bluuebunny/crossref_metadata_2025 huggingface dataset:
Operation and management of a community treatment center using telemedicine for foreign patients with mild COVID-19 symptoms
Authors: Kim Han Bit , Han Sangsoo , Shin Heejun , Lee Young Hwan , Lee Kyung Min , Kwak Jae Ryoung , Cho Young Soon , Kim Hojung , Lim Hoon , Kim Gi Woon , Eo Eunkyung , Noh Hyun
Published: December 2021

South Korean studies on coronavirus disease-2019 (COVID-19) treatment have described the use of community treatment centers (CTCs), which combine elements of the home and hospital, to isolate and treat mild COVID-19 patients. While the number of South Koreans diagnosed with COVID-19 cases has varied greatly by season, the number of confirmed cases in foreign nationals has shown no seasonality, with an average of around 25 to 30 per day. For foreign patients, accommodation arrangements and travel routes may be difficult; they may also have difficulty accessing medical care, so require careful management.

We discuss our experience in operating and managing a CTC for foreign COVID-19 patients arriving in South Korea with mild symptoms. We also propose guidelines for efficient use of resources with respect to treating these patients in CTCs.

We present the clinical findings of patients treated at the CTC between 7 October and 22 November 2020, and make some recommendations. We quarantined and treated foreign patients with mild symptoms of COVID-19 at the Ansan CTC. Discharge is determined based on clinical symptoms rather than polymerase chain reaction results. Medical and administrative staff use building A, while building B is used for isolating patients. Medical rounds are in the form of twice-daily video calls. Three kinds of foods with medication are served according to the patient's country of origin.

In total, 315 patients were admitted to the Ansan CTC between 7 October and 22 November 2020; 145 of them were discharged from the CTC and 26 were transferred to other hospitals.

To utilize medical resources efficiently during the pandemic, it is desirable to reserve CTCs exclusively for foreign patients.
Identification of FOXG1 mutations in infantile hypotonia and postnatal microcephaly
Authors: Jang Han Na , Kim Taeho , Jung Ah Young , Lee Beom Hee , Yum Mi-Sun , Ko Tae-Sung
Published: December 2021

FOXG1, located at chromosome 14q12, is critical for brain development, and patients with FOXG1 mutation exhibit developmental encephalopathy with high phenotypic variability, known as FOXG1 syndrome. Here, we report 3 cases of FOXG1 syndrome that presented with infantile hypotonia and microcephaly.

A total of 145 children with developmental delay and/or hypotonia were evaluated by whole-exome sequencing (WES) in the pediatric neurology clinic and medical genetics center at Asan Medical Center Children's Hospital, from 2017 to 2019. Each FOXG1 mutation was confirmed by Sanger sequencing. The clinical findings of each patient with FOXG1 mutation were reviewed.

WES identified de-novo, pathogenic, and heterozygous FOXG1 mutations in 3 of 145 patients in our patient cohort with developmental delay and/or hypotonia. The characteristics of brain magnetic resonance imaging (MRI) were reported as callosal anomaly, decrease in frontal volume, fornix thickening, and hypoplastic olfactory bulbs. A phenotype-genotype correlation was demonstrated as a patient with a novel missense mutation, c.761A > C (p.Tyr254Ser), in the forkhead domain had better outcome and milder brain abnormalities than the other 2 patients with truncating mutation in the Groucho binding domain site, c.958delC (p.Arg320Alafs), or N-terminal domain, c.506dup (p.Lys170GlnfsThe). Importantly, all 3 patients had hypoplastic olfactory bulbs on their brain MRI, which is a distinct and previously unrecognized feature of FOXG1 syndrome.

This is the first report of FOXG1 syndrome in a Korean population; this condition accounts for 2% (3 of 145 patients) of our patient cohort with developmental delays and/or hypotonia. Our report contributes to understanding this extremely rare genetic condition in the clinical and genetic perspectives.
Effects of evidence-based nursing combined with enhanced recovery after surgery on shoulder joint function and neurological function after arthroscopic rotator cuff injury repair
Authors: He Lu , Li Yanlin , Liao Xinyu , Wang Yang , Pu Li , Gao Fei , Wang Guoliang
Published: December 2021

To explore the effect of Enhanced Recovery After Surgery (ERAS) nursing combined with limbs training on shoulder joint range of motion and neurological function of patients with rotator cuff injury after surgery.

60 patients who underwent arthroscopic rotator cuff repair were randomly divided into experimental group and control group, with 30 cases in each group. The experimental group received ERAS nursing combined with rehabilitation training, while the control group received routine nursing. The prognostic effects of nursing care and shoulder joint range of motion between the two groups were compared.

There were differences in general indicators between the two groups (P = .001). There was no significant difference in the evaluation indexes of the two groups of patients (P > .05). The visual analog scale score and the degree of swelling of the affected limb of the experimental group were lower than those of the control group (P = .001; .001). After 1, 6, 12 weeks of treatment, the Constant-Murley, American Shoulder and Elbow Surgeons and University of California-Los Angeles scores of the experimental group were higher than those of the control group (P = .001; .001; .001). After 2, 4 weeks of treatment, the National Institutes of Health Stroke Scale scores of the experimental group were lower than those of the control group (P = .001). The self-efficacy evaluation of the experimental group was significantly better than that of the control group (P = .001); the complication rate was lower than that of the control group (P = .006).

Compared with simple postoperative nursing recovery, ERAS nursing combined with limbs training can improve the exercise capacity of the shoulder joint and the recovery of neurological function, reduce the occurrence of complications.
Effect of delayed palivizumab administration on respiratory syncytial virus infection-related hospitalisation
Authors: Kamori Akiko , Morooka Yuya , Yamamura Kenichiro , Chong Pin Fee , Kuga Noriko , Takahata Yasushi , Sagawa Koichi , Furuno Kenji
Published: December 2021

Respiratory syncytial virus (RSV) infection is an important cause of hospitalization in infants and young children. Monthly administration of palivizumab during the RSV season is effective in preventing severe infections in children with comorbidities. However, determining the onset of the RSV season for starting palivizumab is often challenging. The present study aimed to evaluate the ideal timing to start palivizumab and its effect on hospitalization in the real world.

We performed a retrospective, observational study to identify the relationship between the timing of the first dose of palivizumab administration and RSV-related hospitalization. Medical records from 2015 to 2019 were reviewed. We included patients who had indications for palivizumab as of July 1 in each year. We counted the proportion of children receiving palivizumab and the number of RSV infection-related hospitalizations each month. We also evaluated the differences in background and underlying disease between children with and without hospitalization.

A total of 498 patients were included, and 105 (21.0%) completed the first dose in July when the RSV season usually begins in Japan. Twenty-three (4.6%) patients were hospitalized for RSV infection during the observation period, with 13 (56.5%) hospitalizations before their first dose of palivizumab. The remaining 10 patients were hospitalized after receiving 1 or more doses of palivizumab. Children living with siblings and children with cyanosis originating from congenital heart disease had a higher risk of RSV with odds ratios of 5.1 (95% confidence interval 1.48-17.6, P < .01) and 3.3 (95% confidence interval 1.33-7.94, P < .01), respectively.

Delays in administering palivizumab at the beginning of the season increases the rate of RSV infection-related hospitalization. To maximize prophylactic effectiveness, administering the first dose as early as possible in the RSV season is crucial, with priority for cyanotic children or those with siblings.
Anti-EGFR monoclonal antibody plus chemotherapy for treating advanced non-small cell lung cancer
Authors: Luo Wenqing , Li Yuanqi , Ye Fei , Li Qiangming , Zhang Guoqing , Li Jindong , Li Xiangnan
Published: December 2021

Background:

The use of standard cytotoxic chemotherapy seems to have reached a “treatment plateau”. The application of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) is a new strategy for non-small-cell lung cancer (NSCLC) therapy. We aimed to comprehensively assess the efficacy and safety of anti-EGFR-mAbs plus chemotherapy as first-line therapy for advanced NSCLC.

Methods:

According to inclusion and exclusion criteria, we conducted a comprehensive literature search of electronic databases. From the included trials, information on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) was extracted.

Results:

The research showed that compared with chemotherapy alone, anti-EGFR-mAb plus chemotherapy combinations significantly improved OS (HR = 0.88, 95%CI: 0.83-0.94, P < .0001), PFS (HR = 0.89, 95%CI: 0.83-0.95, P = 0.0004) and ORR (OR = 1.39, 95%CI: 1.13-1.69, P = .001). Meta subgroup analyses manifested that the OS of patients with squamous NSCLC treated with anti-EGFR-mAb plus chemotherapy combinations was notably better than that of patients with non-squamous NSCLC treated with the same combinations (HR = 0.82, 95%CI: 0.73-0.92, P = .0005). Compared with the chemotherapy group, combination of chemotherapy and anti-EGFR mAb showed increase in incidences of severe AEs (> = grade 3) that mainly include, leukopenia (OR = 1.53, 95%CI: 1.28-1.82, P < .00001), febrile neutropenia (OR = 1.35, 95%CI: 1.06-1.71, P = .02), hypomagnesemia (OR = 5.68, 95%CI: 3.54-9.10, P < .00001), acneiform rash (OR = 35.88, 95%CI: 17.37-74.10, P < .00001), fatigue (OR = 1.24, 95%CI: 1.02-1.49, P = .03), diarrhea (OR = 1.69, 95%CI: 1.16-2.47, P = .006), and infusion-related reactions (OR = 3.78, 95%CI: 1.93-7.41, P = .0001).

Conclusion:

Adding an anti-EGFR-mAb to the standard platinum-based chemotherapy regimens used for the first-line treatment of advanced NSCLC resulted in statistically notable improvements in OS, PFS, and ORR. In particular, anti-EGFR-mAb and chemotherapy combinations achieved greater survival benefits in patients with squamous NSCLC than in those with non-squamous NSCLC. In addition, the safety profile of chemotherapy plus anti-EGFR-mAb combinations was acceptable compared to that of chemotherapy alone.
Complication rates following all-epiphyseal ACL reconstructions in skeletally immature patients
Authors: Saad Lydia , Grimard Guy , Nault Marie-Lyne
Published: December 2021

The aim was to evaluate the safety of a physeal-sparing anterior cruciate ligament reconstruction technique (ACLR), performed with Orthopediatrics (Warsaw, IN) equipment, by assessing complications.

Skeletally immature patients who underwent all-epiphyseal ACLR between 2015 and 2017 with postoperative follow-up were included in this retrospective study. Complications, demographic, clinical, surgical, and imaging data was retrieved from an urban tertiary pediatric hospital database. Physeal status, limb-length discrepancies (LLD), and angular deformities were assessed on preoperative and postoperative radiographs, growth disturbances were reported, and initial and follow-up diameters of tunnels were compared.

Nineteen ACLRs were included from 18 patients, 4 females and 14 males, with bone age at surgery of 13.3 ± 1.0 years. At a mean follow-up of 19.2 ± 10.1 months, there were no symptomatic growth disorders requiring intervention. There were: 2 (11.1%) unilateral early physeal closures, 2 (10.5%) new angular deformities (5°–10°), 4 (22.2%) LLD (1–2 cm), 1 (5.6%) contralateral ACLR, 1 (5.6%) femoral screw removal, 2 (10.5%) graft ruptures, and 1 meniscal tear (5.3%). Mean tunnel widening was 1.7 mm and 1.5 mm on the femoral and tibial side, respectively, and no massive osteolysis was recorded at the polyetheretherketone implant site.

The complication rates were comparable to those in similar studies, with no growth-related complications at 19.2 months.
Electrocupuncture combined rehabilitation therapy for upper limb spasticity after stroke
Authors: Lou Huijuan , Li Zhanxin , Pang Tingting , Zhang Xinxin , Meng Meng , Yang Kang , Zhang Hongshi , Wang Yufeng , Cong Deyu
Published: December 2021

Background:

The purpose of this study was to evaluate the effectiveness and safety of electroacupuncture combined with rehabilitation in the treatment of spasticity after stroke.

Methods:

To collect relevant literature, we will research following databases: Medicine, PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wan-Fang Database, Chongqing VIP Chinese Science and Technology Periodicals Database and China Biomedical Database; the time is from its creation to May 2021, and the language is limited to Chinese and English. In addition, we will retrieve other literature resources, including the Chinese Clinical Trial Register and conference papers. Two reviewers will independently complete the literature screen and data extraction, and quality assessment of the included studies will be independently completed by two other researchers. The primary outcomes included the Modified Ashworth scale (MAS) and the simplified Fugl-Meyer Assessment scale (SFMA). The Modified Barthel Index (MBI), the China Stroke Scale (CSS), and adverse reactions as secondary outcomes were assessed. RevMan V.5.4.1 software will be used for meta-analysis, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) will be used to assess the quality of evidence.

Results:

This systematic review will provide a high-quality synthesis to evaluate the efficacy and safety of electroacupuncture combined with rehabilitation therapy in the treatment of upper limb spasticity after stroke, providing a reference for the safe and effective treatment of upper limb spasm after stroke.

Conclusion:

This study provides evidence that electroacupuncture combined with rehabilitation therapy is effective.

Ethics and dissemination:

The protocol of the systematic review does not require ethical approval because it does not involve humans. This article will be published in peer-reviewed journals and presented at relevant conferences.

Systematic review registration:

INPLASY202160005.
Endovascular therapy for acute basilar artery occlusion caused by vertebral artery dissection
Authors: Jiang Changchun , Liu Jiahui , Zhang Jinfeng , Cui Yujuan , Yang Junfeng , Hao Fei , Fan Yu , Wei Jianqi
Published: December 2021

Rationale:

The best endovascular therapy revascularization strategies for acute ischemic stroke caused by vertebral artery dissection (VAD) are unclear. We describes a case of basilar artery (BA) occlusion caused by extracranial VAD, in which we used a stent-retriever to achieve thrombectomy in the BA through the contralateral vertebral artery (VA).

Patient concerns:

A 32-year-old male presented with a sudden-onset headache accompanied by articulation disorder, left-sided weakness, and tinnitus in the left ear.

Diagnosis:

Digital subtraction angiography showed the V1 to V2 segment dissection of the left VA and occlusion of the BA.

Interventions:

Thrombectomy was performed through the thinner right VA with three passes of the Solitaire FR device 4 × 20 mm in the BA, and angiograms showed modified treatment in cerebral ischemia 3 reperfusion of BA and left VA V4 segment still occluded.

Outcomes:

The patient had a modified Rankin Scale of 2 at 90 days, and re-established blood flow of the left VA and BA.

Lessons:

When extracranial VAD complicated with BA occlusion, choosing the clean-road path to perform a BA thrombectomy may be a fast and effective treatment strategy.
The role of p.Val444Ala variant in the ABCB11 gene and susceptibility to biliary atresia in Vietnamese patients
Authors: Van Tung Nguyen , Lien Nguyen Thi Kim , Lan Nguyen Ngoc , Mai Nguyen Thi Phuong , Yen Pham Thi Hai , Hoa Nguyen Pham Anh , Hoang Nguyen Huy
Published: December 2021

Biliary atresia (BA) is the most serious type of obstructive cholangiopathy that occurs in infants. BA can be the cause of death in children under 2 years if untreated early. However, the etiology of the disease is not known. BA is considered to be the result of the destruction of the bile duct system including the accumulation of bile acids. The bile salt export pump, a transporter protein encoded by the ABCB11 gene, plays the main role in the exportation and accumulation of bile acids. The p.Val444Ala variant in this gene is known to be associated with many cholestatic diseases. However, to date no study have been performed to evaluate the association of this variant with susceptibility to the risk of BA. In this study, we aimed to identify the frequency of p.Val444Ala variant and the risk of BA in Vietnamese patients.

The polymerase chain reaction (PCR)– restriction fragment length polymorphism method was used to determine the frequency of alleles c.1331T>C (p.Val444Ala, rs2287622) in the ABCB11 gene in 266 Vietnamese patients with BA and 150 healthy people. The gene segment containing the variant was amplified by PCR with specific primers, after that the PCR products were cut by HaeIII restriction enzyme and analyzed on agarose gel to determine the genotypes. The frequency of alleles was assessed statistically to determine the association between these alleles and the risk of disease in patients.

In our study, the frequency of alleles c.1331T>C (p.Val444Ala, rs2287622) in the ABCB11 gene was investigated the first time in the patients with BA. The results showed that CC and TC genotypes were significantly different between BA patients and healthy people (P < .01), and the C allele was associated with an increased risk of BA (odds ratio = 2.47; 95% confidence interval: 1.84–3.32; P < .01). The initial results of clinical, biochemical, and genetic analysis in our study suggested that the p.Val444Ala variant in the ABCB11 gene may be a susceptibility factor for the disease in Vietnamese patients with BA. These results provided new insights into the role of this ABCB11 variant in the pathogenesis of BA.
A program to improve the quality of dental unit water in a medical center
Authors: Chang Su-Ping , Jiang Hui-Li , Wang Yun-Cheng , Chao Hui-Chen , Lee Jen-Jyh , Chung Hui-Chun , Wang Lih-Shinn , Ding Dah-Ching
Published: December 2021

The water quality of dental unit waterlines (DUWLs) is associated with patient safety. No program for DUWL water quality improvement has been formulated since the time they were established 20 years ago. This study provides an improvement program for the quality of dental unit water. The improvement program was implemented step by step: discharge of DUWLs for 5 minutes in the morning before clinical service to flush out the water left in the pipeline overnight; weekly disinfection of the handpiece connector with 75% alcohol and replacement of the old connector when the water quality of the same dental chair unit (DCU) was continuously found to be unqualified; monthly disinfection of the water supply system and pipeline; and establishment of DCU maintenance work standards and staff education and training. From 2016 to 2018, the water quality of 18 DCUs was tested by microorganism culture. The colonies >200 colony forming unit were categorized as unqualified. This program was divided into a pre-test phase, Phase 1, a maintenance phase, and Phase 2. A Chi-square test was used to calculate the difference of unqualified water quality numbers between each phase of the improvement program. In the pre-test phase, the water quality rate (high quality number/high-quality number + low-quality number) was 58.3%. In Phase 1, the quality rate before and after the intervention was 64.8% (35/54) and 92.2% (83/90) (P < .001), respectively. After Phase 1, the quality rate reached 100%. However, the quality rate dropped to 75% during the maintenance phase. Then, we proceeded into Phase 2 of the improvement program by further monthly disinfection to DUWLs. In Phase 2, the quality rate was 62/73 (84.9%) and improved to 142/144 (98.6%) after the intervention (P < .001). The quality rate reached 100% once again and was maintained at 100% thereafter. In conclusion, the 4 steps of the improvement program improved the water quality of the DUWL, which is important for patient safety.
Coil localization assisted wedge resection for pulmonary nodules in patients with malignant history
Authors: Xu Qing-Song , Wang Tao , Cao Wei , Rong Pan-Hao
Published: December 2021

We describe the clinical efficacy of coil localization (CL) assisted video-assisted thoracoscopic surgery (VATS) wedge resection (WR) for pulmonary nodules (PNs) in patients having a history of malignancy.

In a total of 16 patients having PNs and malignant history, treatment was carried out using computed tomography (CT)-guided CL and subsequent VATS-guided WR procedures from November 2015 to December 2019. Technical success of CL, WR, and long-term outcomes was analyzed.

A total of 21 PNs were localized (1.3 PNs per patient). A 100% technical success rate was achieved in this study for CT-guided CL. Each PN was localized with 1 coil. Two and 2 patients experienced pneumothorax and hemoptysis, respectively. VATS-guided WR also achieved a 100% technical success rate. Additional lobectomy was performed in 2 patients due to the invasive adenocarcinoma. The final diagnoses of these 21 PNs were adenocarcinoma (T1N0M0, n = 8), adenocarcinoma in situ (n = 2), pre-cancerosis (n = 1), metastasis (n = 2), and benign (n = 8). All patients underwent CT follow-up for 6 to 48 months. All patients were alive during the follow-up. The cumulative 6-, 12, and 24-month disease-free survival rates were 100%, 92.9%, and 47.3%, respectively. The median disease-free survival was 27.9 months.

Pre-operative CT-guided CL can be safely and conveniently used to facilitate a high success rate of VATS-guided WR for PNs in patients with a malignant history. Among the PNs in patients with malignant history, primary lung cancer also occupied approximately half of the PNs.
Can older patients adopt and maintain a ketogenic diet? An observational study in support of clinical trials in older patients
Authors: Almodallal Yahya , Cook Kathryn , Lammert Lisa M. , Lee Minji , Le-Rademacher Jennifer G. , Jatoi Aminah
Published: December 2021

Ketogenic diets appear promising for obesity, diabetes, cancer, and other illnesses. Because older patients are more likely to contend with such illnesses and because of a paucity of dietary outcomes among these patients, we examined ketogenic diets in older patients.

This multisite study focused on patients (≥65 years of age) on a ketogenic diet. Medical records were identified with the keywords “keto,” “ketogenic,” and “Atkins.” Records were reviewed in detail with extraction of direct quotations to substantiate observations.

We report on 200 consecutive patients with a median age of 70 years. Reasons for diet included weight loss, diabetes, and cancer; the majority remained on the diet for >1 month. In 134 (67%: 95% confidence interval: 60, 73%), the ketogenic diet appeared beneficial: 93 of 117 (79%) who sought weight loss lost weight (“She has lost 15 pounds and plans to lose another 8”); 36 of 67 (54%) who sought glucose control appeared to achieve the latter (“He has gone on a ketogenic diet and has been able to bring his sugars down significantly”); and 5 of 8 (63%) who sought improved cancer outcomes appeared to derive them (“He attributes part of the control of his cancer and increased QOL to adopting the keto for cancer diet”). Adverse events occurred in 30 patients (15%): dyslipidemia (n = 14), constipation (n = 9), sub-therapeutic international normalized ratio (n = 3), pancreatitis (n = 2), diarrhea (n = 1), and fatigue (n = 1).

Trials that test ketogenic diets for a variety of illnesses should enroll older adults.
Persisting Chemosensory Impairments in 366 Healthcare Workers Following COVID-19: An 11-Month Follow-up
Authors: Bussiere Nicholas , Mei Jie , Levesque-Boissonneault Cindy , Blais Mathieu , Carazo Sara , Gros-Louis Francois , Laforce Robert , De Serres Gaston , Dupre Nicolas , Frasnelli Johannes
Published: December 2021

Background and Objectives

Olfactory and gustatory dysfunctions (OD, GD) are prevalent symptoms following COVID-19 and persist in 6%-44% of individuals in the first months after the infection. As only few reports have described their prognosis more than 6 months later, the main objective of this study was to assess the prevalence of OD and GD 11 months after COVID-19. We also aimed to determine test-retest reliability of subjective chemosensory ratings for the follow-up of chemosensory sensitivity, as this measure is often used for remote follow-up.

Methods

Inclusion criteria included a PCR-confirmed SARS-CoV-2 infection; exclusion criteria were the presence of other respiratory infections and chronic sinusitis. To assess whether OD and GD had changed compared to pre-pandemic levels, we designed an observational study and distributed an online questionnaire assessing quantitative chemosensory function to healthcare workers 5 and 11 months after COVID-19. Specifically, we assessed olfaction, gustation, and trigeminal sensitivity (10-point visual analog scale) and function (4-point Likert scale) separately. We further assessed clinically relevant OD using the Chemosensory Perception Test, a psychophysical test designed to provide a reliable remote olfactory evaluation. Qualitative chemosensory dysfunction was also assessed.

Results

We included a total of 366 participants (mean age of 44.8 years old (SD: 11.7)). They completed the last online questionnaire 10.6 months (SD: 0.7) after the onset of COVID-19 symptoms. Of all participants, 307 (83.9%) and 301 (82.2%) individuals retrospectively reported lower olfactory or gustatory sensitivity during the acute phase of COVID-19. Eleven months later, 184 (50.3%) and 163 (44.5%) indicated reduced chemosensory sensitivity, 32.2% reported impairment of olfactory function while 24.9% exhibited clinically relevant OD. Three variables predicted OD at follow-up, namely chest pain and GD during COVID-19 and presence of phantosmia at 5 months. Olfactory sensitivity ratings had a high test-retest reliability (intraclass correlation coefficient: 0.818 (95% CI: 0.760 - 0.860))

Discussion

This study suggests that chemosensory dysfunctions persist in a third of COVID-19 patients 11 months after COVID-19. Subjective measures have a high test-retest reliability and thus can be used to monitor post-COVID-19 OD. OD appears to be a common long-term symptom of COVID-19 important to consider when treating patients.
Transmission of SARS-CoV-2 among children and staff in German daycare centers: results from the COALA study
Authors: Loss Julika , Wurm Juliane , Varnaccia Gianni , Schienkiewitz Anja , Iwanowski Helena , Loer Anne-Kathrin Mareike , Allen Jennifer , Wess Barbara , Rosario Angelika Schaffrath , Damerow Stefan , Kuttig Tim , Perlitz Hanna , Hornbacher Anselm , Finkel Bianca , Krause Carolin , Wormsbächer Jan , Sandoni Anna , Kubisch Ulrike , Eggers Kiara , Nitsche Andreas , Radonic Aleksandar , Trappe Kathrin , Drechsel Oliver , Klaper Kathleen , Franke Andrea , Hüther Antje , Buchholz Udo , Haas Walter , Wieler Lothar H. , Jordan Susanne
Published: December 2021

Background

Whereas the majority of children under 6 years of age attend daycare centers in Germany, evidence on the role of daycare centers in the transmission of SARS-CoV-2 is scarce.

Aims

This study aims to investigate the transmission risk in daycare centers among children and staff and the spread of infections to associated households.

Methods

30 daycare groups with at least one recent laboratory-confirmed SARS-CoV-2 case (child or staff) were enrolled in the study (10/2020-06/2021). Close contacts within the daycare group and households were examined over a 12-day period (repeated SARS-CoV-2 PCR tests, genetic sequencing of viruses, documentation of symptoms). Households, local health authorities and daycare staff were interviewed to gain comprehensive information on each outbreak. We determined primary cases for all daycare groups.

Results

The number of secondary cases varied considerably between daycare groups. The pooled secondary attack rate (SAR) across all 30 daycare centers was 9.6%. The SAR tended to be higher in daycare centers in which the Alpha variant of the virus was detected (15.9% vs. 5.1% with evidence of wild type). The SAR in households was 53.3%. Exposed children were less likely to get infected with SARS-CoV-2 in daycare centers, compared to adults (7.7% vs. 15.5%).

Conclusion

Containment measures in daycare programs are critical and become increasingly important with highly transmissible new variants to reduce SARS-CoV-2 transmission, especially to avoid spread to associated households. Virus variants may modify transmission dynamics in daycare programs.
SARS-CoV-2 seroprevalence in Kaduna State, Nigeria during October/November 2021, following three waves of infection and immediately prior to detection of the Omicron variant
Authors: Chechet Gloria D. , Kwaga Jacob K.P. , Yahaya Joseph , MacLeod Annette , Adamson Walt E.
Published: December 2021

Nigeria is the most populated country in Africa with an estimated ∼213 million inhabitants. As of November 2021 there have been three waves of SARS-CoV-2 infection in Nigeria but there has been only one seroprevalence survey conducted to assess the proportion of a population that have been infected, which was performed in December 2020 after the first wave of infection. To provide an update on seroprevalence in Nigeria, we conducted survey at one urban site (n=400) and one rural site (n=402) in Kaduna State, Nigeria during October and November 2021 following the third wave of infection. Seroprevalence for the urban and rural sites was 42.5% and 53.5% respectively (mean 48.0%). Symptoms associated with seropositivity were identified for each site. The overall seroprevalence among unvaccinated individuals was 45.4%. The data indicates an infection rate in Kaduna State at least 387 times greater than that derived from cases confirmed by PCR. Extrapolating to the whole of Nigeria, it would suggest there has been at least 96.7 million infections (compared to 206,138 confirmed cases at the time of surveillance). The work presented here will inform public health policy and deployment strategies for testing, treatment, and vaccination in Nigeria, and provide a baseline for SARS-CoV-2 seroprevalence in Nigeria immediately prior to the spread of the Omicron variant.
Antibody therapy reverses biological signatures of COVID-19 progression
Authors: Maher M. Cyrus , Soriaga Leah B. , Gupta Anil , di Iulio Julia , Ledoux Sarah , Smithey Megan J. , Cathcart Andrea L. , McKusick Kathleen , Sun David , Aldinger Melissa , Alexander Elizabeth , Purcell Lisa , Ding Xiao , Peppercorn Amanda , Austin Daren , Mogalian Erik , Yeh Wendy W. , Shapiro Adrienne E. , Corti Davide , Virgin Herbert W. , Pang Phillip S. , Telenti Amalio
Published: December 2021

Understanding who is at risk of progression to severe COVID-19 is key to effective treatment. We studied correlates of disease severity in the COMET-ICE clinical trial that randomized 1:1 to placebo or to sotrovimab, a monoclonal antibody for the treatment of SARS-CoV-2 infection. Several laboratory parameters identified study participants at greater risk of severe disease, including a high neutrophil-lymphocyte ratio (NLR), a negative SARS-CoV-2 serologic test and whole blood transcriptome profiles. Sotrovimab treatment in these groups was associated with normalization of NLR and the transcriptomic profile, and with a decrease of viral RNA in nasopharyngeal samples. Transcriptomics provided the most sensitive detection of participants who would go on to be hospitalized or die. To facilitate timely measurement, we identified a 10-gene signature with similar predictive accuracy. In summary, we identified markers of risk for disease progression and demonstrated that normalization of these parameters occurs with antibody treatment of established infection.
Genome-wide association study of Alzheimer’s disease brain imaging biomarkers and neuropsychological phenotypes in the EMIF-AD Multimodal Biomarker Discovery dataset
Authors: Homann Jan , Osburg Tim , Ohlei Olena , Dobricic Valerija , Deecke Laura , Bos Isabelle , Vandenberghe Rik , Gabel Silvy , Scheltens Philip , Teunissen Charlotte E. , Engelborghs Sebastiaan , Frisoni Giovanni , Blin Olivier , Richardson Jill C. , Bordet Regis , Lleó Alberto , Alcolea Daniel , Popp Julius , Clark Christopher , Peyratout Gwendoline , Martinez-Lage Pablo , Tainta Mikel , Dobson Richard J. B. , Legido-Quigley Cristina , Sleegers Kristel , Van Broeckhoven Christine , Wittig Michael , Franke Andre , Lill Christina M. , Blennow Kaj , Zetterberg Henrik , Lovestone Simon , Streffer Johannes , ten Kate Mara , Vos Stephanie J. B. , Barkhof Frederik , Visser Pieter Jelle , Bertram Lars
Published: December 2021

Alzheimer’s disease (AD) is the most frequent neurodegenerative disease with an increasing prevalence in industrialized, ageing populations. AD susceptibility has an established genetic basis which has been the focus of a large number of genome-wide association studies (GWAS) published over the last decade. Most of these GWAS used dichotomized clinical diagnostic status, i.e. case vs. control classification, as outcome phenotypes, without the use of biomarkers. An alternative and potentially more powerful study design is afforded by using quantitative AD-related phenotypes as GWAS outcome traits, an analysis paradigm that we followed in this work. Specifically, we utilized genotype and phenotype data from n=931 individuals collected under the auspices of the European Medical Information Framework for Alzheimer’s Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study to perform a total of 19 separate GWAS analyses. As outcomes we used five magnetic resonance imaging (MRI) traits and seven cognitive performance traits. For the latter, longitudinal data from at least two timepoints were available in addition to cross-sectional assessments at baseline. Our GWAS analyses revealed several genome-wide significant associations for the neuropsychological performance measures, in particular those assayed longitudinally. Among the most noteworthy signals were associations in or near EHBP1 (EH domain binding protein 1; on chromosome 2p15) and CEP112 (centrosomal protein 112; 17q24.1) with delayed recall in a memory performance test. On the X chromosome, which is often excluded in other GWAS, we identified a genome-wide significant signal near IL1RAPL1 (interleukin 1 receptor accessory protein like 1; Xp21.3). While polygenic score (PGS) analyses showed the expected strong associations with SNPs highlighted in relevant previous GWAS on hippocampal volume and cognitive function, they did not show noteworthy associations with recent AD risk GWAS findings. In summary, our study highlights the power of using quantitative endophenotypes as outcome traits in AD-related GWAS analyses and nominates several new loci not previously implicated in cognitive decline.
Humoral Immunogenicity of Three COVID-19 mRNA Vaccine Doses in Patients with Inflammatory Bowel Disease
Authors: Schell Trevor L. , Knutson Keith L. , Saha Sumona , Wald Arnold , Phan Hiep S , Almasry Mazen , Chun Kelly , Grimes Ian , Lutz Megan , Hayney Mary S. , Farraye Francis A. , Caldera Freddy
Published: December 2021

Herein, we evaluated the humoral immunogenicity of a third COVID-19 mRNA vaccine dose in patients with IBD. All patients were seropositive and had higher antibody concentrations after the third dose than after completion of the two-dose primary series.
Disease severity related to VOC dominance in unvaccinated SARS-CoV-2 positive adults without risk factors in Sweden
Authors: Wahlström Erik , Bruce Daniel , Bennet Bark Anna M , Walther Sten , Hanberger Håkan , Strålin Kristoffer
Published: December 2021

Although the emerging SARS-CoV-2 variants of concern (VOC) have shown increasing transmissibility, their role for causing severe disease has not been fully clarified. Here, we studied changes in rates of hospitalisation and severe illness (subjection to high-flow nasal oxygen or admission to an intensive care unit during hospital stay) among all (n=685 891) unvaccinated SARS-CoV-2 positive adults without risk factors in Sweden from November 2020 to September 2021.

After adjustment for age, sex, and socio-economic factors, and with November 2020 (non-VOC period) as reference, the odds ratios (OR) for hospitalisation were 1.6-1.7 in March-May 2021 (Alpha VOC dominance) and 2.4-3.0 in June-September 2021 (Delta VOC dominance), and the ORs for severe illness were 1.8-2.1 in March-May 2021 and 3.1-4.7 in June-September 2021. This study shows that unvaccinated adults without risk factors, have had a gradually increased risk for hospital admission and severe illness when infected with the Alpha and Delta VOCs, respectively.
Controlling the worldwide chaotic spreading of COVID-19 through vaccinations
Authors: Zheng Hua , Bonasera Aldo
Published: December 2021

The striking differences and similarities between the ‘Spanish-flu’ of 1918 and the Coronavirus disease of 2019 (COVID-19) are analyzed. Progress in medicine and technology and in particular the availability of vaccines has decreased the death probability from about 2% for the Spanish-flu, to about 10−4 in the UK and 10−3 in Italy, USA, Canada, San Marino and other countries for COVID-19. The logistic map reproduces most features of the disease and may be of guidance for predictions and future steps to be taken in order to contrast the virus. We estimate 6.4 × 107 deceases worldwide without the vaccines, this value decreases to 2.4 × 107 with the current vaccination rate. In November 2021, the number of deceased worldwide was 5.1 × 106. To reduce the fatalities further, it is imperative to increase the vaccination rate worldwide to at least 120 millions/day and the AstraZeneca vaccine due to its efficacity and cost is a possible route to accomplish this.
Vascular burden and cognition: Mediating roles of neurodegeneration and amyloid-PET
Authors: Ottoy Julie , Ozzoude Miracle , Zukotynski Katherine , Adamo Sabrina , Scott Christopher , Gaudet Vincent , Ramirez Joel , Swardfager Walter , Cogo-Moreira Hugo , Lam Benjamin , Bhan Aparna , Mojiri Parisa , Kang Min Su , Rabin Jennifer S. , Kiss Alex , Strother Stephen , Bocti Christian , Borrie Michael , Chertkow Howard , Frayne Richard , Hsiung Robin , Laforce Robert , Noseworthy Michael D. , Prato Frank S. , Sahlas Demetrios J. , Smith Eric E. , Kuo Phillip H. , Sossi Vesna , Thiel Alexander , Soucy Jean-Paul , Tardif Jean-Claude , Black Sandra E. , Goubran Maged ,   Medical Imaging Trials Network of Canada (MITNEC) and Alzheimer’s Disease Neuroimaging Initiative
Published: December 2021

INTRODUCTION

It remains unclear to which extent vascular burden promotes neurodegeneration and cognitive dysfunction in a cohort spanning low-to-severe small vessel disease (SVD) and amyloid-beta pathology.

METHODS

In 120 subjects, we investigated 1) whether vascular burden, quantified as total or lobar white matter hyperintensity (WMH) volumes, is associated with different cognitive domains; and 2) whether the total WMH effect on cognition is mediated by amyloid (18F-AV45-PET), glucose metabolism (18F-FDG-PET), and/or cortical atrophy.

RESULTS

Increased total WMH volume was associated with poorer performance in all cognitive domains tested, with the strongest effects observed for semantic fluency. These relationships were mediated mainly through cortical atrophy, particularly in the temporal lobe, and to a lesser extent through amyloid and metabolism. WMH volumes differentially impacted cognition depending on lobar location and amyloid status.

DISCUSSION

Our study suggests mainly an amyloid-independent pathway in which vascular burden affects cognitive impairment through temporal lobe atrophy.
PDGRFA-mutant gastrointestinal stromal tumours (GISTs) in Eastern England: clinicopathological features and outcomes of 50 patients diagnosed between 2008-2021
Authors: Favara David M , Wong Han , Harrington Jennifer , Giger Olivier , Bulusu V Ramesh
Published: December 2021

Background

PDGRFA-mutant gastrointestinal tumours (GISTs) comprise approximately 10% of GISTs and are mostly gastric. Targeted therapies against these tumours have historically been limited by tyrosine kinase inhibitor (TKI)-resistance. We reviewed the characteristics and outcome of all PDGRFA-mutant patients seen at our centre over the last 13 years.

Methods

All PDGRFA-mutant patients seen at the Cambridge University Hospitals NHS Foundation Trust GIST clinic from July 2008-July 2021 were retrospectively reviewed and followed up.

Results

50 PDGRFA-mutant GIST patients were diagnosed during the 13-year period. 60% were male. Median tumour size was 5 cm and the majority were epithelioid (44%) or mixed (36%) type. Commonest primary location was the gastric body (52%). In non-metastatic patients the low-risk modified AFIP risk group was the most common (65.2%). PDGFRA exon 18 (86%) were the most common PDGFRA mutations, most being imatinib resistant. None harboured a KIT mutation. 38% of cases had high KIT expression (immunohistochemistry), whilst 48% had patchy expression and 14% were negative. Most were positive for DOG1 (94%). CD34 was highly expressed in 48% of cases. 13% developed metastases during the 13-year follow-up period: liver (80%) being the commonest site. 76% of all patients underwent radical resection. 14% received TKI therapy. After a median follow-up of 55.1 months, 82% remained alive: 6 patients died from metastatic GIST; 3 from other causes. Median time to metastatic disease was 30.1 months, and median time from metastatic diagnosis to death was 18.5 months. Patients who presented with metastatic disease had the poorest survival outcome (p=0.001)

Conclusion

To date this is the largest single-centre European PDGRFA-mutant GIST cohort. Results highlight the generally indolent nature of PDGRFA-mutant disease (contrasted to the poor outcome of those who present with metastatic disease), male and gastric preponderance (unlike KIT-mutant GISTs), and variable KIT expression.

Highlights

Largest single-centre European PDGFRA-mutant GIST series (n=50) to date

Results confirm the relative indolent nature of non-metastatic PDGFRA-mutant GISTs

PDGFRA-mutant GISTs had variable levels of KIT protein expression (immunohistochemistry) despite being KIT-wild type.

In contrast to KIT-mutant GISTs, PDGFRA-mutant GISTs were more common in males and less frequent in parts of the stomach where KIT-mutant GISTS occur.

A minority of patients received TKI therapy. One patient with metastatic imatinib-resistant PDGFRA-mutant GIST had a 6 year response to imatinib.
The Canadian COVID-19 Experiences Project: Design and Protocol
Authors: Hall Peter A. , Fong Geoffrey T. , Hitchman Sara C. , Quah Anne C.K. , Agar Thomas , Meng Gang , Ayaz Hasan , Dore Bruce P. , Sakib Mohammad N. , Hudson Anna , Boudreau Christian
Published: December 2021

Introduction

Vaccine hesitancy and inconsistent mitigation behavior performance have been significant challenges throughout the COVID-19 pandemic. In Canada, despite relatively high vaccine availability and uptake, willingness to accept booster shots and maintain mitigation behaviors in the post-acute phase of COVID-19 remain uncertain. The aim of the Canadian COVID-19 Experiences Project (CCEP) is two-fold: 1) to identify social-cognitive and neurocognitive correlates of vaccine hesitancy and mitigation behaviors, and 2) to identify optimal communication strategies to promote vaccination and mitigation behaviors into the post-acute phase of the pandemic.

Methods and analyses

The CCEP is comprised of two components: a conventional population survey (Study 1) and a functionally interconnected laboratory study (Study 2). Study 1 will involve 3 waves of data collection. Wave 1, completed between 28 September and 21 October, 2021, recruited 1,958 vaccine-hesitant (49.8%) and fully vaccinated (50.2%) adults using quota sampling to ensure maximum statistical power. Measures included a variety of social cognitive (e.g., beliefs, intentions) and neurocognitive (e.g., delay discounting) measures, followed by an opportunity to view and rate a set of professionally produced COVID-19 public service announcement (PSA) videos for perceived efficacy. Study 2 employs the same survey items and PSAs but coupled with lab-based eye tracking and functional brain imaging to directly quantify neural indicators of attention capture and self-reflection in a smaller community sample. In the final phase of the project, subjective impressions and neural indicators of PSA efficacy will be compared and used to inform recommendations for construction of COVID-19 PSAs into the post-acute phase of the pandemic.

Ethics and dissemination

The CCEP has received ethical review and approval by the University of Waterloo Office of Research Ethics. Findings will be disseminated through peer-reviewed publications and presentations at scientific meetings.
Considering variance in pollinator responses to stressors can reveal potential for resilience
Authors: Cabirol Amélie , Gómez-Moracho Tamara , Monchanin Coline , Pasquaretta Cristian , Lihoreau Mathieu
Published: December 2021

Environmental stressors have sublethal consequences on animals, often affecting the mean of phenotypic traits in a population. However, potential effects on variance are poorly understood. Since phenotypic variance is the basis for adaptation, any influence of stressors may have important implications for population resilience.

Here we explored this possibility in insect pollinators by analysing raw datasets from 24 studies (6,913 bees) in which individuals were first exposed to stressors and then tested for cognitive tasks.

While all types of stressors decreased the mean cognitive performance of bees, their effect on variance was complex. Focusing on 15 pesticide studies, we found that the dose and the mode of exposure to stressors were critical. At low pesticide doses, cognitive variance decreased following chronic exposures but not for acute exposures. Acute exposure to low doses thus seems less damaging at the population level. In all cases however, the variance decreased with increasing doses.

Policy implications. Current guidelines for the authorization of plant protection products on the European market prioritize acute over chronic toxicity assessments on non-target organisms. By overlooking the consequences of a chronic exposure, regulatory authorities may register new products that are harmful to bee populations. Our findings thus call for more research on stress-induced phenotypic variance and its incorporation to policy guidelines to help identify levels and modes of exposure animals can cope with.