet Cd bioaccumulation is associated with complex cadmium-mediated changes in glucose clearance and β-cell function. The model described here will serve as a useful tool to further examine the relationship between Cd exposure, islet Cd bioaccumulation, dysglycemia and their underlying mechanisms.
Truvari: Refined Structural Variant Comparison Preserves Allelic Diversity
Authors: English Adam C. , Menon Vipin K. , Gibbs Richard , Metcalf Ginger A. , Sedlazeck Fritz J.
Published: February 2022

For multi-sample structural variant analyses like merging, benchmarking, and annotation, the fundamental operation is to identify when two SVs are the same. Commonly applied approaches for comparing SVs were developed alongside technologies which produce ill-defined boundaries. As SV detection becomes more exact, algorithms to preserve this refined signal are needed. Here we present Truvari - a SV comparison, annotation and analysis toolkit - and demonstrate the effect of SV comparison choices by building population-level VCFs from 36 haplotype-resolved long-read assemblies. We observe over-merging from other SV merging approaches which causes up to a 2.2x inflation of allele frequency relative to Truvari.
Functional networks of the human bromodomain-containing proteins
Authors: Gao Cong , Glass Karen C. , Frietze Seth
Published: February 2022

Background

Bromodomains are a structurally conserved epigenetic reader domain that bind to acetylated lysine residues in both histone and non-histone proteins. Bromodomain-containing proteins (BRD proteins) function are established scaffolds in the assembly of multi-protein complexes to regulate diverse biological processes. BRD proteins have been classified based on biological and functional similarity, however the functions of many BRD proteins remains unknown. PPI network analysis is useful for revealing organizational roles, identifying functional clusters, and predicting function for BRD proteins.

Results

We used available data to construct protein-protein interaction networks (PPINs) to study the properties of the human bromodomain protein family. The network properties of the BRD PPIN establishes that the BRD proteins serve as hub proteins that are enriched near the global center to form an inter-connected PPIN. We identified dense subgraphs formed by BRD proteins and find that different BRD proteins share topological similarity and functional associations. We explored the functional relationships through clustering and Hallmark pathway gene set enrichment analysis and identify potential biological roles for different BRD proteins.

Conclusions

In our network analysis we confirmed that BRD proteins are conserved central nodes in the human PPI network and function as scaffolds to form distinctive functional clusters. Overall, this study provides detailed insight into the predictive functions of BRD proteins in the context of functional complexes and biological pathways.
Nucleosome conformation dictates the histone code
Authors: Marunde Matthew R. , Fuchs Harrison A. , Burg Jonathan M. , Popova Irina K. , Vaidya Anup , Hall Nathan W. , Meiners Matthew J. , Watson Rachel , Howard Sarah A. , Novitzky Katherine , McAnarney Eileen , Cheek Marcus A. , Sun Zu-Wen , Venters Bryan J. , Keogh Michael-C. , Musselman Catherine A.
Published: February 2022

Histone post-translational modifications (PTMs) play a critical role in chromatin regulation. It has been proposed that these PTMs form localized ‘codes’ that are read by specialized regions (reader domains) in chromatin associated proteins (CAPs) to regulate downstream function. Substantial effort has been made to define [CAP-histone PTM] specificity, and thus decipher the histone code / guide epigenetic therapies. However, this has largely been done using a reductive approach of isolated reader domains and histone peptides, with the assumption that PTM readout is unaffected by any higher order factors. Here we show that CAP-histone PTM interaction is in fact dependent on nucleosome context. Our results indicate this is due to histone tail accessibility and the associated impact on binding potential of reader domains. We further demonstrate that the in vitro specificity of a tandem reader for PTM-defined nucleosomes is recapitulated in a cellular context. This necessitates we refine the ‘histone code’ concept and interrogate it at the nucleosome level.
A highly sensitive LC-MS/MS method for quantitative determination of 7 vitamin D metabolites in mouse brain tissue
Authors: Stephenson Andrea , Hunter Ben , Shaw Paul Nicholas , Abu Kassim Nur Sofiah , Trengrove Rob , Takechi Ryu , Lam Virginie , Mamo John
Published: February 2022

Despite its critical role in neurodevelopment and brain function, vitamin-D (vit-D) homeostasis, metabolism and kinetics within the central nervous system remain largely undetermined. Thus, it is of critical importance to establish an accurate, highly sensitive and reproducible method to quantitate vit-D in brain tissue. Here, we present a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method and for the first time, demonstrate detection of seven major vit-D metabolites in brain tissues of C57BL/6J wild-type mice, namely: 1,25(OH)2D3, 3-epi-1,25(OH)2D3, 1,25(OH)2D2, 25(OH)D3, 25(OH)D2, 24,25(OH)2D3, and 24,25(OH)2D2. Chromatographic separation was achieved on a pentaflurophenyol column 3 mM ammonium formate with water/methanol [A] and methanol/isopropanol [B] phases. Detection was by positive-ion electrospray tandem mass spectrometry. We used calibration standards of each metabolite prepared in brain matrices to validate the detection range, precision, accuracy and recovery. Isotopically labelled analogues, 1,25(OH)2D3-d3, 25(OH)D3-C5 and 24,25(OH)2D3-d6, served as the internal standards for the closest molecular related metabolite in all measurements. The calibration range was between 1 fg/mL to 10 ng/mL with an LLOD and LLOQ of 10 fg/mL and 3 fg/mL, respectively. The intra-/inter-day precision and accuracy for measuring brain vit-D metabolites ranged between 0.12-11.53% and 0.28-9.11%, respectively. Recovery ranged between 99.06% and 106.9% for all metabolites. Collectively, the sensitivity and efficiency of our method supersedes previously reported protocols used to measure vit-D and to our knowledge, the first protocol to reveal the abundance of 25(OH)D2, 1,25(OH)D2 and 24,25(OH)2D2, in brain tissue of any species. This technique may be important in supporting the future advancement of pre-clinical research into the function of vit-D in neurophysiological, neuropsychiatric, and neurodegeneration.
Association Between Cannabis Smoking and Academic Achievement in Colombian High-School Students
Authors: Pérez-Martínez Yegson , Ceballos-Ospino Guillermo Augusto , Campo-Arias Adalberto
Published: February 2022

Background

Cannabis smoking can affect academic achievement, and depressive symptoms and family dysfunction are also associated it. The study’s objective was to establish the relationship between cannabis smoking and academic achievement, controlling clinically important depressive symptoms and family dysfunction.

Methods

A cross-sectional study was designed. The authors quantified lifetime cannabis smoking, perception of academic achievement, clinically important depressive symptoms, and family dysfunction. The crude association between cannabis smoking and academic achievement was computed; after it was adjusted by clinically important depressive symptoms and family dysfunction.

Results

1,462 students between 13 and 17 participated in the research; 11.6% reported lifetime cannabis smoking, 30.8% poor-fair academic achievement; 7.1% clinically important depressive symptoms; and 76.1% family dysfunction. Lifetime cannabis smoking was significantly associated with poor-fair academic achievement after adjusting for clinically important depressive symptoms and family dysfunction (OR = 1.61, 95%CI 1.16 - 2.24).

Conclusions

Lifetime cannabis smoking is related to poor-fair academic achievement among high-school students in Santa Marta, Colombia.

Data availability statement

The data supporting this study’s findings are available from the corresponding author upon reasonable request.

Authors biography

Yegson Pérez-Martínez

He is a young psychologist interested in researching school psychology, academic achievement, and health-compromising behaviours.

Guillermo Augusto Ceballos-Ospino, psychologist He is a psychologist and occasional professor at the Program of Psychology, University of Magdalena, Santa Marta, Colombia. His action areas are mental health, especially suicide prevention, and psychometrics. He is interested in studies with populations of university students.

Adalberto Campo-Arias, MD, MSc He is a psychiatrist, magister in sexual and reproductive health and professor at the School of Medicine, Faculty of Health Science, University of Magdalena, Santa Marta, Colombia. His research interests include sexual and reproductive health, human rights, prejudice and discrimination, and health-compromising behaviours.