bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral Polio Vaccine to Mitigate the Risk of Illness and Mortality During the Coronavirus Disease 2019 Pandemic: A Cluster-Randomized Trial in Guinea-Bissau
Authors: Fisker Ane B , Martins Justiniano S D , Nanque Line M , Jensen Andreas M , Ca Elsi J C , Nielsen Sebastian , Martins Cesario L , Rodrigues Amabelia
Published: September 2022

Background

Oral polio vaccine (OPV) may improve resistance to non-polio-infections. We tested whether OPV reduced the risk of illness and mortality before coronavirus disease 2019 (COVID-19) vaccines were available.

Methods

During the early COVID-19 pandemic, houses in urban Guinea-Bissau were randomized 1:1 to intervention or control. Residents aged 50+ years were invited to participate. Participants received bivalent OPV (single dose) or nothing. Rates of mortality, admissions, and consultation for infections (primary composite outcome) during 6 months of follow-up were compared in Cox proportional hazards models adjusted for age and residential area. Secondary outcomes included mortality, admissions, consultations, and symptoms of infection.

Results

We followed 3726 participants (OPV, 1580; control, 2146) and registered 66 deaths, 97 admissions, and 298 consultations for infections. OPV did not reduce the risk of the composite outcome overall (hazard ratio [HR] = 0.97; 95% confidence interval [CI], .79–1.18). OPV reduced the risk in males (HR = 0.71; 95% CI, .51–.98) but not in females (HR = 1.18; 95% CI, .91–1.52) (P for same effect = .02). OPV also reduced the risk in Bacillus Calmette-Guérin scar-positive (HR = 0.70; 95% CI, .49–.99) but not in scar-negative participants (HR = 1.13; 95% CI, .89–1.45) (P = .03). OPV had no overall significant effect on mortality (HR = 0.96; 95% CI, .59–1.55), admissions (HR = 0.76; 95% CI, .49–1.17) or recorded consultations (HR = 0.99; 95% CI, .79–1.25), but the OPV group reported more episodes with symptoms of infection (6050 episodes; HR = 1.10 [95% CI, 1.03–1.17]).

Conclusions

In line with previous studies, OPV had beneficial nonspecific effects in males.
Natural Language Processing and Machine Learning to Identify People Who Inject Drugs in Electronic Health Records
Authors: Goodman-Meza David , Tang Amber , Aryanfar Babak , Vazquez Sergio , Gordon Adam J , Goto Michihiko , Goetz Matthew Bidwell , Shoptaw Steven , Bui Alex A T
Published: September 2022

Background

Improving the identification of people who inject drugs (PWID) in electronic medical records can improve clinical decision making, risk assessment and mitigation, and health service research. Identification of PWID currently consists of heterogeneous, nonspecific International Classification of Diseases (ICD) codes as proxies. Natural language processing (NLP) and machine learning (ML) methods may have better diagnostic metrics than nonspecific ICD codes for identifying PWID.

Methods

We manually reviewed 1000 records of patients diagnosed with Staphylococcus aureus bacteremia admitted to Veterans Health Administration hospitals from 2003 through 2014. The manual review was the reference standard. We developed and trained NLP/ML algorithms with and without regular expression filters for negation (NegEx) and compared these with 11 proxy combinations of ICD codes to identify PWID. Data were split 70% for training and 30% for testing. We calculated diagnostic metrics and estimated 95% confidence intervals (CIs) by bootstrapping the hold-out test set. Best models were determined by best F-score, a summary of sensitivity and positive predictive value.

Results

Random forest with and without NegEx were the best-performing NLP/ML algorithms in the training set. Random forest with NegEx outperformed all ICD-based algorithms. F-score for the best NLP/ML algorithm was 0.905 (95% CI, .786–.967) and 0.592 (95% CI, .550–.632) for the best ICD-based algorithm. The NLP/ML algorithm had a sensitivity of 92.6% and specificity of 95.4%.

Conclusions

NLP/ML outperformed ICD-based coding algorithms at identifying PWID in electronic health records. NLP/ML models should be considered in identifying cohorts of PWID to improve clinical decision making, health services research, and administrative surveillance.
Contribution of zooplankton nutrient recycling and effects on phytoplankton size structure in a hypereutrophic reservoir
Authors: Butts Tyler J , Moody Eric K , Wilkinson Grace M
Published: September 2022

Consumer nutrient recycling influences aquatic ecosystem functioning by altering the movement and transformation of nutrients. In hypereutrophic reservoirs, zooplankton nutrient recycling has been considered negligible due to high concentrations of available nutrients. A comparative analysis ( Moody and Wilkinson, 2019) found that zooplankton communities in hypereutrophic lakes are dominated by nitrogen (N)-rich species, which the authors hypothesized would increase phosphorus (P) availability through excretion. However, zooplankton nutrient recycling likely varies over the course of a growing season due to changes in biomass, community composition and grazing pressure on phytoplankton. We quantified zooplankton, phytoplankton and nutrient concentration dynamics during the summer of 2019 in a temperate, hypereutrophic reservoir. We found that the estimated contribution of zooplankton excretion to the dissolved nutrient pool on a given day was equivalent to a substantial proportion (21–39%) of the dissolved inorganic P standing stock in early summer when P concentrations were low and limiting phytoplankton growth. Further, we found evidence that zooplankton affected phytoplankton size distributions through selective grazing of smaller phytoplankton cells likely affecting nutrient uptake and storage by phytoplankton. Overall, our results demonstrate zooplankton excretion in hypereutrophic reservoirs likely helped drive springtime phytoplankton dynamics through nutrient recycling while grazing influenced phytoplankton size distributions.
The Risk of Implicit Guarantees: Evidence from Shadow Banks in China
Authors: Huang Ji , Huang Zongbo , Shao Xiang
Published: September 2022

We study how risks spill over from shadow banking activities to traditional banks through implicit guarantees. Using data on wealth management products (WMPs), China’s largest shadow banking component, we find that banks with higher interbank borrowing rates strategically provide stronger implicit guarantees to their issued WMPs. Extending implicit guarantees builds bank reputations and reduces rollover costs while exposing banks to losses from shadow banking activities. Our findings thus suggest a bank-specific approach to assessing the risk of implicit guarantees based on transparent and real-time interbank rates.
Diagnostic Reference Levels for Common CT Examinations: Results from a Statewide dose Survey
Authors: Jusoh Irwan Iskandar , Abdullah Kamarul Amin , Ali Mohd Hanafi
Published: September 2022

The aim of this study was to investigate the current radiation doses for CT examinations throughout a state in Malaysia and, based on this data, to propose local diagnostic reference levels (DRLs) for the most common CT examinations. A study was conducted in three of the four hospitals that have provided CT services throughout the state. A survey booklet was designed to facilitate collection of pertinent CT scan data. The following information were extracted and recorded for each study: tube voltage, tube current, number of scans phases, CT dose index volume (CTDIvol) and dose length product (DLP). Proposed local DRLs of CT brain and thorax were up to 12% lower than the current national DRLs. However, an increase of DLP (median value) for CT abdomen was also found as compared to the 75th percentile of national DRLs. Therefore, considerable optimisation should be made to achieve a better dose reduction.
Endophytic Bacterium Lysobacter firmicutimachus Strain 5-7 Is a Promising Biocontrol Agent Against Rice Seedling Disease Caused by Pythium arrhenomanes in Nursery Trays
Authors: Tu Chi-Kuan , Wang Pei-Han , Lee Miin-Huey
Published: September 2022

Rice root rot disease caused by Pythium spp. is a highly destructive disease in rice nurseries. Biocontrol with endophytic bacteria was developed in this study to control rice seedling diseases. An in planta screening assay revealed that two bacterial endophytes, strains 5-7 and 6-4, displayed strong protection of rice seedlings from attack by Pythium arrhenomanes. Phylogenetic analysis indicated that strain 5-7 is Lysobacter firmicutimachus, while strain 6-4 belongs to the Kitasatospora genus. To quickly evaluate the disease severity of the root system damaged by Pythium spp. in nursery trays, a root surface area measurement assay was developed. By using this measurement, the control efficacy in nursery trays was evaluated, and L. firmicutimachus 5-7 showed promising biocontrol activity against Pythium disease. In a field trial, the two endophytes exhibited significant disease control efficacy on rice brown spot disease caused by Bipolaris oryzae naturally occurring in a commercial nursery field. The two endophytes exhibited multiple enzymatic activities and broad-spectrum antagonistic activities against multiple rice pathogens. The two endophytes colonized the root surface and inside of the root. L. firmicutimachus 5-7 primarily colonized the intercellular space and aerenchyma. Antibiosis is the major mechanism used by strain 5-7 to cause Bipolaris hyphal swelling and inhibit Pythium zoospore germination and sporangium formation, while a hyperparasitism-like phenomenon was found in the interaction of strain 6-4 with Pythium and Bipolaris hyphae. In conclusion, we report the promising biocontrol agent L. firmicutimachus 5-7 and the potential biocontrol agent Kitasatospora sp. 6-4 for disease control of rice seedlings in commercial nursery trays and their possible mechanisms of action.
Plant Viruses of Agricultural Importance: Current and Future Perspectives of Virus Disease Management Strategies
Authors: Tatineni Satyanarayana , Hein Gary L.
Published: September 2022

Plant viruses cause significant losses in agricultural crops worldwide, affecting the yield and quality of agricultural products. The emergence of novel viruses or variants through genetic evolution and spillover from reservoir host species, changes in agricultural practices, mixed infections with disease synergism, and impacts from global warming pose continuous challenges for the management of epidemics resulting from emerging plant virus diseases. This review describes some of the most devastating virus diseases plus select virus diseases with regional importance in agriculturally important crops that have caused significant yield losses. The lack of curative measures for plant virus infections prompts the use of risk-reducing measures for managing plant virus diseases. These measures include exclusion, avoidance, and eradication techniques, along with vector management practices. The use of sensitive, high throughput, and user-friendly diagnostic methods is crucial for defining preventive and management strategies against plant viruses. The advent of next-generation sequencing technologies has great potential for detecting unknown viruses in quarantine samples. The deployment of genetic resistance in crop plants is an effective and desirable method of managing virus diseases. Several dominant and recessive resistance genes have been used to manage virus diseases in crops. Recently, RNA-based technologies such as dsRNA- and siRNA-based RNA interference, microRNA, and CRISPR/Cas9 provide transgenic and nontransgenic approaches for developing virus-resistant crop plants. Importantly, the topical application of dsRNA, hairpin RNA, and artificial microRNA and trans-active siRNA molecules on plants has the potential to develop GMO-free virus disease management methods. However, the long-term efficacy and acceptance of these new technologies, especially transgenic methods, remain to be established.
MRI of Cerebrovascular Injury Associated With COVID-19 and Non-COVID-19 Acute Respiratory Distress Syndrome: A Matched Case-Control Study
Authors: Shoskes Aaron , Huang Merry , Gedansky Aron , Hassett Catherine , Buletko A. Blake , Duggal Abhijit , Uchino Ken , Cho Sung-Min
Published: September 2022

OBJECTIVES:

Cerebrovascular injury associated with COVID-19 has been recognized, but the mechanisms remain uncertain. Acute respiratory distress syndrome (ARDS) is a severe pulmonary injury, which is associated with both ischemic and hemorrhagic stroke. It remains unclear if cerebrovascular injuries associated with severe COVID-19 are unique to COVID-19 or a consequence of severe respiratory disease or its treatment. The frequency and patterns of cerebrovascular injury on brain MRI were compared among patients with COVID-19 ARDS and non-COVID-19 ARDS.

DESIGN:

A case-control study.

SETTING:

A tertiary academic hospital system

PATIENTS:

Adult patients (>18 yr) with COVID-19 ARDS (March 2020 to July 2021) and non-COVID-19 ARDS (January 2010-October 2018) who underwent brain MRI during their index hospitalization.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Cerebrovascular injury on MRI included cerebral ischemia (ischemic infarct or hypoxic ischemic brain injury) and intracranial hemorrhage (intraparenchymal, subarachnoid, or subdural, and cerebral microbleed [CMB]).

Twenty-six patients with COVID-19 ARDS and sixty-six patients with non-COVID ARDS underwent brain MRI during the index hospitalization, resulting in 23 age- and sex-matched pairs. The frequency of overall cerebrovascular injury (57% vs 61%), cerebral ischemia (35% vs 43%), intracranial hemorrhage (43% vs 48%), and CMB (52% vs 41%) between COVID-19 ARDS and non-COVID-19 ARDS patients was similar (all p values >0.05). However, four of 26 patients (15%) with COVID-19 and no patients with non-COVID-19 ARDS had disseminated leukoencephalopathy with underlying CMBs, an imaging pattern that has previously been reported in patients with COVID-19.

CONCLUSIONS:

In a case-control study of selected ARDS patients with brain MRI, the frequencies of ischemic and hemorrhagic cerebrovascular injuries were similar between COVID-19 versus non-COVID-19 ARDS patients. However, the MRI pattern of disseminated hemorrhagic leukoencephalopathy was unique to the COVID-19 ARDS patients in this cohort.
Prognostic factors in primary central nervous system lymphoma
Authors: Morales-Martinez Andrea , Nichelli Lucia , Hernandez-Verdin Isaias , Houillier Caroline , Alentorn Agustí , Hoang-Xuan Khê
Published: September 2022

Purpose of review

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal diffuse large B cell lymphoma. Despite its apparent immunopathological homogeneity, PCNSL displays a wide variability in outcome. Identifying prognostic factors is of importance for patient stratification and clinical decision-making. The purpose of this review is to focus on the clinical, neuroradiological and biological variables correlated with the prognosis at the time of diagnosis in immunocompetent patients.

Recent findings

Age and performance status remain the most consistent clinical prognostic factors. The current literature suggests that neurocognitive dysfunction is an independent predictor of poor outcome. Cumulating data support the prognostic value of increased interleukin-10 level in the cerebrospinal fluid (CSF), in addition to its interest as a diagnostic biomarker. Advances in neuroimaging and in omics have identified several semi-quantitative radiological features (apparent diffusion restriction measures, dynamic contrast-enhanced perfusion MRI (pMRI) pattern and 18F-fluorodeoxyglucose metabolism) and molecular genetic alterations with prognostic impact in PCNSL.

Validation of new biologic and neuroimaging markers in prospective studies is required before integrating future prognostic scoring systems. In the era of radiomic, large clinicoradiological and molecular databases are needed to develop multimodal artificial intelligence algorithms for the prediction of accurate outcome.
Is the world ready for the STICH 3.0 trial?
Authors: Vervoort Dominique , Jolicoeur Marc E. , Marquis-Gravel Guillaume , Fremes Stephen E.
Published: September 2022

Purpose of review

Coronary artery disease (CAD) is responsible for >50% of heart failures cases. Patients with ischemic left ventricular systolic dysfunction (iLVSD) are known to have poorer outcomes after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) compared to patients with a normal ejection fraction. Nevertheless, <1% of patients in coronary revascularization trials to date had iLVSD. The purpose of this review is to describe coronary revascularization modalities in patients with iLVSD and highlight the need for randomized controlled trial evidence comparing these treatments in this patient population.

Recent findings

Network meta-analytic findings of observational studies suggest that PCI is associated with higher rates of mortality, cardiac death, myocardial infarction, and repeat revascularization but not stroke compared to CABG in iLVSD. In recent years, outcomes for patients undergoing PCI have improved as a result of advances in technologies and techniques.

The optimal coronary revascularization modality in patients with iLVSD remains unknown. In observational studies, CABG appears superior to PCI; however, direct randomized evidence is absent and developments in PCI techniques have improved post-PCI outcomes in recent years. The Surgical Treatment for Ischemic Heart Failure 3.0 consortium of trials will seek to address the clinical equipoise in coronary revascularization in patients with iLVSD.
Sex differences in pressure and flow waveform physiology across the life course
Authors: Picone Dean S. , Kodithuwakku Vimarsha , Mayer Christopher C. , Chapman Niamh , Rehman Sabah , Climie Rachel E.
Published: September 2022

Cardiovascular disease (CVD) has long been deemed a disease of old men. However, in 2019 CVD accounted for 35% of all deaths in women and, therefore, remains the leading cause of death in both men and women. There is increasing evidence to show that risk factors, pathophysiology and health outcomes related to CVD differ in women compared with men, yet CVD in women remains understudied, underdiagnosed and undertreated. Differences exist between the sexes in relation to the structure of the heart and vasculature, which translate into differences in blood pressure and flow waveform physiology. These physiological differences between women and men may represent an important explanatory factor contributing to the sex disparity in CVD presentation and outcomes but remain understudied. In this review we aim to describe sex differences in arterial pressure and flow waveform physiology and explore how they may contribute to differences in CVD in women compared to men. Given that unfavourable alterations in the cardiovascular structure and function can start as early as in utero, we report sex differences in waveform physiology across the entire life course.
Metaplasticity: a key to visual recovery from amblyopia in adulthood?
Authors: Leet Madison P. , Bear Mark F. , Gaier Eric D.
Published: September 2022

Purpose of review

We examine the development of amblyopia and the effectiveness of conventional and emerging therapies through the lens of the Bienenstock, Cooper, and Munro (BCM) theory of synaptic modification.

Recent findings

The BCM theory posits metaplastic adjustment in the threshold for synaptic potentiation, governed by prior neuronal activity. Viewing established clinical principles of amblyopia treatment from the perspective of the BCM theory, occlusion, blur, or release of interocular suppression reduce visual cortical activity in the amblyopic state to lower the modification threshold and enable amblyopic eye strengthening. Although efficacy of these treatment approaches declines with age, significant loss of vision in the fellow eye by damage or disease can trigger visual acuity improvements in the amblyopic eye of adults. Likewise, reversible retinal inactivation stimulates recovery of amblyopic eye visual function in adult mice and cats.

Conventional and emerging amblyopia treatment responses abide by the framework of BCM theory. Preclinical studies support that the dramatic reduction in cortical activity accompanying temporary retinal silencing can promote recovery from amblyopia even in adulthood, highlighting a promising therapeutic avenue.
Treatment of metastatic uveal melanoma in 2022: improved treatment regimens and improved prognosis
Authors: Reichstein David , Brock Anderson , Lietman Caressa , McKean Meredith
Published: September 2022

Purpose of review

Until recently, metastatic uveal melanoma was associated with essentially uniform fatality within months. However, recent developments in screening, improved understanding of the genetic underpinnings of metastatic disease, and pivotal medication approvals have improved the disease's rate of fatality.

Recent findings

Routine implementation of genetic testing at the time of primary tumor treatment via gene expression profiling or chromosomal analysis has identified patients who are at high risk for metastatic disease. Enhanced screening with imaging directed at the liver and lungs has allowed for identification of early disease and lower tumor burden. Significant work on improved liver directed therapy along with systemic chemotherapy and immunotherapy has improved life expectancy. The first systemic immunotherapy specifically for metastatic uveal melanoma was approved this year. This medication, tebentafusp, is likely to improve life expectancy for all patients with metastatic melanoma assuming they have appropriate human leukocyte antigen (HLA) markers. Multiple clinical trials with novel immunotherapeutic agents are promising as well.

The prognosis for patients with uveal melanoma is far better than ever before because of recent developments in the understanding and treatment of metastatic disease.
Optimizing Management of Asymmetric Ptosis: A Comparison of Three Posterior Approach Resection Algorithms
Authors: Roelofs Kelsey A. , Margines Jack B. , Chen Teresa , Goodyear Kendall , Goldberg Robert A. , Rootman Daniel B.
Published: September 2022

Purpose:

The purpose of this study was to compare the efficacy of 3 resection algorithms in the management of patients with asymmetric ptosis.

Methods:

Patients undergoing bilateral Muller’s muscle-conjunctival resection (MMCR) were identified. Standardized preoperative clinical photographs were examined and margin reflex distance 1 (MRD1) was measured using ImageJ. Patients presenting with ≥1 mm of asymmetry in MRD1 were included. Three groups were identified: variable (4:1 ratio, with the lower side receiving a greater resection), fixed (7 mm resection bilaterally), and tarsectomy (7 mm bilaterally + 1 mm of tarsus resected on the lower preoperative side). Postoperative MRD1 was measured from photographs obtained 3 months after surgery. The primary outcome was postoperative asymmetry.

Results:

A total of 95 patients with a mean age of 71.0 ± 11.0 years were included. There was no significant difference in age (p = 0.277) or length of follow-up (p = 0.782) between the groups. Although the fixed tarsectomy group had significantly greater preoperative asymmetry (p = 0.001), there was no significant difference in postoperative asymmetry (p = 0.166). On multivariate analysis, preoperative asymmetry was the only significant predictor of postoperative asymmetry (p < 0.001). Specifically, the surgical group was not a predictor of the primary outcome (p = 0.723).

Conclusions:

Resection amount and technique did not predict postoperative outcomes in cases of asymmetric ptosis. This may support the hypothesis that changes in eyelid position and symmetry following MMCR is due to a dynamic system, rather than as a result of purely mechanical forces.
Severe Orbital Congestion After a Brow Lift Due to an Osteodural Arteriovenous Fistula
Authors: Brossard-Barbosa Natalie , Krings Timo , Margolin Edward
Published: September 2022

The authors describe a 73-year-old woman who developed worsening proptosis, binocular diplopia, and periorbital pain shortly after undergoing an open subperiosteal brow lift procedure. She was found to have a pre-existing osteodural fistula (ODF) within left frontal bone, which was draining through supraorbital vein (SOV) in cavernous sinus. When SOV was inadvertently severed during a brow lift, blood from the fistula was now redirected in the orbit. This is the first report of a decompensated ODF after a brow lift procedure. It underscores the complexity of orbital venous drainage and the importance in preserving the supraorbital and supratrochlear veins during brow lift.
SARS-CoV-2 Seroprevalence in Employees of Four Essential Non–Health Care Sectors at Moderate/High Risk of Exposure to Coronavirus Infection
Authors: Belloni Giulia , Dupraz Julien , Butty Audrey , Pasquier Jérôme , Estoppey Sandrine , Bochud Murielle , Gonseth-Nussle Semira , D'Acremont Valérie
Published: September 2022

Objective

The aim of this study was to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in Swiss non–health care employees at a moderate to high risk of exposure: bus drivers and supermarket, laundry service, and mail-sorting center employees.

Methods

Data on 455 essential workers included demographics, SARS-CoV-2 exposure and use of protective measures. Anti–SARS-CoV-2 immunoglobulins G and A targeting the spike protein were measured between May and July 2020.

Results

The overall crude seroprevalence estimate (15.9%; 95% confidence interval [CI], 12.6% to 19.7%) among essential workers was not significantly higher than that of the general working-age population (11.2%; 95% CI, 7.1% to 15.2%). Seroprevalence ranged from 11.9% (95% CI, 6.3% to 19.8%) among bus drivers to 22.0% (95% CI, 12.6% to 19.7%) among food supermarket employees.

Conclusions

We found no significant difference in seroprevalence between our sample of essential workers and local working-age population during the first lockdown phase of the COVID-19 pandemic. Having a seropositive housemate was the strongest predictor of SARS-CoV-2 seropositivity.
Which patients with CKD will benefit from genomic sequencing? Synthesizing progress to illuminate the future
Authors: Mallett Andrew J.
Published: September 2022

Purpose of review

This review will summarize and synthesize recent findings in regard to monogenic kidney disorders, including how that evidence is being translated into practice. It will add to existing key knowledge to provide context for clinicians in consolidating existing practice and approaches.

Recent findings

Whilst there are long established factors, which indicate increased likelihood of identifying a monogenic cause for kidney disease, these can now be framed in terms of the identification of new genes, new indications for genomic testing and new evidence for clinical utility of genomic testing in nephrology. Further, inherent in the use of genomics in nephrology are key concepts including robust informed consent, variant interpretation and return of results. Recent findings of variants in genes related to complex or broader kidney phenotypes are emerging in addition to understanding of de novo variants. Phenocopy phenomena are indicating a more pragmatic use of broader gene panels whilst evidence is emerging of a role in unexplained kidney disease. Clinical utility is evolving but is being successfully demonstrated across multiple domains of outcome and practice.

We provide an updated framework of evidence to guide application of genomic testing in chronic kidney disease (CKD), building upon existing principles and knowledge to indicate how the practice and implementation of this can be applied today. There are clearly established roles for genomic testing for some patients with CKD, largely those with suspected heritable forms, with these continuing to expand as new evidence emerges.
Novel Identification of Myeloid-Derived Suppressor Cells in Children With Septic Shock
Authors: Bline Katherine E. , Muszynski Jennifer A. , Guess Adam J. , Menocha Somaang , Moore-Clingenpeel Melissa D. , Popelka Jill K. , Hensley Josey M. , Steele Lisa M. , Goldthwaite Ian C. , Jedreski Kathleen J. , Hall Mark W.
Published: September 2022

OBJECTIVES:

Immunoparalysis in children with septic shock is associated with increased risk of nosocomial infections and death. Myeloid-derived suppressor cells (MDSCs) potently suppress T cell function and may perpetuate immunoparalysis. Our goal was to test the hypothesis that children with septic shock would demonstrate increased proportions of MDSCs and impaired immune function compared with healthy controls.

DESIGN:

Prospective observational study.

SETTING:

Fifty-four bed PICU in a quaternary-care children’s hospital.

PATIENTS:

Eighteen children with septic shock and thirty age-matched healthy children.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and stained for cell surface markers to identify MDSCs by flow cytometric analysis, including granulocytic and monocytic subsets. Adaptive and innate immune function was measured by ex vivo stimulation of whole blood with phytohemagglutinin-induced interferon (IFN) γ production and lipopolysaccharide (LPS)–induced tumor necrosis factor (TNF)–α production, respectively. Prolonged organ dysfunction (OD) was defined as greater than 7 days. Children with septic shock had a higher percentage of circulating MDSCs, along with lower LPS-induced TNFα and phytohemagglutinin-induced IFNγ production capacities, compared with healthy controls. A cut-off of 25.2% MDSCs of total PBMCs in initial samples was optimal to discriminate children with septic shock who went on to have prolonged OD, area under the curve equal to 0.86. Children with prolonged OD also had decreased TNFα production capacity over time compared with those who recovered more quickly (p = 0.02).

CONCLUSIONS:

This article is the first to describe increased MDSCs in children with septic shock, along with an association between early increase in MDSCs and adverse OD outcomes in this population. It remains unclear if MDSCs play a causative role in sepsis-induced immune suppression in children. Additional studies are warranted to establish MDSC as a potential therapeutic target.
Risk Factors for CSF/Plasma HIV-1 RNA Discordance in HIV-Infected Patients
Authors: Nie Jingmin , Zeng Yanming , Zeng Qingling , Du Xiang , Chen Yaokai
Published: September 2022

Background:

Few large investigations have evaluated the association of cerebrospinal fluid/plasma (CSF/plasma) discordance with opportunistic neurological infections. We aimed to determine risk factors for CSF/plasma discordance to further assess whether CSF/plasma discordance is associated with antiretroviral therapy (ART) and opportunistic neurological infections.

Methods:

A retrospective study was conducted based on HIV RNA viral load and associated risk factors in plasma and CSF samples from 491 HIV-infected patients. HIV RNA levels higher in CSF compared with plasma was defined as CSF/plasma discordance.

Results:

In this study, the rate of CSF/plasma discordance was 18.3%. We observed that headache, cryptococcal antigen, CSF cell count, Treponema pallidum particle assay positivity, and ART use were significantly associated with CSF/plasma discordance in the multivariate logistic regression model. The CSF RNA/plasma RNA ratio was significantly higher in HIV-infected patients with neurological infections than in HIV-infected cases without neurological infections (P < 0.001). CSF/plasma discordance was significantly different between HIV-infected patients without central nervous system (CNS) infection and those with CNS infection, tuberculous meningitis, cryptococcal meningitis, and neurosyphilis (P < 0.05).

Conclusions:

ART and CNS inflammation may influence CSF/plasma discordance.
Efficacy and Safety of a Simplified Lamivudine Plus Dolutegravir Dual Therapy in HIV-1–Infected Patients: A Multicenter Cohort Study in China
Authors: Zhong Mingli , Chen Chen , Hu Yue , Zou Meiyin , Yan Liting , Huang Jinlong , Lv Ru , Su Yifan , Qi Mingxue , Ye Zi , Pei Xueyu , Ma Ping , Wei Hongxia
Published: September 2022

Background:

Results from both clinical trials and real-world observational studies suggest that lamivudine plus dolutegravir (3TC + DTG) dual therapy has excellent virological efficacy and safety in HIV-1–infected patients. However, there is still no relevant study related to this dual therapy reported in China.

Methods:

In this multicenter, retrospective, observational study that included HIV-1–infected patients in China, baseline and follow-up data were collected to analyze the virological suppression rate, immune restoration, and adverse events during follow-up in HIV-1–infected patients who switched to the 3TC + DTG dual therapy.

Results:

This study recruited 112 HIV-1–infected patients, including 101 men (90.2%), with a median age of 44.0 years (IQR: 33.00–57.75) and median CD4+ T-cell count of 432.13 cells/μL (IQR: 237.75–578.50). The overall virological suppression rate was 94.5% at the 24-week follow-up. However, the virological suppression rates of men who have sex with men patients and patients with CD4+ T-cell count of <350 cells/μL were higher than the baseline value (P < 0.05) at week 24. The results of Cox regression analysis showed that the baseline CD4+ T-cell count was an independent determinant of immune restoration in patients, and patients with baseline CD4+ T-cell count of 350–500 cells/μL outperformed patients with baseline CD4+ T-cell count of <350 cells/μL in immune restoration (hazard ratio: 4.469, 95% confidence interval: 1.801 to 11.091, P = 0.001). Adverse events were reported in 5 patients (incidence rate of 4.5%); among them, 3 patients developed neuropsychiatric symptoms. Results from the laboratory data analysis showed that patients with grade 1 and 2 adverse events had elevated levels of low-density lipoprotein cholesterol and total bilirubin. Furthermore, grade 3 and 4 adverse events were associated with the elevation of blood glucose level in 4 patients.

Conclusions:

Thus, the 3TC + DTG dual therapy displayed an excellent virological efficacy against HIV-1 infections and had an acceptable safety profile, with predominantly mild adverse events in HIV-1–infected patients in China.
Tapered, Sand-Blasted, Large-Grit, and Acid-Etched Surfaced Internal Dental Implant in the Diverse Pathologic Jaw
Authors: Mustakim Kezia Rachellea , Han Jeong Joon , Eo Mi Young , Kim Soung Min
Published: September 2022

Purpose:

The treatment of pathologic lesions in jaws either through conservative or radical approaches, frequently leads to a loss of teeth. As a result, patients will experience diminished masticatory and phonetic function as well as esthetic deficits. In this manuscript, we report multiple cases of successful implant rehabilitation after the conservative treatment of pathologic lesions in jaws utilizing allogeneic bone grafts and the installation of implant fixtures.

Materials and Methods:

In this study, we examined 8 patients with 8 different kinds of pathologic lesions in their jaws, who were treated with a conservative approach and rehabilitated with bone grafts and implant installations using internal dental implant type with tapered, sand-blasted, large-grit, acid-etched surfaces. Marginal bone loss was analyzed through radiograms, and the implant survival rates and graft outcome evaluations were recorded.

Results:

No significant difference was found in the mean marginal bone loss throughout the follow-up period. The survival rate of the implant and the success rate of graft were recorded as 100%.

Conclusions:

The results of this study suggest that conservative surgical management for pathologic lesions based on the understanding of the pathologies can be helpful for successful oral rehabilitation. In bone grafting, it is necessary to determine an appropriate timing and method considering the risk of recurrence and the vascularity of the recipient site. For subsequent implant placement, selecting an implant system suitable for the site of placement and placing it within 3 to 6 months after bone grafting can help the long-term maintenance of the grafted bone and dental implant.
Haplotype-resolved assemblies and variant benchmark of a Chinese Quartet
Authors: Jia Peng , Dong Lianhua , Yang Xiaofei , Wang Bo , Wang Tingjie , Lin Jiadong , Wang Songbo , Zhao Xixi , Xu Tun , Che Yizhuo , Dang Ningxin , Ren Luyao , Zhang Yujing , Wang Xia , Liang Fan , Wang Yang , Ruan Jue ,   The Quartet Project Team, Zheng Yuanting , Shi Leming , Wang Jing , Ye Kai
Published: September 2022

As the state-of-the-art sequencing technologies and computational methods enable investigation of challenging regions in the human genome, an update variant benchmark is demanded. Herein, we sequenced a Chinese Quartet, consisting of two monozygotic twin daughters and their biological parents, with multiple advanced sequencing platforms, including Illumina, BGI, PacBio, and Oxford Nanopore Technology. We phased the long reads of the monozygotic twin daughters into paternal and maternal haplotypes using the parent-child genetic map. For each haplotype, we utilized advanced long reads to generate haplotype-resolved assemblies (HRAs) with high accuracy, completeness, and continuity. Based on the ingenious quartet samples, novel computational methods, high-quality sequencing reads, and HRAs, we established a comprehensive variant benchmark, including 3,883,283 SNVs, 859,256 Indels, 9,678 large deletions, 15,324 large insertions, 40 inversions, and 31 complex structural variants shared between the monozygotic twin daughters. In particular, the preciously excluded regions, such as repeat regions and the human leukocyte antigen (HLA) region, were systematically examined. Finally, we illustrated how the sequencing depth correlated with thede novoassembly and variant detection, from which we learned that 30 × HiFi is a balance between performance and cost. In summary, this study provides high-quality haplotype-resolved assemblies and a variant benchmark for two Chinese monozygotic twin samples. The benchmark expanded the regions of the previous report and adapted to the evolving sequencing technologies and computational methods.
Cocaine addiction-like behaviors are associated with long-term changes in gene regulation, energy metabolism, and GABAergic inhibition within the amygdala
Authors: Zhou Jessica L. , Guglielmo Giordano de , Ho Aaron J. , Kallupi Marsida , Pokhrel Narayan , Li Hai-Ri , Chitre Apurva S. , Munro Daniel , Mohammadi Pejman , Carrette Lieselot LG , George Olivier , Palmer Abraham A. , McVicker Graham , Telese Francesca
Published: September 2022

The amygdala processes positive and negative valence and contributes to the development of addiction, but the underlying cell type-specific gene regulatory programs are unknown. We generated an atlas of single nucleus gene expression and chromatin accessibility in the amygdala of outbred rats with low and high cocaine addiction-like behaviors following prolonged abstinence. Between rats with different addiction indexes, we identified thousands of cell type-specific differentially expressed genes enriched for energy metabolism-related pathways that are known to affect synaptic transmission and action potentials. Rats with high addiction-like behaviors showed enhanced GABAergic transmission in the amygdala, which, along with relapse-like behaviors, were reversed by inhibition of Glyoxalase 1, which metabolizes the GABAAreceptor agonist methylglyoxal. Finally, we identified thousands of cell type-specific chromatin accessible sites and transcription factor (TF) motifs where accessibility was associated with addiction index, most notably at motifs for pioneer TFs in the Fox, Sox, helix-loop-helix, and AP1 families.
High-throughput TCRB enrichment sequencing of human cord blood exhibited a distinct fetal T cell repertoire in the third trimester of pregnancy
Authors: Dong Yan , Chen Wei , Wang Jinmin , Wu Xiaolei , Zhao Yangyu , Cai Yuhang , Han Yingxin , Wang Yuqi , Li Hongmei , Qiao Jie , Wei Yuan
Published: September 2022

Study question

What are the molecular characteristics during the maturation process of the human fetal immune system in the third trimester of pregnancy?

Summary answer

Both the diversity and length of complementarity determining region 3 (CDR3s) in the fetal TCRB repertoire were less than those of adult CDR3s, and the fetal CDR3 length increased with gestation weeks in late pregnancy.

What is known already

The adaptive immune system recognizes various pathogens based on a large repertoire of T-cell receptors (TCR repertoire), but the maturation dynamics of the fetal TCR repertoire in the third trimester are largely unknown. The CDR3is the most diversified segment in the T-cell receptor β chain (TCRB) that binds and recognizes the antigen.

Study design, size, and duration

This was a basic research to assess the composing characteristics of TCRBs in core blood and the dynamic pattern with fetal development in the third trimester of pregnancy.

Participants/materials, setting methods

High-throughput TCRB-enrichment sequencing was utilized to characterize the TCRB repertoire of cord blood at 24~38 weeks of gestational age (WGA) with nonpreterm fetuses and to investigate their difference compared with that of adult peripheral blood.

Main results and the role of chance

Compared to the adult control, the fetal TCRB repertoire had a 4.8-fold lower number of unique CDR3s, a comparable Shannon diversity index (p=0.7387), a lower mean top clone rate (p< 0.001) and a constrictive top 1000 unique clone rates. Although all kinds of TCRBV and TCRBJ genes present in adult CDR3s were identified in fetuses, nearly half of these fragments showed a significant difference in usage. Moreover, the fetal TCRB repertoire held a shorter CDR3 length, and the CDR3 length showed a progressive increase with fetal development. Jensen–Shannon (JS) divergences of TCRBV and TCRBJ gene usage in dizygotic twins were much lower than those in unrelated pairs. In the parental-fetal pair, JS divergence of TCRBV gene usage was not obviously different, while that of TCRBJ gene usage was only slightly lower.

Limitations, reasons for caution

The sample size is limited due to the limited accessibility to cord blood in late pregnancy with healthy nonpreterm fetuses.

Wider implications of the findings

Our findings reveal the unique properties of fetal TCRB repertoires in the third trimester, fill the gap in our understanding of the maturation process of prenatal fatal immunity, and deepen our understanding of the immunologically relevant problems in neonates.

Study funding/competing interest(s)

This work was supported by the National Natural Science Foundation of China (82171661) and Tianjin Municipal Science and Technology Special Funds for Enterprise Development (NO. 14ZXLJSY00320). The authors declare that they have no competing interests.
Near-anoxia induces immobilisation and sustains viability of sperm in ant queens: Novel insights into mechanisms of prolonged sperm storage
Authors: Gotoh Ayako , Takeshima Mika , Mizutani Ken-ichi
Published: September 2022

Insect females store sperm in a spermatheca after copulation for some duration to use it later for fertilisation. At the beginning of their adult lives, ant queens can preserve numerous viable sperm cells from copulation for over ten years. However, the key factors influencing long-term sperm storage have not been identified. Here we show that the spermathecal environment is near anoxic, which induces sperm immobilisation. Furthermore, mitochondrial respiratory inhibitors suppress sperm motility, suggesting that sperm immobilisation may be caused by a shortage of ATP generated from only glycolysis under near anoxic condition. Sperm immobilisation is not induced by acidification via glycolytic metabolism because the spermathecal fluid is not acidic. Finally, we show that artificial anoxic conditions rather than aerobic conditions sustain viable sperm cells. Therefore, near-anoxia is a key factor influencing long-term sperm storage in ant queens. The viability of sperm cells under artificial anoxia, however, is lower than of those dissected immediately from queens. Moreover, the immotile sperm cells under more than 4 h of anoxia do not begin swimming after aerobic exposure, unlike those that were in anoxic conditions for less than 2 h. This indicates that factors other than anoxia are also necessary for long-term sperm preservation.
A common humanMLKLpolymorphism confers resistance to negative regulation by phosphorylation
Authors: Garnish Sarah E. , Martin Katherine R. , Kauppi Maria , Jackson Victoria , Ambrose Rebecca , Eng Vik Ven , Chiou Shene , Meng Yanxiang , Frank Daniel , Tovey Crutchfield Emma C. , Patel Komal M. , Jacobsen Annette V. , Atkin-Smith Georgia K. , Rago Ladina Di , Doerflinger Marcel , Horne Christopher R. , Hall Cathrine , Young Samuel N. , Athanasopoulos Vicki , Vinuesa Carola G. , Lawlor Kate E. , Wicks Ian P. , Ebert Gregor , Ng Ashley P. , Slade Charlotte A. , Pearson Jaclyn S. , Samson Andre L. , Silke John , Murphy James M. , Hildebrand Joanne M.
Published: September 2022

Across the globe, 2-3% of humans carry thep.Ser132Prosingle nucleotide polymorphism inMLKL, the terminal effector protein of the inflammatory form of programmed cell death, necroptosis. We show that this substitution confers a gain in necroptotic function in human cells, with more rapid accumulation of activated MLKLS132Pin biological membranes and MLKLS132Poverriding pharmacological and endogenous inhibition of MLKL. In mouse cells, the equivalentMlkl S131Pmutation confers a gene dosage dependent reduction in sensitivity to TNF-induced necroptosis in both hematopoietic and non-hematopoietic cells, but enhanced sensitivity to IFN-β induced death in non-hematopoietic cells.In vivo,MlklS131Phomozygosity reduces the capacity to clearSalmonellafrom major organs and retards recovery of hematopoietic stem cells. Thus, by dysregulating necroptosis, the S131P substitution impairs the return to homeostasis after systemic challenge. Present day carriers of theMLKL S132Ppolymorphism may be the key to understanding how MLKL and necroptosis modulate the progression of complex polygenic human disease.