bluuebunny/crossref_metadata_2025 huggingface dataset:
Translation and Cross-cultural Adaptation of the Self-care of Hypertension Inventory for Thais With Hypertension
Authors: Phonphet Chennet , Suwanno Jom , Thiamwong Ladda , Mayurapak Chidchanok , Ninla-aesong Putrada
Published: January 2022

Background

Self-care is essential for treating hypertension by lowering and controlling blood pressure, to ultimately reduce cardiovascular disease. A valid and reliable hypertension self-care measure is needed for the Thai population.

Objective

The aim of this study was to translate a cross-cultural adaptation of the Self-care of Hypertension Inventory (SC-HI) into Thai and conduct a pretest of the Thai SC-HI (version 2.0).

Methods

We performed a methodological study. The stepped approach included translation of the original version of the SC-HI into Thai (forward), synthesis of translation, translation of the Thai version back to English, expert committee review, and pretesting. Pretest phase for feasibility, interobserver agreement, and temporal stability tests were performed in 140 patients with hypertension.

Results

Translation equivalence was obtained between the Thai and the original US versions. The item-level content validity index was rated by 9 experts; the relevance, clarity, simplicity, and ambiguity criteria were all 1.00. Similarly, the scale-level content validity indices were 1.00 for the overall instrument and the self-care maintenance, self-care management, and self-care confidence scales. The item-level intraclass correlation coefficients (ICCs) had a range of 0.97 to 1.00 for interobserver agreement and 0.95 to 1.00 for test-retest, respectively. The interobserver ICCs were 0.99 for the total scale and 3 separate scales. The test-retest ICCs were 0.99 for the total scale, with a range of 0.97 to 0.99 for the three separate scales.

Conclusion

The process of cross-cultural adaptation warranted validity and reliability testing of the Thai SC-HI. Psychometric testing of this instrument is needed for evaluation in a large sample of individuals with hypertension.
Peripheral Skeletal Muscle Impairment in Children After Treatment for Leukemia and Lymphoma
Authors: White Gillian E. , West Sarah L. , Sabiston Catherine , Rhind Shawn G. , Nathan Paul C. , Caterini Jessica E. , Jones Heather , Rayner Tammy , Weiss Ruth , Wells Greg D.
Published: January 2022

Exercise intolerance is a common adverse effect of childhood cancer, contributing to impaired health and well-being. While reduced aerobic fitness has been attributed to central cardiovascular deficiencies, the involvement of peripheral musculature has not been investigated. We studied peripheral muscle function in children following cancer treatment using noninvasive phosphorus-31 magnetic resonance spectroscopy. Ten acute lymphoblastic leukemia (ALL) and 1 lymphoma patient 8 to 18 years of age who completed treatment 6 to 36 months prior and 11 healthy controls participated in the study. Phosphorus-31 magnetic resonance spectroscopy was used to characterize muscle bioenergetics at rest and following an in-magnet knee-extension exercise. Exercise capacity was evaluated using a submaximal graded treadmill test. Both analysis of variance and Cohen d were used as statistical methods to determine the statistical significance and magnitude of differences, respectively, on these parameters between the patient and control groups. The patients treated for ALL and lymphoma exhibited lower anaerobic function (P=0.14, d=0.72), slower metabolic recovery (P=0.08, d=0.93), and lower mechanical muscle power (d=1.09) during exercise compared with healthy controls. Patients demonstrated lower estimated VO2peak (41.61±5.97 vs. 47.71±9.99 mL/min/kg, P=0.11, d=0.76), lower minutes of physical activity (58.3±35.3 vs. 114.8±79.3 min, P=0.12, d=0.99) and higher minutes of inactivity (107.3±74.0 vs. 43.5±48.3 min, d=1.04, P<0.05). Children treated for ALL and lymphoma exhibit altered peripheral skeletal muscle metabolism during exercise. Both deconditioning and direct effects of chemotherapy likely contribute to exercise intolerance in this population.
Bone Health in Osteosarcoma at Presentation and Its Impact on Cancer Treatment: A Case Series of 3 Pediatric Patients
Authors: Malcolmson Caroline , Lautatzis Maria-Elena , Malkiel Sarah , Lenherr-Taube Nina , Traubici Jeffery , Gupta Abha , Hopyan Sevan , Sochett Etienne , Grant Ronald
Published: January 2022

Osteosarcoma is the most common pediatric malignant bone tumor. Concomitant osteoporosis has typically been attributed to oncologic therapy. The present case series is aimed to describe 3 patients who presented with osteoporosis or osteopenia before, or early in, their oncology treatment. In our patients, bone health and its complications had significant impacts including pain, reduced mobility, prolonged admission, and delays in recovery. Our patients experienced improvement with resection of their primary tumor and with bisphosphonate infusion. Future studies are required to determine the prevalence osteoporosis at presentation of osteosarcoma and the role of bisphosphonates.
Documented Viral Illness at the Time of Splenic Sequestration Does Not Affect the Odds of Recurrence in Children With Sickle Cell Disease
Authors: Clement Omoyeni , Fishbein Joanna , Appiah-Kubi Abena , Aygun Banu
Published: January 2022

This retrospective study investigates the relationship between the presence of a documented viral infection in children with sickle cell disease during their first splenic sequestration crisis and their odds of recurrence. Forty-eight children were admitted to our hospital between 2008 and 2018 with a splenic sequestration crisis. Thirty-six had respiratory viral panels done on admission, 13 of whom were positive. Two additional children were diagnosed with parvovirus B19 infection by serology. The recurrence rate was 52% (17/33) for those deemed negative for viral illness compared with 33% (5/15) among those with a positive documented viral illness, which was not statistically different (P=0.35). HbSC genotype decreased, and reticulocytosis increased the odds of recurrence. Further research is needed to substantiate these findings.
Intensive Multimodal Therapy Combined With Long-term Temozolomide and Etoposide Treatment for Recurrent Osteosarcoma to the Liver and Stomach
Authors: Umeda Katsutsugu , Taura Kojiro , Kato Itaru , Saida Satoshi , Hiramatsu Hidefumi , Shimizu Hironori , Nakamoto Yuji , Uto Megumi , Mizowaki Takashi , Sakamoto Akio , Adachi Souichi , Okamoto Takeshi , Takita Junko
Published: January 2022

The prognosis of patients with osteosarcoma recurring at extrapulmonary/extraosseous sites, especially those with unresectable tumors, is generally dismal due to high resistance to chemotherapy. The present study describes a pediatric patient with osteosarcoma recurring to the liver and stomach. Complete remission was achieved by long-term systemic chemotherapy with temozolomide+etoposide, local irradiation of the stomach, and radical surgical removal of multiple liver metastases following percutaneous transhepatic portal embolization. Second-line multimodal therapy, consisting of salvage chemotherapy and curative local treatment of metastases, may enhance disease-free survival of patients with osteosarcoma experiencing relapse to uncommon sites.
Surgical Treatment for Pneumothorax and Tumor-bronchial Fistula Secondary to Pulmonary Metastasis of Osteosarcoma in Pediatric and Adolescent Patients
Authors: Kawakubo Naonori , Hishiki Tomoro , Arakawa Ayumu , Nakajima Miho , Kumamoto Tadashi , Nakagawa Kazuo , Kawai Akira , Ogawa Chitose
Published: January 2022

Background:

Pneumothorax and tumor-bronchial fistula are rare complications of pulmonary metastasis of osteosarcoma.

Observations:

We herein report the cases of 3 pediatric and adolescent patients who developed pneumothorax or tumor-bronchial fistula during treatment of pulmonary metastasis of osteosarcoma with chemotherapeutics or antiangiogenic agents. Two patients developed pneumothorax, and the other patient developed tumor-bronchial fistula. All of the patients finally underwent the surgery to treat their complications.

Conclusions:

Although it is not a curative surgery, surgery for pneumothorax and tumor-bronchial fistula is acceptable. The operative procedure should be considered on the basis of the predicted prognosis of the patient.
Perinatal Care of Childhood Sexual Abuse Survivors
Authors: Head Morgan L. , Heck Jennifer L.
Published: January 2022

Background:

An estimated one in nine women seeking perinatal care is a survivor of childhood sexual abuse (CSA), yet CSA may be unknown to nurses and other health care providers. Childhood sexual abuse can have adverse physical and psychological effects for survivors, and the intimacy of perinatal care can trigger distress like intrusive thoughts.

Purpose:

To explore available literature about CSA survivors and perinatal care. Specific aims were to 1) identify nursing actions that ease undesirable feelings during perinatal care for CSA survivors and 2) identify gaps in the literature on perinatal care for CSA survivors.

Study Design and Methods:

Following the PRISMA-ScR Checklist, MEDLINE and CINAHL databases were searched using: “Child Abuse, Sexual,” “Perinatal Care,” and “Parturition.” Initial yield was 109 records.

Results:

Applying inclusion and exclusion criteria produced 14 full-text articles. Findings suggest that obtaining consent, promoting safety, trust, and control, fostering a healthy nurse–patient relationship, and inquiring about abuse may improve how CSA survivors experience perinatal care. Gaps in literature include nursing assessments for history of CSA with nonverbal cues.

Clinical Implications:

For all patients, nurses should foster security and trust. It is critical that CSA survivors be in control of their care. Procedures should be thoroughly explained, and most importantly, consent should be obtained prior to every physical touch. Nurses must ask about history of CSA because it is part of patient-centered care, which is central to nursing.
Prevalence of Burnout Among Cardiothoracic Radiologists
Authors: Eisenberg Ronald L. , Sotman Timothy E. , Czum Julianna M. , Montner Steven M. , Meyer Cristopher A.
Published: January 2022

Purpose:

We investigated the impact of modality-specific volumes and other potential stressors on burnout and career-choice satisfaction.

Materials and Methods:

An anonymous survey of 36 questions was sent by email to all 875 faculty members of the STR. These included 11 multiple-choice questions, 23 Likert questions, and 2 free-text questions. The Maslach Burnout Index was used to assess the prevalence of the 3 components of burnout (emotional exhaustion, depersonalization, and low professional accomplishment), and we assessed variations among the potential sources of stress with respect to the respondent sex, career stage, and practice setting. Respondents were asked to estimate daily work volume as if interpreting only chest radiographs (CXRs) or only chest/cardiac computed tomography (CT). Statistical analysis was performed using Excel (Microsoft), open-source statistical computing package pandas and SciPy for Python, and Jupyter Notebook, an open-source interactive computing platform.

Results:

Although financial concerns (49.3%), lack of input into decisions (48.6%), and inadequate staffing (45.2%) were additional stressors, the major sources were work-life balance (67.4%) and workload (66.8%), which were more frequently cited by women than men (78.9% vs. 60.8%, P=0.001). Emotional exhaustion and depersonalization were related to higher CXR volumes. Although 83.2% were satisfied being a diagnostic radiologist, 18.8% had thought of leaving medicine. More than half of all radiologists interpreted ≥150 CXRs daily (51.1% vs. 53.6%); more in private practice read ≥200 CXRs (23.2% vs. 14.7%). Of the academic radiologists, 80.2% interpreted 21 to 49 CTs; twice as many in private practice read ≥50 CTs (25.5% vs. 12.7%).

Conclusions:

The contributing factors to cardiothoracic radiologist burnout vary by sex, career stage, and practice setting. Several stressors, especially work-life balance, were associated with higher burnout prevalence. Most respondents expressed career-choice satisfaction. Defining threshold work volumes associated with higher rates of burnout is an important first step in defining burnout prevention guardrails.
Opportunistic Salpingectomy at the Time of Laparoscopic Cholecystectomy for Ovarian Cancer Prevention
Authors: Matsuo Koji , Chen Ling , Matsuzaki Shinya , Mandelbaum Rachel S. , Ciesielski Katharine M. , Silva Jack P. , Klar Maximilian , Roman Lynda D. , Accordino Melissa K. , Melamed Alexander , Elkin Elena , Hershman Dawn L. , Wright Jason D.
Published: January 2022

Objective:

To perform a cost-effectiveness analysis to examine the utility and effectiveness of OS performed at the time of elective cholecystectomy [laparoscopic cholecystectomy (LAP-CHOL)].

Summary Background Data:

OS has been adopted as a strategy to reduce the risk of ovarian cancer in women undergoing hysterectomy and tubal sterilization, although the procedure is rarely performed as a risk reducing strategy during other abdominopelvic procedures.

Methods:

A decision model was created to examine women 40, 50, and 60 years of age undergoing LAP-CHOL with or without OS. The lifetime risk of ovarian cancer was assumed to be 1.17%, 1.09%, and 0.92% for women age 40, 50, and 60 years, respectively. OS was estimated to provide a 65% reduction in the risk of ovarian cancer and to require 30 additional minutes of operative time. We estimated the cost, quality-adjusted life-years, ovarian cancer cases and deaths prevented with OS.

Results:

The additional cost of OS at LAP-CHOL ranged from $1898 to 1978. In a cohort of 5000 women, OS reduced the number of ovarian cancer cases by 39, 36, and 30 cases and deaths by 12, 14, and 16 in the age 40–, 50–, and 60-year-old cohorts, respectively. OS during LAP-CHOL was cost-effective, with incremental cost-effectiveness ratio of $11,162 to 26,463 in the 3 age models. In a probabilistic sensitivity analysis, incremental cost-effectiveness ratio for OS were less than $100,000 per quality-adjusted life-years in 90.5% or more of 1000 simulations.

Conclusions:

OS at the time of LAP-CHOL may be a cost-effective strategy to prevent ovarian cancer among average risk women.
The Problem of Appetite Loss After Major Abdominal Surgery
Authors: Wagner Martin , Probst Pascal , Haselbeck-Köbler Michael , Brandenburg Johanna M. , Kalkum Eva , Störzinger Dominic , Kessler Jens , Simon Joe J. , Friederich Hans-Christoph , Angelescu Michaela , Billeter Adrian T. , Hackert Thilo , Müller-Stich Beat P. , Büchler Markus W.
Published: January 2022

Objective:

To systematically review the problem of appetite loss after major abdominal surgery.

Summary of Background Data:

Appetite loss is a common problem after major abdominal surgery. Understanding of etiology and treatment options is limited.

Methods:

We searched Medline, Cochrane Central Register of Controlled Trials, and Web of Science for studies describing postoperative appetite loss. Data were extracted to clarify definition, etiology, measurement, surgical influence, pharmacological, and nonpharmacological treatment. PROSPERO registration ID: CRD42021224489.

Results:

Out of 6144 articles, we included 165 studies, 121 of which were also analyzed quantitatively. A total of 19.8% were randomized, controlled trials (n = 24) and 80.2% were nonrandomized studies (n = 97). The studies included 20,506 patients undergoing the following surgeries: esophageal (n = 33 studies), gastric (n = 48), small bowel (n = 6), colon (n = 27), rectal (n = 20), hepatobiliary (n = 6), and pancreatic (n = 13). Appetite was mostly measured with the Quality of Life Questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ C30, n = 54). In a meta-analysis of 4 randomized controlled trials gum chewing reduced time to first hunger by 21.2 hours among patients who had bowel surgery. Other reported treatment options with positive effects on appetite but lower levels of evidence include, among others, intravenous ghrelin administration, the oral Japanese herbal medicine Rikkunshito, oral mosapride citrate, multidisciplin-ary-counseling, and watching cooking shows. No studies investigated the effect of well-known appetite stimulants such as cannabinoids, steroids, or megestrol acetate on surgical patients.

Conclusions:

Appetite loss after major abdominal surgery is common and associated with increased morbidity and reduced quality of life. Recent studies demonstrate the influence of reduced gastric volume and ghrelin secretion, and increased satiety hormone secretion. There are various treatment options available including level IA evidence for postoperative gum chewing. In the future, surgical trials should include the assessment of appetite loss as a relevant outcome measure.
Astrocyte biomarker signatures of amyloid-β and tau pathologies in Alzheimer’s disease
Authors: Ferrari-Souza João Pedro , Lukasewicz Ferreira Pâmela C. , Bellaver Bruna , Tissot Cécile , Wang Yi-Ting , Leffa Douglas T. , Brum Wagner S. , Benedet Andréa L. , Ashton Nicholas J. , De Bastiani Marco Antônio , Rocha Andréia , Therriault Joseph , Lussier Firoza Z. , Chamoun Mira , Servaes Stijn , Bezgin Gleb , Kang Min Su , Stevenson Jenna , Rahmouni Nesrine , Pallen Vanessa , Poltronetti Nina Margherita , Klunk William E. , Tudorascu Dana L. , Cohen Annie , Villemagne Victor L. , Gauthier Serge , Blennow Kaj , Zetterberg Henrik , Souza Diogo O. , Karikari Thomas K. , Zimmer Eduardo R. , Rosa-Neto Pedro , Pascoal Tharick A.
Published: January 2022

Astrocytes can adopt multiple molecular phenotypes in the brain of Alzheimer’s disease (AD) patients. Here, we studied the associations of cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP) and chitinase-3-like protein 1 (YKL-40) levels with brain amyloid-β (Aβ) and tau pathologies. We assessed 121 individuals across the aging and AD clinical spectrum with positron emission tomography (PET) brain imaging for Aβ ([18F]AZD4694) and tau ([18F]MK6240), as well as CSF GFAP and YKL-40 measures. We observed that higher CSF GFAP levels were associated with elevated Aβ-PET but not tau-PET load. By contrast, higher CSF YKL-40 levels were associated with elevated tau-PET but not Aβ-PET burden. Structural equation modeling revealed that CSF GFAP and YKL-40 mediate the effects of Aβ and tau, respectively, on hippocampal atrophy, ultimately leading to cognitive impairment. Our results suggest the existence of distinct astrocyte biomarker signatures in response to brain Aβ and tau accumulation, which may contribute to our understanding of the complex link between reactive astrogliosis heterogeneity and AD progression.
Investigating childhood maltreatment as a modifier of genetic risk for cardiovascular disease in the UK Biobank
Authors: Urquijo Helena , Soares Ana Gonçalves , Fraser Abigail , Howe Laura D , Carter Alice R
Published: January 2022

Cardiovascular disease (CVD) is influenced by genetic and environmental factors. Childhood maltreatment is associated with CVD and may modify genetic susceptibility to cardiovascular risk factors. We used genetic and phenotypic data from 100,833 White British UK Biobank participants (57% female; mean age = 55.9 years). We regressed nine cardiovascular risk factors/diseases (alcohol consumption, body mass index [BMI], low-density lipoprotein cholesterol, lifetime smoking behaviour, systolic blood pressure, atrial fibrillation, coronary heart disease, type 2 diabetes, and stroke) on their respective polygenic scores (PGS) and self-reported exposure to childhood maltreatment. Effect modification was tested on the additive and multiplicative scales by including a product term (PGS*maltreatment) in regression models.

On the additive scale, childhood maltreatment accentuated the effect of genetic susceptibility to higher BMI. Individuals not exposed to childhood maltreatment had an increase in BMI of 0.12 SD (95% CI: 0.11, 0.13) per SD increase in BMI PGS, compared to 0.17 SD (95% CI: 0.14, 0.19) in those exposed to all types of childhood maltreatment. On the multiplicative scale, similar results were obtained for BMI though these did not withstand to Bonferroni correction. There was little evidence of effect modification by childhood maltreatment in relation to other outcomes, or of sex-specific effect modification.

Our study suggests the effects of genetic susceptibility to a higher BMI may be moderately accentuated in individuals exposed to childhood maltreatment. However, gene*environment interactions are likely not a major contributor to the excess CVD burden experienced by childhood maltreatment victims.
Graph Convolutional Neural Networks for Histological Classification of Pancreatic Cancer
Authors: Wu Weiyi , Liu Xiaoying , Hamilton Robert B. , Suriawinata Arief A. , Hassanpour Saeed
Published: January 2022

Pancreatic ductal adenocarcinoma has some of the worst prognostic outcomes among various cancer types. Detection of histologic patterns of pancreatic tumors is essential to predict prognosis and decide about the treatment for patients. This histologic classification can have a large degree of variability even among expert pathologists. This study proposes a graph convolutional network-based deep learning model to detect aggressive adenocarcinoma and less aggressive pancreatic tumors from benign cases. Our model uses a convolutional neural network to extract detailed information from every small region in a whole-slide image. Then, we use a graph architecture to aggregate the extracted features from these regions and their positional information to capture the whole-slide level structure and make the final prediction. We evaluated our model on an independent test set and achieved an F1 score of 0.85 for detecting neoplastic cells and ductal adenocarcinoma, significantly outperforming other baseline methods. If validated in prospective studies, this approach has a great potential to assist pathologists in identifying adenocarcinoma and other types of pancreatic tumors in clinical settings.
INCIDENCE OF HEPATITIS B AND C VIRUSES AMONG THE SCAVENGERS IN KWARA STATE, NIGERIA
Authors: Raufu Yusuf Olanrewaju , Olayinka Adewoye Solomon , Olawale Sawyerr Henry , Raimi Morufu Olalekan
Published: January 2022

Background

Poor economic situations in developing nations had made scavenging a means of livelihood for millions of youth and women across the globe. Lack of proper source segregation of wastes in developing countries has increased the potential for the transmission of pathogens like Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV).

Objectives

This study addressed issues relating to waste scavenging, the potential risk in waste scavenging work and seroprevalence of Hepatitis B and C Virus and its relationship with wastes scavenging among wastes scavengers in Kwara State.

Methods

A cross-sectional study was conducted among the scavengers working for major scrap dealers in the three senatorial districts of Kwara State. Consequently, to accomplish the objectives, both primary and secondary data sources were used. The primary data were collected via questionnaires, interviews, blood test and field observations. Whereas the secondary data were extracted from different published and unpublished materials. 240 respondents were administered with questionnaires and undergone hepatitis surface antigen test for both hepatitis B and C in nine of the sixteen local government area in the state. The data were analyzed using statistical package for social science (SPSS version 23) for descriptive and inferential at 5% level of significance. The prevalence of an HBV and HCV infection biological markers (HBsAg and HCsAg) and their associations with exposure to bio-medical waste, socio-demographic factors, and history of occupational injuries was examined.

Results

The seroprevalence of HBV and HCV infection among the scavengers were found to be 8.3% and 5% respectively indicating that scavengers are at risk of HBV and HCV infection.

Conclusions

It was discovered that there are incidences of Hepatitis B and C virus co-infection among scavengers. Also, awareness and compliance to the usage of PPE was found to be an important factor for protection scavengers against the virus. Therefore, vaccination against HBV, enforcement of usage of PPE, good hygiene practices, regular trainings on occupational safety, proper monitoring by regulatory agency and inclusion of scavengers in mandatory health insurance scheme will help to control risk of HBV and HCV infection among scavengers.
A model-based approach to improve intranasal sprays for respiratory viral infections
Authors: Basu Saikat , Akash Mohammad Mehedi Hasan , Lao Yueying , Balivada Pallavi A , Ato Phoebe , Ka Nogaye K , Mituniewicz Austin , Silfen Zachary , Suman Julie , Chakravarty Arijit , Joseph-McCarthy Diane
Published: January 2022

Drug delivery for viral respiratory infections, such as SARS-CoV-2, can be enhanced significantly by targeting the nasopharynx, which is the dominant initial infection site in the upper airway, for example by nasal sprays. However, under the standard recommended spray usage protocol (“Current Use”, or CU), the nozzle enters the nose almost vertically, resulting in sub-optimal deposition of drug droplets at the nasopharynx. Using computational fluid dynamics simulations in two anatomic nasal geometries, along with experimental validation of the generic findings in a different third subject, we have identified a new “Improved Use” (or, IU) spray protocol. It entails pointing the spray bottle at a shallower angle (almost horizontally), aiming slightly toward the cheeks. We have simulated the performance of this protocol for conically injected spray droplet sizes of 1 – 24 μm, at two breathing rates: 15 and 30 L/min. The lower flowrate corresponds to resting breathing and follows a viscous-laminar model; the higher rate, standing in for moderate breathing conditions, is turbulent and is tracked via Large Eddy Simulation. The results show that (a) droplets sized between ∼ 6 – 14 μm are most efficient at direct landing over the nasopharyngeal viral infection hot-spot; and (b) targeted drug delivery via IU outperforms CU by approximately 2 orders-of-magnitude, under the two tested inhalation conditions. Also quite importantly, the improved delivery strategy, facilitated by the IU protocol, is found to be robust to small perturbations in spray direction, underlining the practical utility of this simple change in nasal spray administration protocol.
Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune mediated inflammatory diseases
Authors: Dayam Roya M. , Law Jaclyn C. , Goetgebuer Rogier L. , Chao Gary Y. C. , Abe Kento T. , Sutton Mitchell , Finkelstein Naomi , Stempak Joanne M. , Pereira Daniel , Croitoru David , Acheampong Lily , Rizwan Saima , Rymaszewski Klaudia , Milgrom Raquel , Ganatra Darshini , Batista Nathalia V. , Girard Melanie , Lau Irene , Law Ryan , Cheung Michelle W. , Rathod Bhavisha , Kitaygorodsky Julia , Samson Reuben , Hu Queenie , Hardy W. Rod , Haroon Nigil , Inman Robert D. , Piguet Vincent , Chandran Vinod , Silverberg Mark S. , Gingras Anne-Claude , Watts Tania H.
Published: January 2022

Background

Limited information is available on the impact of immunosuppressants on COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMID).

Methods

This observational cohort study examined the immunogenicity of SARS-CoV-2 mRNA vaccines in adult patients with inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, or psoriatic disease, with or without maintenance immunosuppressive therapies. Antibody and T cell responses to SARS-COV-2, including neutralization against SARS-CoV-2 variants were determined before and after 1 and 2 vaccine doses.

Results

We prospectively followed 150 subjects, 26 healthy controls, 9 IMID patients on no treatment, 44 on anti-TNF, 16 on anti-TNF with methotrexate/azathioprine (MTX/AZA), 10 on anti-IL-23, 28 on anti-IL-12/23, 9 on anti-IL-17, and 8 on MTX/AZA. Antibody and T cell responses to SARS-CoV-2 were detected in all participants, increasing from dose 1 to dose 2 and declining 3 months later, with greater attrition in IMID patients compared to healthy controls. Antibody levels and neutralization efficacy against variants of concern were substantially lower in anti-TNF treated patients than in healthy controls and were undetectable against Omicron by 3 months after dose 2.

Conclusions

Our findings support the need for a third dose of mRNA vaccine and for continued monitoring of immunity in these patient groups.

Funding

Funded by a donation from Juan and Stefania Speck and by Canadian Institutes of Health (CIHR) /COVID-Immunity Task Force (CITF) grants VR-1 172711 and VS1-175545 (T.H.W. and A.C.G); CIHR FDN-143250 (T.H.W.), GA2-177716 (V.C., A.C.G., T.W.), GA1-177703 (A.C.G.) and the CIHR rapid response network to SARS-CoV-2 variants, CoVaRR-Net (to A.C.G.).
General practitioner wellbeing during the COVID-19 pandemic: a qualitative interview study
Authors: Jefferson Laura , Heathcote Claire , Bloor Karen
Published: January 2022

Background

Workload pressures and poor job satisfaction have been reported by UK general practitioners (GPs) for some time. The COVID-19 pandemic presented new challenges, with growing international evidence of its negative impact on GPs’ mental health and wellbeing. While there has been wide commentary on this topic, UK research evidence is lacking. Developing greater understanding of these lived experiences and subgroup differences is important as doctor wellbeing may affect the sustainability of health care systems and quality of patient care.

Objectives

To explore the lived experience of UK GPs during COVID-19, and the pandemic’s impact on their psychological wellbeing.

Design and Setting

In-depth qualitative interviews, conducted remotely by telephone or video call, with NHS GPs.

Participants

GPs were sampled purposively across three career stages (early career, established and late career or retired GPs) with variation in other key demographics. A comprehensive recruitment strategy used multiple channels. Data were analysed thematically using Framework Analysis.

Results

We interviewed 40 GPs; most described generally negative sentiment and many displayed signs of psychological distress and burnout. Causes of stress and anxiety related to personal risk, workload, practice changes, public perceptions and leadership, teamworking and wider collaboration and personal challenges. GPs described facilitators of their wellbeing, including sources of support and plans to reduce clinical hours or change career path.

Conclusions

A range of factors detrimentally affected the wellbeing of GPs during the pandemic and we highlight the potential impact of this on workforce retention and quality of care. As the pandemic progresses and general practice faces continued challenges, urgent policy measures are now needed.

Strengths and limitations of this study

While there is growing international evidence base demonstrating the impact of the COVID-19 pandemic on GPs’ wellbeing and much UK media coverage, this qualitative interview study provides much-needed research evidence of UK GPs’ lived experiences and wellbeing during COVID-19.

40 GPs were sampled purposively to include GPs with different demographic and practice characteristics.

While there are no easy solutions to the problems highlighted, this research provides increased contextualised understanding of how these experiences may impact future workforce retention and the sustainability of health systems longer-term.

Sub-group differences by gender and age are reported; highlighting a potential need for further research and support targeted at specific groups.

Findings are necessarily limited to the time of data collection (Spring/Summer 2021); further tensions in general practice have since arisen, particularly regarding negative and misleading media portrayal.
SARS-CoV-2 third vaccine immune response in MS patients treated with ocrelizumab
Authors: Brill Livnat , Raposo Catarina , Rechtman Ariel , Zveik Omri , Levin Netta , Oiknine-Djian Esther , Wolf Dana G. , Vaknin-Dembinsky Adi
Published: January 2022

The introduction of a third dose vaccination along with new variants of concerns raises questions regarding serology and T-cell responses in patients with MS (pwMS) treated with B-cell depletion who develop attenuated humoral response to vaccines. The aim of this study is to longitudinally evaluate humoral and cellular response to SARS-CoV-2 mRNA vaccine in ocrelizumab-treated pwMS before and following third vaccine dose. Following the third vaccine dose, patients who are low or non-responders following initial vaccination did not increase antibody titers. In HCs and ocrelizumab-treated pwMS, cellular response decreased 6 months following initial vaccination and increased significantly after the third booster.
Mentalizing abilities mediate the impact of the low-level social cognitive processes on negative symptoms
Authors: Okruszek Ł. , Chrustowicz M. , Jarkiewicz M. , Krawczyk M. , Manera V. , Piejka A. , Schudy A. , Wiśniewska M. , Wysokiński A.
Published: January 2022

Social cognitive deficits are currently considered as one of the main predictors of clinical symptoms and functional outcome in patients with schizophrenia. Multiple studies have suggested that two-factor solution (low-level vs. high-level) best describes the structure of social cognitive processes in patients. While higher-order processes have been repeatedly linked to negative symptoms, no such association was found for lower-level processes. Thus, the aim of the current study is to examine whether the association between low-level socio-perceptual processes and symptoms in patients with schizophrenia is mediated by higher-order socio-inferential abilities. One hundred thirty-nine patients have completed basic communicative interactions processing (CID-12) and mind reading (Reading the Mind in the Eyes task) tasks. In line with our hypothesis, we have observed full mediation of the effects of basic social perception abilities on negative symptoms via mentalizing abilities in patients. This effect suggests that, similarly as in the case of positive symptoms, a hierarchical nature of social cognitive processes should be considered while investigating negative symptoms of schizophrenia.
Fifteen Days in December: Capture and Analysis of Omicron-Related Travel Restrictions
Authors: Schermerhorn Jordan , Case Alaina , Graeden Ellie , Kerr Justin , Moore Mackenzie , Robinson-Marshall Siobhan , Wallace Trae , Woodrow Emily , Katz Rebecca
Published: January 2022

Following the identification of the Omicron variant of the SARS-CoV-2 virus in late November 2021, governments worldwide took actions intended to minimize the impact of the new variant within their borders. Despite guidance from the World Health Organization advising a risk-based approach, many rapidly implemented stringent policies focused on travel restrictions. In this paper, we capture 221 national-level travel policies issued during the three weeks following publicization of the Omicron variant. We characterize policies based upon whether they target travelers from specific countries or focus more broadly on enhanced screening, and explore differences in approaches at the regional level. We find that initial reactions almost universally focused on entry bans and flight suspensions from Southern Africa, and that policies continued to target travel from these countries even after community transmission of the Omicron variant was detected elsewhere in the world. While layered testing and quarantine requirements were implemented by some countries later in this three-week period, these enhanced screening policies were rarely the first response. The timing and conditionality of quarantine and testing requirements were not coordinated between countries or regions, creating logistical complications and burdening travelers with costs. Overall, response measures were rarely tied to specific criteria or adapted to match the unique epidemiology of the new variant.

Summary box

During the initial three-week period following the discovery of the SARS-CoV-2 Omicron variant, nations rushed to implement travel restrictions - often at odds with guidance from the World Health Organization.

By sourcing and cataloging initial national-level travel restrictions worldwide, we demonstrate how the distribution of entry bans, flight suspensions, quarantine measures, vaccination requirements, and testing protocols evolved in response to emerging information during a period of uncertainty.

Countries that issued entry bans almost universally targeted the same Southern African countries and continued to do so even after widespread community transmission of the Omicron variant was reported elsewhere in the world.

Layers of testing and quarantine requirements were added later during the observation period but were rarely the initial response, with the exception of restrictions issued by countries in Africa, where leading with enhanced screening measures was more common.

Analysis of the disconnect between travel restrictions and transmission patterns that followed emergence of the Omicron variant provides a basis to inform evidence-based control measures for future virus mitigation efforts.
Static magnetic stimulation induces structural plasticity at the axon initial segment of inhibitory cortical neurons
Authors: Beros J.L. , King E.S. , Clarke D. , Rodger J. , Tang A.D
Published: January 2022

Static magnetic stimulation (SMS) is a form of non-invasive brain stimulation that can alter neural activity and induce neural plasticity that outlasts the period of stimulation. While SMS is typically delivered for short periods (e.g., 10 minutes) to alter corticospinal excitability or motor behaviours, the plasticity mechanisms that can be induced with longer periods of stimulation have not been explored. In mammalian neurons, the axon initial segment (AIS) is the site of action potential initiation and undergoes structural plasticity as a homeostatic mechanism to counteract chronic changes in neuronal activity. Therefore, we investigated whether the chronic application of SMS would induce structural AIS plasticity in cortical neurons. SMS (0.5 Tesla in intensity) was delivered to postnatally derived mouse primary cortical neurons consisting of mainly inhibitory neurons, for 6 or 48 hours beginning from 7 days in vitro (DIV7). AIS structural plasticity (length and starting distance from the soma) was quantified immediately after and 24 hours post-stimulation. Following 6 hours of stimulation, we observed an immediate decrease in median AIS length compared to control, that persisted to 24 hours post stimulation. In addition, there was a distal shift in the AIS start position relative to the soma that was only observed 24 hours after the 6-hour stimulation. Following 48 hours of stimulation, we observed an immediate shortening of AIS length and a distal shift in AIS start position relative to the soma, however only the distal shift in AIS start position persisted to 24 hours post-stimulation. Our findings provide the foundation to expand the use of SMS to more chronic applications as a method to study or promote AIS plasticity non-invasively.
African-Ancestry Associated Gene Expression Signatures and Pathways in Triple Negative Breast Cancer, a Comparison across Women of African Descent
Authors: Martini Rachel , Delpe Princesca , Chu Timothy R. , Arora Kanika , Lord Brittany , Verma Akanksha , Chen Yalei , Gebregzabher Endale , Oppong Joseph K. , Adjei Ernest K. , Jibril Aisha , Awuah Baffour , Bekele Mahteme , Abebe Engida , Kyei Ishmael , Aitpillah Frances S. , Adinku Michael O. , Ankomah Kwasi , Osei-Bonsu Ernest B. , Chitale Dhananjay , Bensenhaver Jessica M. , Nathanson Saul David , Jackson LaToya , Jiagge Evelyn , Petersen Lindsay F. , Proctor Erica , Gyan Kofi K. , Gibbs Lee , Monojlovic Zarko , Kittles Rick , White Jason , Yates Clayton , Manne Upender , Gardner Kevin , Mongan Nigel , Cheng Esther , Ginter Paula , Hoda Syed , Elemento Olivier , Robine Nicolas , Sboner Andrea , Carpten John , Newman Lisa , Davis Melissa B.
Published: January 2022

Women of sub-Saharan African ancestry have disproportionately higher incidence of aggressive, early-onset Triple Negative Breast Cancer (TNBC), and TNBC mortality across all race groups. Population-based comparative studies show racial differences in TNBC tumor biology, with higher prevalence of basal-like and Quadruple-Negative subtypes in African Americans (AA). However, most investigations relied on self-reported race (SRR) of primarily United States (US) populations. However, given that genetic admixture in AAs is extremely heterogenous, and race-correlated social determinants can translate into biological differences, the true association of African ancestry with TNBC biology and gene expression is currently unclear. To address this, we conducted RNAseq on an international cohort of AAs, west and east Africans with TNBC. Using genetic ancestry estimation in this African-enriched cohort, we identified 613 genes associated with African ancestry and more than 2200 genes associated with regional-level African ancestry. Functional enrichment and deconvolution revealed tumor-associated immune cell infiltration and activity.

STATEMENT OF SIGNIFICANCE

Using a rigorous ancestry quantification process, we show that TNBC has ancestry-associated gene expression profiles, linked to immunological landscapes, which may contribute to racial differences in clinical outcomes. This is the first study to show the definitive link to tumor immunological landscape, associated with African ancestry, using a multiethnic African-enriched cohort.
Long-term and low-level envelope C2V3 stimulation from highly diverse virus isolates leads to frequent development of broad and elite antibody neutralization in HIV-1 infected individuals
Authors: Martin Francisco , Marcelino José Maria , Palladino Claudia , Bártolo Inês , Tracana Susana , Moranguinho Inês , Gonçalves Paloma , Mateus Rita , Calado Rita , Borrego Pedro , Leitner Thomas , Clemente Sofia , Taveira Nuno
Published: January 2022

Elicitation of potent neutralizing antibodies against genetically diverse HIV-1 isolates is important for an effective HIV-1 vaccine. Some HIV-1 infected patients produce such broadly neutralizing antibodies (bNAbs). Identification of host and viral correlates of bNAb production may help develop the next generation of HIV-1 vaccines. We carried out the first detailed characterization of the neutralizing antibody response and identify viral and host factors associated with the development of bNAbs in HIV-1 infected patients from Angola, one of the oldest, more dynamic, and diverse HIV-1 epidemics in the world. Plasma samples from 322 HIV-1 infected patients were collected in 2001, 2009 and 2014. Phylogenetic analysis of C2V3C3 envelope sequences identified a diverse array of subtypes including A1, A2, B, C, D, F1, G, H, J, untypable strains, and recombinant forms which prevailed over pure subtypes. Notably, 56% of the patients developed cross, broad, or elite neutralizing responses against a reference panel of tier 2 Env-pseudoviruses far exceeding results obtained elsewhere in the world. The frequency of elite neutralizers was higher in 2014, when patients were on ART and had low viremia, than in 2009 when patients were drug naive. In drug naïve patients, broad neutralization was associated with subtype C infection, lower CD4+ T cell counts, higher age, or higher titer of C2V3C3-specific antibodies relative to patients that did not develop bNAbs. Neutralizing antibodies targeted the V3-glycan supersite in most patients but antibodies specific for the V2 apex, the CD4 binding site, the gp41 membrane-proximal external region (MPER) and unknown epitopes were also found in some patients. V3 and C3 regions were significantly less variable and less subject to positive selection in elite neutralizers compared to weak or no neutralizers suggesting an active role of bNabs directed against these regions in controlling HIV-1 replication and diversification. Hence, development of broad and elite antibody neutralization against HIV-1 requires long-term and low-level envelope V3C3 stimulation from highly diverse subtype C isolates. These results have direct implications for the design of a new generation of HIV-1 vaccines.
Enhancing the BOADICEA cancer risk prediction model to incorporate new data on RAD51C, RAD51D, BARD1, updates to tumour pathology and cancer incidences
Authors: Lee Andrew , Mavaddat Nasim , Cunningham Alex P. , Carver Tim , Archer Stephanie , Walter Fiona M. , Tischkowitz Marc , Roberts Jonathan , Usher-Smith Juliet , Simard Jacques , Schmidt Marjanka K. , Devilee Peter , Zadnik Vesna , Jürgens Hannes , Mouret-Fourme Emmanuelle , De Pauw Antoine , Rookus Matti , Mooij Thea M. , Pharoah Paul P.D. , Easton Douglas F. , Antoniou Antonis C.
Published: January 2022

Background

BOADICEA for breast cancer and the epithelial ovarian cancer (EOC) models included in the CanRisk tool (www.canrisk.org) provide future cancer risks based on rare pathogenic variants in cancer-susceptibility genes, polygenic risk scores, breast-density, questionnaire-based risk factors and family history. Here, we extend the models to include the effects of pathogenic variants in recently established breast cancer and EOC susceptibility genes, up-to-date age-specific pathology distributions and continuous risk factors.

Methods

BOADICEA was extended to further incorporate the associations of pathogenic variants in BARD1, RAD51C and RAD51D with breast cancer risk. The EOC model was extended to include the association of PALB2 pathogenic variants with EOC risk. Age-specific distributions of oestrogen-receptor-negative and triple-negative breast cancer status for pathogenic variant carriers in these genes and CHEK2 and ATM were also incorporated. A novel method to include continuous risk factors was developed, exemplified by including adult-height as continuous.

Results

BARD1, RAD51C and RAD51D explain 0.31% of the breast cancer polygenic variance. When incorporated into the multifactorial model, 34-44% of these carriers would be reclassified to the near-population and 15-22% to the high-risk categories based on the UK NICE guidelines. Including height as continuous, increased the BC relative-risk variance from 0.002 to 0.010.

Conclusions

These extensions will allow for better personalised risks for BARD1, RAD51C, RAD51D and PALB2 pathogenic variant carriers and more informed choices on screening, prevention, risk factor modification or other risk-reducing options.