bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategies to improve HIV care outcomes for people with HIV who are out of care
Authors: Higa Darrel H. , Crepaz Nicole , Mullins Mary M. , Adegbite-Johnson Adebukola , Gunn Jayleen K.L. , Denard Christa , Mizuno Yuko
Published: January 2022

Objective:

The aim of this study was to evaluate the effectiveness of five intervention strategies: patient navigation, appointment help/alerts, psychosocial support, transportation/appointment accompaniment, and data-to-care on HIV care outcomes among persons with HIV (PWH) who are out of care (OOC).

Design:

A systematic review with meta-analysis.

Methods:

We searched CDC's Prevention Research Synthesis (PRS) Project's cumulative HIV database to identify intervention studies conducted in the U.S., published between 2000 and 2020 that included comparisons between groups or prepost, and reported at least one relevant outcome (i.e. re-engagement or retention in HIV care, and viral suppression). Effect sizes were meta-analyzed using random-effect models to assess intervention effectiveness.

Results:

Thirty-nine studies reporting on 42 unique interventions met the inclusion criteria. Overall, intervention strategies are effective in improving re-engagement in care [odds ratio (OR) = 1.79;95% confidence interval (95% CI): 1.36–2.36, k = 14], retention in care (OR = 2.01; 95% CI: 1.64–2.64, k = 22), and viral suppression (OR = 2.50;95% CI: 1.87–3.34, k = 27). Patient navigation, appointment help/alerts, psychosocial support, and transportation/appointment accompaniment improved all three HIV care outcomes. Data-to-care improved re-engagement and retention but had insufficient evidence for viral suppression.

Conclusion:

Several strategies are effective for improving HIV care outcomes among PWH who are OOC. More work is still needed for consistent definitions of OOC and HIV care outcomes, better reporting of intervention and cost data, and identifying how best to implement and scale-up effective strategies to engage and retain OOC PWH in care and reach the ending the HIV epidemic goals.
Long-term effects of evolocumab in participants with HIV and dyslipidemia: results from the open-label extension period
Authors: Boccara Franck , Caramelli Bruno , Calmy Alexandra , Kumar Princy , López J. Antonio G. , Bray Sarah , Cyrille Marcoli , Rosenson Robert S.
Published: January 2022

Objectives:

People with HIV (PWH) are at an increased risk of atherosclerotic cardiovascular disease. Suboptimal responses to statin therapy in PWH may result from antiretroviral therapies (ARTs). This open-label extension study aimed to evaluate the long-term safety and efficacy of evolocumab up to 52 weeks in PWH.

Design:

This final analysis of a multinational, placebo-controlled, double-blind, randomized phase 3 trial evaluated the effect of monthly subcutaneous evolocumab 420 mg on low-density lipoprotein cholesterol (LDL-C) during the open-label period (OLP) following 24 weeks of double-blind period in PWH with hypercholesterolemia/mixed dyslipidemia. All participants enrolled had elevated LDL-C or nonhigh-density lipoprotein cholesterol (non-HDL-C) and were on stable maximally tolerated statin and stable ART.

Methods:

Efficacy was assessed by percentage change from baseline in LDL–C, triglycerides, and atherogenic lipoproteins. Treatment-emergent adverse events (TEAEs) were examined.

Results:

Of the 467 participants randomized in the double-blind period, 451 (96.6%) received at least one dose of evolocumab during the OLP (mean age of 56.4 years, 82.5% male, mean duration with HIV of 17.4 years). By the end of the 52-week OLP, the overall mean (SD) percentage change in LDL-C from baseline was −57.8% (22.8%). Evolocumab also reduced triglycerides, atherogenic lipid parameters (non-HDL-C, apolipoprotein B, total cholesterol, very-low-density lipoprotein cholesterol, and lipoprotein[a]), and increased HDL-C. TEAEs were similar between placebo and evolocumab during the OLP.

Conclusion:

Long-term administration of evolocumab lowered LDL-C and non-HDL-C, allowing more PWH to achieve recommended lipid goals with no serious adverse events.

Trail Registration:

NCT02833844

Video abstract:

http://links.lww.com/QAD/C441
Estimation of Contrast Agent Concentration in DCE-MRI Using 2 Flip Angles
Authors: Bharadwaj Das Ayesha , Tranos James Andrew , Zhang Jin , Zaim Wadghiri Youssef , Kim Sungheon Gene
Published: January 2022

Purpose

The aim of this study was to investigate the feasibility of using 2 flip angles (FAs) with an ultrashort echo time during dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) for estimation of plasma gadolinium (Gd) concentration without using a precontrast longitudinal relaxation time T1
(T10
) measurement.

Methods

T1
-weighted DCE-MRI experiments were carried out with C57BL/6J mice using the scan protocol with 2 FAs over 3 sequential segments during 1 scan. The data with 2 FAs were used to estimate T10
(T1T
) during conversion of a time-intensity curve to the time-concentration curve. Three dosages of gadolinium-based contrast agent were used to achieve a wide range of variability in Gd concentrations when measured at 10 minutes postinjection: 0.05 mmol/kg (n = 6), 0.1 mmol/kg (n = 11), and 0.15 mmol/kg (n = 7). For comparison, the signal-to-concentration conversion was also conducted using the T10
measured from the precontrast scan (T1M
) as well as a constant T10
(2.1 seconds) from the literature (T1C
). The Gd concentrations ([Gd]) estimated using DCE-MRI data for the time of retro-orbital blood collection ([Gd]
T1T
, [Gd]
T1M
, and [Gd]
T1C
, respectively) were compared against the [Gd] of the blood samples measured by inductively coupled plasma mass spectrometry ([Gd]
MS
). In addition, contrast kinetic model analysis was conducted on mice with GL261 brain tumors (n = 5) using the 3 different methods for T10
.

Results

T1T
strongly correlated with T1M
(r = 0.81). [Gd]
T1M
and [Gd]
T1T
were significantly different from [Gd]
T1C
. [Gd]
T1M
and [Gd]
T1T
were in good agreement with [Gd]
MS
with strong correlations (mean percentage error ± standard deviation) of r = 0.70 (16% ± 56%) and r = 0.85 (15% ± 44%), respectively. In contrast, [Gd]
T1C
had a weak correlation of r = 0.52 with larger errors of 33% ± 24%. The contrast kinetic model parameters of GL261 brain tumors using T1T
were not significantly different from those using T1M
.

Conclusions

This study substantiates the feasibility of using the 2-FA approach during DCE-MRI scan to estimate [Gd] in the plasma without using an extra scan to perform precontrast T1
measurements.
Photon-Counting Detector CT-Based Vascular Calcium Removal Algorithm
Authors: Allmendinger Thomas , Nowak Tristan , Flohr Thomas , Klotz Ernst , Hagenauer Junia , Alkadhi Hatem , Schmidt Bernhard
Published: January 2022

Objectives

The diagnostic performance of coronary computed tomography angiography is known to be negatively affected by the presence of severely calcified plaques in the coronary arteries. In this article, the performance of a novel image reconstruction algorithm (PureLumen) based on spectral CT data of a first-generation dual-source photon-counting detector computed tomography (PCD-CT) system was assessed in a phantom study. PureLumen tries to remove only the calcified contributions from the image while leaving the rest unmodified.

Materials and Methods

The study uses 2 iodine contrast filled vessel phantoms (diameter 4 mm) filled with different concentrations of iodine and equipped with calcified stenosis inserts. Each phantom features 2 separate calcified lesions of 25% and 50% percentage diameter stenosis (PDS) size. The vessel phantoms were mounted inside an anthropomorphic thorax phantom attached to an artificial motion device, simulating realistic cardiac motion at heart rates between 50 beats per minute and 100 beats per minute. Acquisitions were performed using a prospectively electrocardiogram triggered dual-source sequence mode on a PCD-CT system (NAEOTOM Alpha, Siemens Healthineers). Images were reconstructed at 80% of the RR interval with virtual monoenergetic images (Mono) and with additional calcium-removal (PureLumen), both at 65 keV. PureLumen is based on a spectral base material decomposition into iodine and calcium, which aims to reconstruct images without calcium contributions, while leaving all other material contribution unchanged. Stenosis grade was assessed individually for each vessel insert in all reconstructed image series by 2 readers.

Results

The measured median PDS values for the 50% lesion were 56.0% (52.0%, 57.0%) for the Mono case and 50.0% (48.5%, 51.0%) for PureLumen. The 25% lesion median PDS values were 36.0% (29.5%, 39.5%) for Mono and 31.5% (30.5%, 34.0%) for PureLumen. Both lesion sizes demonstrate a significant difference between Mono and PureLumen in their result (P < 0.05) with PureLumen median values being closer to the actual true stenosis size for the 50% and 25% lesion. A visual assessment of the image quality depending on the heart rate yielded good image quality up to a heart rate of 80 beats per minute in the PureLumen case.

Conclusions

This phantom study shows that a novel calcium-removal image reconstruction algorithm (PureLumen) using a first-generation dual-source PCD-CT effectively decreases blooming artifacts caused by heavily calcified plaques and improves image interpretability. It also shows that PureLumen retains its performance in the presence of motion with simulated heart rates up to 80 beats per minute. Future in vivo clinical studies are needed to confirm the benefits of this type of reconstruction in terms of coronary computed tomography angiography quality and accuracy.
Intravenous Tumor Thrombus From Papillary Carcinoma of Thyroid Demonstrated by 18F-FDG PET/CT
Authors: Wang Yu , Jiang Lisha , Zhang Xinyue , Xu Yangmengyuan , Liu Bin
Published: January 2022

A 24-year-old man with papillary thyroid carcinoma underwent 131I ablation after thyroidectomy. On posttherapy whole-body scintigraphy, only the remnant thyroid was visualized. In view of elevated unstimulated thyroglobulin level 7 months after 131I ablation, 18F-FDG PET/CT scan was ordered for further evaluation. On PET/CT images, a large filling defect from the dilated left brachiocephalic vein to superior vena cava was noted corresponding with high FDG uptake. It was considered as a malignant thrombus.
Increased Accumulation of 18F-FDG Incidentally Observed in Hyperacute Cerebral Infarction
Authors: Sotome Wataru , Ito Yoshiaki , Higuchi Nobuya , Asami Yuta , Satomi Nao
Published: January 2022

A 75-year-old man with lung cancer undertook an 18F-FDG PET/CT for staging. He presented neurological symptoms immediately after the 30-minute scan. An emergent MRI study revealed hyperacute cerebral infarction with occlusion of a left MCA branch. At PET/CT, an increased 18F-FDG uptake was observed in the corresponding areas of infarction. In literature, acceleration of compensatory anaerobic glycolysis has been proposed as 1 of the causes of increased uptake in the penumbra of acute cerebral infarction, and a similar process was hypothesized in this case. In addition, a decreased 18F-FDG uptake in the ipsilateral thalamus was noted on the PET/CT images.
Foreign Body Granuloma Masquerading as Remnant Lymphoma on 18F-FDG PET/CT
Authors: Zhang Wenjie , Sun Hongbao , Shen Guohua
Published: January 2022

A 54-year-old man complained of a growing nodule in the left upper arm, which was diagnosed as diffuse large B-cell lymphoma by postsurgical pathology. For baseline assessment, FDG PET/CT revealed intense uptake in the left upper arm, in addition to FDG-avid pleura lesions and regional, axillary, cervical, and mediastinal lymph nodes. After chemotherapy, the restaging scan showed complete remission of most involved lesions except for increased activity in the prior surgical site. The patient eventually underwent surgical resection again, and the diagnosis was confirmed as foreign body granuloma.
Osteoblastoma of the Rib Mimicking Lymphomatous Involvement on 18F-FDG PET/CT Imaging
Authors: Tang Pan , Zhang Yifan , Tian Rong , Yang Guocai
Published: January 2022

We present a case of rib osteoblastoma in a patient with NK/T cell lymphoma. Osteoblastoma was incidentally found in a 63-year-old man in the axillary segment of the fifth rib and was misdiagnosed as lymphomatous involvement on staging 18F-FDG PET/CT. The radiological features in the CT component of PET/CT were atypical. After surgery, the diagnosis of osteoblastoma was confirmed by histopathologic findings.
Benign Parathyroid Hyperplasia With Incidental Pulmonary Seeding on 99mTc-MIBI Scintigraphy and FDG PET/CT
Authors: Tsai Yao-Kuang , Tsai Chi-Jung , Chiu Chuang-Hsin , Ko Kai-Hsiung , Li Yao-Feng
Published: January 2022

A 50-year-old woman with end-stage renal disease presented with recurrent hyperparathyroidism after parathyroidectomy. 99mTc-MIBI scintigraphy did not show MIBI-avid lesion in the neck or mediastinum but in bilateral lung fields instead. On suspicion of malignancy, 18F-FDG PET/CT was performed and depicted no significant FDG uptake throughout the whole body. After resection of the pulmonary nodules, the final histopathology revealed benign parathyroid hyperplasia with pulmonary seeding, which is exceptionally a rare entity.
An Unusual Presentation of Breast Implant Rupture
Authors: Hudson Anna , Brown Richard K. J. , Minoshima Satoshi , Dunn Dell
Published: January 2022

A 99mTc–methylene diphosphate (MDP) bone scintigraphy scan was performed to follow up metastatic breast cancer. A circular region of radiotracer uptake in the location of the patient's left breast implant was seen. Review of the same-day chest CT and the prior CT showed that the patient's breast implant had ruptured in the interim. The 99mTc-MDP uptake in the capsule of the breast implant was attributed to rupture, likely secondary to inflammation. This is an example of an unusual presentation of breast implant rupture discovered on a 99mTc-MDP bone scintigraphy scan.
Incidental Uptake of 68Ga-DOTATATE Gastrointestinal Stromal Tumor of Duodenum
Authors: Köroğlu Gizem , Görür Gözde Dağliöz , Doğan Sevtap , Bayrak Büşra Yaprak , Demir Hakan
Published: January 2022

A 56-year-old man underwent 68Ga-DOTATATE PET/CT with suspicion of a pancreatic neuroendocrine tumor. However, in this imaging, a mass with 68Ga-DOTATATE uptake was observed not in pancreas but in the duodenojejunal junction. Abdominal tomography confirmed that the heterogeneously enhanced mass was originated from duodenum. The patient was operated, and the histopathology result was evaluated as low-risk gastrointestinal stromal tumor. Although there was low or no specific binding to gastrointestinal stromal tumor cells for all 68Ga-labeled DOTA peptides, uptake of 68Ga-DOTATATE was observed incidentally in this case.
Alterations in 18F-FDG PET/MRI and 15O-Water PET Brain Findings in Patients With Neurological Symptoms After COVID-19 Vaccination
Authors: Siripongsatian Dheeratama , Kunawudhi Anchisa , Promteangtrong Chetsadaporn , Kiatkittikul Peerapon , Jantarato Attapon , Choolam Arthita , Ponglikitmongkol Krongkamol , Siripongboonsitti Taweegrit , Kaeowirun Tharathorn , Chotipanich Chanisa
Published: January 2022

Purpose

This study aimed to investigate functional abnormalities in the brain of patients with neurological adverse effects following COVID-19 (coronavirus disease 2019) vaccination using 18F-FDG PET/MRI and 15O-water PET.

Methods

Eight patients (1 man and 7 women, aged 26–47 years [median age, 36.5 years]) who experienced neurological symptoms after the first COVID-19 vaccination underwent CT, MRI, 18F-FDG PET/MRI, and 15O-water PET of the brain. After 7 days, each patient underwent a follow-up 18F-FDG PET/MRI and 15O-water PET of the brain. Imaging data were analyzed using visual and semiquantitative analyses, which included a cluster subtraction workflow (P = 0.05).

Results

There was no evidence of vascular abnormalities, acute infarction, or hemorrhage on the CT or MRI scans. On the 15O-water PET images, 1 patient had mildly significant decreases in perfusion in the bilateral thalamus and bilateral cerebellum, and another patient showed a diffuse increase in perfusion in the cerebral white matter. The visual and semiquantitative analyses showed hypometabolism in the bilateral parietal lobes in all 8 patients on both the first and follow-up 18F-FDG PET/MRI scans. Metabolic changes in the bilateral cuneus were also observed during the first visit; all patients exhibited neurological symptoms. Moreover, 6 patients showed hypometabolism, and 2 patients showed hypermetabolism.

Conclusion

All regions of metabolic abnormality were part of the fear network model that has been implicated in anxiety. Our study findings support the concepts of and provide evidence for the immunization stress-related response and the biopsychosocial model.
Effect of Cognitive Behavior Oriented Psychological Intervention on the Psychological Status of Depressed Facial Acne Scar Patients Undergoing Fractional Photothermolysis
Authors: Peng Yi , Bai Zhuanli , Guo Yuan , Hui Jie , Wang Juan , Ma Yanmei , Li Yang
Published: January 2022

Objective:

To explore the effect of cognitive behavior oriented psychological intervention on the psychological status of depressed facial acne scar patients receiving fractional photothermolysis.

Methods:

The study enrolled 48 depressed facial acne scar patients who received treatment at our hospital between May 2018 and May 2021. They were randomized to the control group and the fractional photothermolysis group with 24 patients in each group using the random number table method. They received nursing intervention and cognitive behavior-oriented psychological intervention, respectively.

Results:

The Hamilton Anxiety and Hamilton Depression scores were lower after intervention than before intervention in both groups,and the fractional photothermolysis group had lower Hamilton Anxiety and Hamilton Depression scores than the control group (P < 0.05). The interpersonal sensitivity had hostility and phobic anxiety scores were lower after 12 weeks of treatment than before intervention in both groups, and the fractional photothermolysis group had lower interpersonal sensitivity hostility and phobic anxiety scores than the control group (P < 0.05). The H, M, V, and P scores after 12 weeks of intervention were both lower in the 2 groups than those before intervention. The humanistic care quality of service nursing care and health education scores were lower after intervention before intervention in both groups and the fractional photothermolysis group had significantly lower humanistic care quality of service nursing care and health education scores than the control group (P< 0.05).

Conclusions:

Cognitive behavior-oriented psychological intervention can effectively improve the psychological status and psychological health of depressed facial acne scar patients receiving fractional photothermolysis.
Perceived Versus Verified Cancer History and Missed Opportunities for Donation in an Australian Cohort of Potential Deceased Solid Organ Donors
Authors: Hedley James A. , Kelly Patrick J. , Waller Karen M.J. , Thomson Imogen K. , De La Mata Nicole L. , Rosales Brenda M. , Wyburn Kate , Webster Angela C.
Published: January 2022

Background.

There is an imperative to maximize donation opportunities given ongoing organ shortages, but donor suitability assessments can be challenging.

Methods.

We analyzed an Australian cohort of potential deceased donors 2010 to 2013 to explore misclassification of cancer risk and potential strategies for improvement (decision support, real-time data linkage to existing data sets, and increasing risk tolerance). Cancer history perceived at referral was compared with verified cancer history in linked health records. Transmission risks were based on clinical guidelines. Potential donors declined due to cancer but verified low risk were missed opportunities; those accepted but verified high risk were excess-risk donors.

Results.

Among 472 potentially suitable donor referrals, 132 (28%) were declined because of perceived transmission risk and 340 (72%) donated. Assuming a low-risk threshold, there were 38/132 (29%) missed opportunities and 5/340 (1%) excess-risk donors. With decision support, there would have been 5 (13%) fewer missed opportunities and 2 (40%) more excess-risk donors; with real-time data linkage, 6 (16%) fewer missed opportunities and 2 (40%) fewer excess-risk donors; and with increased risk tolerance, 6 (16%) fewer missed opportunities and 11 (220%) more excess-risk donors.

Conclusions.

Potential donors’ cancer history is typically incomplete at referral. There are missed opportunities where decision support or more accurate cancer history could safely increase organ donors.
A Clinical Tool to Guide Selection and Utilization of Marginal Donor Livers With Graft Steatosis in Liver Transplantation
Authors: Steggerda Justin A. , Borja-Cacho Daniel , Brennan Todd V. , Todo Tsuyoshi , Nissen Nicholas N. , Bloom Matthew B. , Klein Andrew S. , Kim Irene K.
Published: January 2022

Background.

Donor liver biopsy (DLBx) in liver transplantation provides information on allograft quality; however, predicting outcomes from these allografts remains difficult.

Methods.

Between 2006 and 2015, 16 691 transplants with DLBx were identified from the Standard Transplant Analysis and Research database. Cox proportional hazard regression analyses identified donor and recipient characteristics associated with 30-d, 90-d, 1-y, and 3-y graft survival. A composite model, the Liver Transplant After Biopsy (LTAB) score, was created. The Mini-LTAB was then derived consisting of only donor age, macrosteatosis on DLBx, recipient model for end-stage liver disease score, and cold ischemic time. Risk groups were identified for each score and graft survival was evaluated. P values <0.05 were considered significant.

Results.

The LTAB model used 14 variables and 5 risk groups and identified low-, mild-, moderate-, high-, and severe-risk groups. Compared with moderate-risk recipients, severe-risk recipients had increased risk of graft loss at 30 d (hazard ratio, 3.270; 95% confidence interval, 2.568-4.120) and at 1 y (2.258; 1.928-2.544). The Mini-LTAB model identified low-, moderate-, and high-risk groups. Graft survival in Mini-LTAB high-risk transplants was significantly lower than moderate- or low-risk transplants at all time points.

Conclusions.

The LTAB and Mini-LTAB scores represent guiding principles and provide clinically useful tools for the successful selection and utilization of marginal allografts in liver transplantation.
Solid Organ Transplantation From SARS-CoV-2–infected Donors to Uninfected Recipients: A Single-center Experience
Authors: Jayasekera Channa R. , Vikram Holenarasipur R. , Rifat Zeeshan , Wagler Josiah , Okubo Keita , Braaksma Brandon R. , Harbell Jack W. , Jadlowiec Caroline C. , Katariya Nitin N. , Mathur Amit K. , Moss Adyr , Reddy K. Sudhakar , Singer Andrew , Orenstein Robert , Saling Christopher F. , Seville Maria T. , Mour Girish K. , Vargas Hugo E. , Byrne Thomas J. , Hewitt Winston R. , Aqel Bashar A.
Published: January 2022

Background.

The risk of donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in solid organ (heart, lung, liver, kidney, pancreas, and intestine) transplant recipients is poorly understood. Since hematogenous transmission of SARS-CoV-2 has not been documented to date, nonlung solid organs might be suitable for transplantation since they likely portend a low risk of viral transmission.

Methods.

Abdominal solid organs from SARS-CoV-2–infected donors were transplanted into uninfected recipients.

Results.

Between April 18, 2021, and October 30, 2021, we performed transplants of 2 livers, 1 simultaneous liver and kidney, 1 kidney, and 1 simultaneous kidney and pancreas from SARS-CoV-2–infected donors into 5 uninfected recipients. None of the recipients developed SARS-CoV-2 infection or coronavirus disease 2019, and when tested, allograft biopsies showed no evidence of SARS-CoV-2 RNA.

Conclusions.

Transplanting nonlung organs from SARS-CoV-2–infected donors into uninfected recipients demonstrated no evidence of virus transmission.
Evidence of early community transmission of Omicron (B1.1.529) in Delhi- A city with very high seropositivity and past-exposure!
Authors: Garg Rahul , Gautam Pramod , Suroliya Varun , Agarwal Reshu , Bhugra Arjun , Kaur Urvinder S. , Das Santanu , Bihari Chhagan , Agarwal Anil , Sarin S. K , Gupta Ekta
Published: January 2022

Background

Since identification, infections by new SARS-CoV-2 variant Omicron are rapidly increasing worldwide. There is huge gap of knowledge regarding virus behaviour in the population from low and middle income countries. Delhi being unique population with a high seropositivity and vaccination rate against COVID-19 infection. We aimed to study the epidemiological and clinical presentations of few early cases of community spread of Omicron infection in the state.

Methods

This is a prospective study where respiratory specimen from all RT-PCR confirmed positive cases between November 25th-December 23rd 2021 collected from five districts of Delhi were subjected to whole genome sequencing. Complete demographic and clinical details were recorded. We also analyzed the formation of local and familial clusters and eventual community transmission.

Findings

Out of the 264 cases included during study period, 68.9% (n=182)were identified as Delta and its sub-lineages while 31.06% (n=82) were Omicron with BA.1 as the predominant sub-lineage (73.1%). Most of the Omicron cases were asymptomatic (n=50,61%) and not requiring any hospitalizations. A total of 72 (87.8%) cases were fully vaccinated. 39.1% (n=32) had a history of travel and/or contacts while 60.9 (n=50) showed a community transmission. A steep increase in the daily progression of Omicron cases with its preponderance in the community was observed from 1.8% to 54%.

Interpretation

This study is among the first from India to provide the evidence of community transmission of Omicron with significantly increased breakthrough infections, decreased hospitalization rates, and lower rate of symptomatic infections among individuals with high seropositivity against SARS-CoV-2 infections.
Hebbian activity-dependent plasticity in white matter
Authors: Lazari Alberto , Salvan Piergiorgio , Cottaar Michiel , Papp Daniel , Rushworth Matthew , Johansen-Berg Heidi
Published: January 2022

Synaptic plasticity is required for learning and follows Hebb’s Rule, the com-putational principle underpinning associative learning. In recent years, a complementary type of brain plasticity has been identified in myelinated axons, which make up the majority of brain’s white matter. Like synaptic plasticity, myelin plasticity is required for learning, but it is unclear whether it is Hebbian or whether it follows different rules. Here, we provide evidence that white matter plasticity operates following Hebb’s Rule in humans. Across two experiments, we find that co-stimulating cortical areas to induce Hebbian plasticity leads to relative increases in cortical excitability and associated increases in a myelin marker within the stimulated fiber bundle. We conclude that Hebbian plasticity extends beyond synaptic changes, and can be observed in human white matter fibers.
Hippocampal Transplants of Fetal GABAergic Progenitors Regulate Adult Neurogenesis in Mice with Temporal Lobe Epilepsy
Authors: Arshad Muhammad N. , Oppenheimer Simon , Jeong Jaye , Buyukdemirtas Bilge , Naegele Janice R.
Published: January 2022

GABAergic interneurons within the dentate gyrus of the hippocampus regulate adult neurogenesis, including proliferation, migration, and maturation of new granule cells born in the subgranular zone (SGZ) of the dentate gyrus (DG). In temporal lobe epilepsy (TLE), some adult-born granule cells migrate ectopically into the hilus, and these cells contribute to increased hyperexcitability and seizures. Yet, transplanting embryonic day 13.5 fetal mouse medial ganglionic eminence (MGE) GABAergic progenitors into the hippocampus of mice with TLE ameliorates spontaneous seizures, due in part, to increased postsynaptic inhibition of adult-born granule cells. Here, we asked whether MGE progenitor transplantation affects earlier stages of adult neurogenesis, by comparing patterns of neurogenesis in naïve mice and epileptic (TLE) mice, with or without MGE transplants. In naïve and TLE mice, transplanted MGE cells showed comparable migration and process outgrowth. However, in TLE mice with MGE transplants, fewer adult-born Type 3 progenitors migrated ectopically. Furthermore, more Type 3 progenitors survived and migrated into the granule cell layer (GCL), as determined by immunostaining for doublecortin or the thymidine analogue, bromodeoxyuridine (BrdU). To determine whether MGE transplants affected earlier stages of adult neurogenesis, we compared proliferation in the SGZ two-hours after pulse labeling with BrdU in Naive vs. TLE mice and found no significant differences. Furthermore, MGE progenitor transplantation had no effect on cell proliferation in the SGZ. Moreover, when compared to naïve mice, TLE mice showed increases in inverted Type 1 progenitors and Type 2 progenitors, concomitant with a decrease in the normally oriented radial Type 1 progenitors. Strikingly, these alterations were abrogated by MGE transplantation. Thus, MGE transplants appear to reverse seizure-induced abnormalities in adult neurogenesis by increasing differentiation and radial migration of adult-born granule cell progenitors, outcomes that may ameliorate seizures.
PFTK1 kinase regulates axogenesis during development via RhoA activation
Authors: Rodríguez González Yasmilde , Kamkar Fatemeh , Jafar-nejad Paymaan , Wang Suzi , Qu Dianbo , Sanchez Alvarez Leticia , Hawari Dina , Sonnenfeld Margaret , Slack Ruth S. , Albert Paul , Park David S. , Joselin Alvin
Published: January 2022

PFTK1/Eip63E is a member of the Cyclin-dependent kinases (CDKs) family and plays an important role in normal cell cycle progression. Eip63E expresses primarily in postnatal and adult nervous system in Drosophila melanogaster but its role in CNS development remains unknown. We sought to understand the function of Eip63E in the CNS by studying the fly ventral nerve cord during development. Our results demonstrate that Eip63E regulates axogenesis in neurons and its deficiency leads to neuronal defects. Functional interaction studies performed using the same system identify an interaction between Eip63E and the small GTPase Rho1. Furthermore, deficiency of Eip63E homolog in mice, PFTK1, in a newly generated PFTK1 knockout mice results in increased axonal outgrowth confirming that the developmental defects observed in the fly model are due to defects in axogenesis. Importantly, RhoA phosphorylation and activity is affected by PFTK1 in primary neuronal cultures. We here report that GDP bound inactive RhoA is a substrate of PFTK1 and PFTK1 phosphorylation is required for RhoA activity. In conclusion, our work establishes an unreported neuronal role of PFTK1 in axon development mediated by phosphorylation and activation of GDP-bound RhoA. The results presented add to our understanding of the role of Cdks in the maintenance of RhoA mediated axon growth and its impact on CNS development and axonal regeneration.
Global monitoring of soil animal communities using a common methodology
Authors: Potapov Anton M. , Sun Xin , Briones Maria J. I. , Brown George G. , Cameron Erin K. , Cortet Jérôme , Eisenhauer Nico , Fujii Saori , Geisen Stefan , Gongalsky Konstantin B. , Guerra Carlos , Handa I.Tanya , Janion-Scheepers Charlene , Lindo Zoë , Mathieu Jérôme , Murvanidze Maka , Nielsen Uffe N , Scheu Stefan , Schmidt Olaf , Schneider Clement , Seeber Julia , Tuma Jiri , Tiunov Alexei V. , Zaitsev Andrey S. , Wall Diana H.
Published: January 2022

Here we introduce the Soil BON Foodweb Team, a cross-continental collaborative network that aims to monitor soil animal communities and food webs using consistent methodology at a global scale. Soil animals support vital soil processes via soil structure modification, direct consumption of dead organic matter, and interactions with microbial and plant communities. Soil animal effects on ecosystem functions have been demonstrated by correlative analyses as well as in laboratory and field experiments, but these studies typically focus on selected animal groups or species at one or few sites with limited variation in environmental conditions. The lack of comprehensive harmonised large-scale soil animal community data including microfauna, mesofauna, and macrofauna, in conjunction with related soil functions, limits our understanding of biological interactions in soil communities and how these interactions affect ecosystem functioning. To provide such data, the Soil BON Foodweb Team invites researchers worldwide to use a common methodology to address six long-term goals: (1) to collect globally representative harmonised data on soil micro-, meso-, and macrofauna communities; (2) to describe key environmental drivers of soil animal communities and food webs; (3) to assess the efficiency of conservation approaches for the protection of soil animal communities; (4) to describe soil food webs and their association with soil functioning globally; (5) to establish a global research network for soil biodiversity monitoring and collaborative projects in related topics; (6) to reinforce local collaboration networks and expertise and support capacity building for soil animal research around the world. In this paper, we describe the vision of the global research network and the common sampling protocol to assess soil animal communities and advocate for the use of standard methodologies across observational and experimental soil animal studies. We will use this protocol to conduct soil animal assessments and reconstruct soil food webs on the sites included in the global soil biodiversity monitoring network, Soil BON, allowing us to assess linkages among soil biodiversity, vegetation, soil physico-chemical properties, and ecosystem functions. In the present paper, we call for researchers especially from countries and ecoregions that remain underrepresented in the majority of soil biodiversity assessments to join us. Together we will be able to provide science-based evidence to support soil biodiversity conservation and functioning of terrestrial ecosystems.
Loss of plastid developmental genes coincides with a reversion to monoplastidy in hornworts
Authors: MacLeod Alexander I. , Raval Parth K. , Stockhorst Simon , Knopp Michael R. , Frangedakis Eftychios , Gould Sven B.
Published: January 2022

The first plastid evolved from an endosymbiotic cyanobacterium in the common ancestor of the Archaeplastida. The transformative steps from cyanobacterium to organelle included the transfer of control over developmental processes; a necessity for the host to orchestrate, for example, the fission of the organelle. The plastids of almost all embryophytes divide independent from nuclear division, leading to cells housing multiple plastids. Hornworts, however, are monoplastidic (or near-monoplastidic) and their photosynthetic organelles are a curious exception among embryophytes for reasons such as the occasional presence of pyrenoids. Here we screened genomic and transcriptomic data of eleven hornworts for components of plastid developmental pathways. We find intriguing differences among hornworts and specifically highlight that pathway components involved in regulating plastid development and biogenesis were differentially lost in this group of bryophytes. In combination with ancestral state reconstruction, our data suggest that hornworts have reverted back to a monoplastidic phenotype due to the combined loss of two plastid division-associated genes: ARC3 and FtsZ2.
Generation and characterisation of P. falciparum parasites with a G358S mutation in the PfATP4 Na+ pump and clinically relevant levels of resistance to some PfATP4 inhibitors
Authors: Qiu Deyun , Pei Jinxin V. , Rosling James E. O. , Li Dongdi , Xue Yi , Penington Jocelyn Sietsma , Kümpornsin Krittikorn , Vincent Aw Yi Tong , Han Aw Jessica Yi , Hasemer Heath , Dennis Adelaide S. M. , Ridgway Melanie C. , Papenfuss Anthony T. , Lee Marcus C. S. , van Dooren Giel G. , Kirk Kiaran , Lehane Adele M.
Published: January 2022

Small-molecule inhibitors of PfATP4, a Plasmodium falciparum protein that is believed to pump Na+ out of the parasite while importing H+, are on track to become much-needed new antimalarial drugs. The spiroindolone cipargamin is poised to become the first PfATP4 inhibitor to reach the field, having performed strongly in Phase 1 and 2 clinical trials. Previous attempts to generate cipargamin-resistant parasites in the laboratory have yielded parasites with reduced susceptibility to the drug; however, the highest 50% inhibitory concentration reported to date is 24 nM. Here, we show that P. falciparum parasites can acquire a clinically-significant level of resistance to cipargamin that enables them to withstand micromolar concentrations of the drug. Independent experiments to generate high-level cipargamin resistance using different protocols and strains led to the same change each time – a G358S mutation in PfATP4. Parasites with this mutation showed high-level resistance not only to cipargamin, but also to the dihydroisoquinolone (+)-SJ733. However, for certain other (less clinically advanced) PfATP4-associated compounds the G358S mutation in PfATP4 conferred only moderate resistance or no resistance. The G358S mutation in PfATP4 did not affect parasite susceptibility to antimalarials that do not target PfATP4. The G358S mutation in PfATP4, and the equivalent mutation in the Toxoplasma gondii ATP4 homologue (G419S), decreased the sensitivity of the Na+-ATPase activity of ATP4 to inhibition by cipargamin and (+)-SJ733, and decreased the sensitivity of parasites expressing these ATP4 mutations to disruption of parasite Na+ regulation by cipargamin- and (+)-SJ733. The G358S mutation in PfATP4 reduced the affinity of the protein for Na+ and was associated with an increase in the parasite’s resting cytosolic Na+ concentration; however, no significant defect in parasite growth rate was observed. Our findings suggest that codon 358 in pfatp4 should be monitored closely in the field as a molecular marker for cipargamin resistance, and that PfATP4 inhibitors in clinical development should be tested for their activity against PfATP4G358S parasites.
Optimal control methods for nonlinear parameter estimation in biophysical neuron models
Authors: Kadakia Nirag
Published: January 2022

Functional forms of biophysically-realistic neuron models are constrained by neurobiological and anatomical considerations, such as cell morphologies and the presence of known ion channels. Despite these constraints, neurons models still contain unknown static parameters which must be inferred from experiment. This inference task is most readily cast into the framework of state-space models, which systematically takes into account partial observability and measurement noise. Inferring only dynamical state variables such as membrane voltages is a well-studied problem, and has been approached with a wide range of techniques beginning with the well-known Kalman filter. Inferring both states and fixed parameters, on the other hand, is less straightforward. Here, we develop a method for joint parameter and state inference that combines traditional state space modeling with chaotic synchronization and optimal control. Our methods are tailored particularly to situations with considerable measurement noise, sparse observability, very nonlinear or chaotic dynamics, and highly uninformed priors. We illustrate our approach both in a canonical chaotic model and in a phenomenological neuron model, showing that many unknown parameters can be uncovered reliably and accurately from short and noisy observed time traces. Our method holds promise for estimation in larger-scale systems, given ongoing improvements in calcium reporters and genetically-encoded voltage indicators.
Horizontal Transfers Lead to the Birth of Momilactone Biosynthetic Gene Clusters in Grass
Authors: Wu Dongya , Hu Yiyu , Akashi Shota , Nojiri Hideaki , Ye Chu-Yu , Zhu Qian-Hao , Okada Kazunori , Fan Longjiang
Published: January 2022

Momilactone A, an important plant labdane-related diterpenoid, functions as a phytoalexin against pathogens and an allelochemical against neighboring plants. The genes involved in biosynthesis of momilactone A are found in clusters, i.e., MABGCs (Momilactone A biosynthetic gene clusters), in the rice and barnyardgrass genomes. How MABGCs originate and evolve is still not clear. Here, we integrated results from comprehensive phylogeny and comparative genomic analyses of the core genes of MABGC-like clusters and MABGCs in 40 monocot plant genomes, providing convincing evidence for the birth and evolution of MABGCs in grass species. The MABGCs found in the PACMAD clade of the core grass lineage (including Panicoideae and Chloridoideae) originated from a MABGC-like cluster in Triticeae (BOP clade) via horizontal gene transfer (HGT) and followed by recruitment of MAS and CYP76L1 genes. The MABGCs in Oryzoideae originated from PACMAD through another HGT event and lost CYP76L1 afterwards. The Oryza MABGC and another Oryza diterpenoid cluster c2BGC are two distinct clusters, with the latter being originated from gene duplication and relocation within Oryzoideae. Further comparison of the expression patterns of the MABGC genes between rice and barnyardgrass in response to pathogen infection and allelopathy provides novel insights into the functional innovation of MABGCs in plants. Our results demonstrate HGT-mediated origination of MABGCs in grass and shed lights into the evolutionary innovation and optimization of plant biosynthetic pathways.
A unique dexamethasone-dependent gene expression profile in the lungs of COVID-19 patients
Authors: Fahnøe Ulrik , Ronit Andreas , Berg Ronan M. G. , Jørgensen Sofie E. , Mogensen Trine H. , Underwood Alexander P. , Scheel Troels K. H. , Bukh Jens , Plovsing Ronni R.
Published: January 2022

Local immunopathogenesis of COVID-19 acute respiratory distress syndrome (CARDS) and the effects of systemic dexamethasone (DXM) treatment on pulmonary immunity in COVID-19 remain insufficiently understood. To provide further insight into insight into immune regulatory mechanisms in the lungs of CARDS (with and without DXM treatment) and critically ill non-COVID-19 patients (without DXM treatment), transcriptomic RNA-seq analysis of bronchoalveolar lavage fluid (BALF) was performed in these patients. Functional analysis was performed using gene ontology and a blood transcription module, and gene expression of select pro-inflammatory cytokines, interferon-stimulated genes (ISGs) and auto-IFN antibodies were assessed. We found 550 and 2173 differentially expressed genes in patients with non-DXM-CARDS and DXM-CARDS, respectively. DXM-CARDS was characterized by upregulation of genes related to pulmonary innate and adaptive immunity, notably B-cell and complement pathway activation, antigen presentation, phagocytosis and FC-gamma receptor signalling. Pro-inflammatory genes were not differentially expressed in CARDS vs. non-COVID-19, nor did they differ according to DXM. Most ISGs were specifically upregulated in CARDS, particularly in non-DXM-CARDS. Auto-IFN autoantibodies were detectable in BALF of some CARDS patients. In conclusion, DXM treatment was not associated with regulation of pro-inflammatory pathways in CARDS but with regulation of other specific local innate and adaptive immune responses.

summary

This study identifies differentially expressed genes in bronchoalveolar fluid of COVID-19 acute respiratory distress patients with a distinct RNA expression profile of those treated with dexamethasone. These results challenge the concept of a COVID-19 specific cytokine storm.
Incidence and Risk Factors of Immediate Hypersensitivity Reactions and Immunisation Stress-related Responses with COVID-19 mRNA Vaccine
Authors: Imai Kazuo , Tanaka Fumika , Kawano Shuichi , Esaki Kotoba , Arakawa Junko , Nishiyama Takashi , Seno Soichiro , Hatanaka Kosuke , Sugiura Takao , Kodama Yu , Yamada Seigo , Iwamoto Shinichiro , Takesima Shigeto , Abe Nobujiro , Kamae Chikako , Aono Shigeaki , Ito Toshimitsu , Yamamoto Tetsuo , Mizuguchi Yasunori
Published: January 2022

Background

With the implementation of mass vaccination campaigns against COVID-19, the safety of vaccine needs to be evaluated.

Objective

We aimed to assess the incidence and risk factors for immediate hypersensitivity reactions (IHSR) and immunisation stress-related responses (ISRR) with the Moderna COVID-19 vaccine.

Methods

This nested case-control study included recipients who received the Moderna vaccine at a mass vaccination centre, Japan. Recipients with IHSR and ISRR were designated as cases 1 and 2, respectively. Controls 1 and 2 were selected from recipients without IHSR or ISRR and matched (1:4) with cases 1 and cases 2, respectively. Conditional logistic regression analysis was used to identify risk factors associated with IHSR and ISRR.

Results

Of the 614,151 vaccine recipients who received 1,201,688 vaccine doses, 306 recipients (cases 1) and 2,478 recipients (cases 2) showed 318 events of IHSR and 2,558 events of ISRR, respectively. The incidence rates per million doses were estimated as – IHSR: 266 cases, ISRR: 2,129 cases, anaphylaxis: 2 cases, and vasovagal syncope: 72 cases. Risk factors associated with IHSR included female, asthma, atopic dermatitis, thyroid diseases, and history of allergy; for ISRR, they were younger age, female, asthma, thyroid diseases, mental disorders, and a history of allergy and vasovagal reflex.

Conclusion

In the mass vaccination settings, the Moderna vaccine can be used safely owing to the low incidence rates of IHSR and anaphylaxis. However, providers should beware of the occurrence of ISRR. Risk factor identification may contribute to the stratification of high-risk recipients for IHSR and ISRR.
Evidence from human placenta, ER-stressed trophoblasts and transgenic mice links transthyretin proteinopathy to preeclampsia
Authors: Cheng Shibin , Huang Zheping , Banerjee Sayani , Buxbaum Joel N. , Sharma Surendra
Published: January 2022

We have demonstrated that protein aggregation plays a pivotal role in the pathophysiology of preeclampsia (PE) and identified several aggregated proteins in the circulation of PE patients, most significantly the serum protein transthyretin (TTR). Here we show robust accumulation of TTR aggregates in the placentas of women with early-onset PE (e-PE). TTR aggregation was inducible in primary human trophoblasts (PHTs) and the TCL-1 trophoblast cell line by ER stress inducers or autophagy-lysosomal disruptors. Hypoxia/reoxygenation (H/R) of cultured PHTs increased intracellular BiP, phosphorylated IRE1α, PDI and Ero-1, all markers of the UPR, and the apoptosis mediator caspase-3. Blockade of IRE1α inhibited H/R-induced upregulation of Ero-1 in PHTs. Excessive UPR was observed in the PE placenta. Further, pregnant mice, overexpressing transgene encoded wild type human TTR, displayed aggregated TTR in the junctional zone of the placenta and PE-like features including hypertension, proteinuria, intrauterine growth restriction, kidney injury, and elevated levels of the PE biomarkers serum sFlt-1 and endoglin. High Resolution Ultrasound analysis revealed low blood flow in uterine and umbilical arteries compared to that found in wild type pregnant mice. On the other hand, loss of mouse TTR function did not cause any pregnancy abnormalities in Ttr-/- mice. These observations in the PE placenta, cultured trophoblast cells and TTR transgenic mice indicate that TTR aggregation is an important causal contributor to PE pathophysiology.