bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurocognitive function and survival in children with average-risk medulloblastoma treated with hyperfractionated radiation therapy alone: Long-term mature outcomes of a prospective study
Authors: Gupta Tejpal , Kalra Babusha , Goswami Savita , Deodhar Jayita , Rane Pallavi , Epari Sridhar , Moiyadi Aliasgar , Dasgupta Archya , Chatterjee Abhishek , Chinnaswamy Girish
Published: March 2022

Background

The purpose of this study was to report long-term neurocognitive and clinical outcomes in children treated for average-risk medulloblastoma with hyperfractionated radiation therapy (HFRT) alone.

Methods

Between 2006 and 2010, 20 children with rigorously staged average-risk medulloblastoma were treated on a prospective study with HFRT without upfront adjuvant systemic chemotherapy after written informed consent. HFRT was delivered as twice-daily fractions (1 Gy/fraction, 6–8 hours apart, 5 days/week) to craniospinal axis (36 Gy/36 fractions) plus conformal tumor-bed boost (32 Gy/32 fractions). Neurocognitive function was assessed at baseline and periodically on follow-up using age-appropriate intelligence quotient (IQ) scales.

Results

Median age was 8 years (range 5–14 years) with 70% being males. Mean and standard deviation (SD) scores at baseline were 90.5 (SD = 17.08), 88 (SD = 16.82) and 88 (SD = 17.24) for Verbal Quotient (VQ), Performance Quotient (PQ), and Full-Scale IQ (FSIQ) respectively. Mean scores remained stable in the short-to-medium term but declined gradually beyond 5 years with borderline statistical significance for VQ (P = .042), but nonsignificant decline in PQ (P = .259) and FSIQ (P = .108). Average rate of neurocognitive decline was <1 IQ point per year over a 10-year period. Regression analysis stratified by age, gender, and baseline FSIQ failed to demonstrate any significant impact of the tested covariates on longitudinal neurocognitive function. At a median follow-up of 145 months, 10-year Kaplan-Meier estimates of progression-free survival and overall survival were 63.2% and 74.1% respectively.

Conclusion

HFRT alone without upfront adjuvant chemotherapy in children with average-risk medulloblastoma is associated with modest decline in neurocognitive functioning with acceptable long-term survival outcomes and may be most appropriate for resource-constrained settings.
Corticosteroids use and neurocognitive functioning in patients with recurrent glioblastoma: Evidence from European Organization for Research and Treatment of Cancer (EORTC) trial 26101
Authors: Caramanna Ivan , de Kort Julie M , Brandes Alba A , Taal Walter , Platten Michael , Idbaih Ahmed , Frenel Jean Sebastien , Wick Wolfgang , Preetha Chandrakanth Jayachandran , Bendszus Martin , Vollmuth Philipp , Reijneveld Jaap C , Klein Martin
Published: March 2022

Background

In patients with recurrent glioblastoma, corticosteroids are frequently used to mitigate intracranial pressure and to improve patient neurological functioning. To date, in these patients, no systematic studies have been performed to assess neurocognitive functioning (NCF) in relation to corticosteroid treatment.

Methods

Using baseline data (ie, prior to randomization) of European Organization for Research and Treatment of Cancer (EORTC) trial 26101, we performed regression analysis to assess the predictive value of corticosteroid intake on performance of the EORTC brain tumor clinical trial NCF test battery. The battery is comprised of the Hopkins Verbal Learning Test—Revised (HVLT-R), Controlled Oral Word Association Test (COWA), and Trail Making Test (A and B).

Results

Out of 321 patients, 148 (46.1%) were not using corticosteroids, and 173 were using dexamethasone (34.3%), methylprednisolone (9.7%), or other corticosteroids (9.9%). Patients on corticosteroids had worse performance on all neurocognitive tests. Regression analyses demonstrated a negative association between corticosteroids use and the HVLT-R free recall score (R2 change = 0.034, F change (1, 272) = 13.392, P < .001) and HVLT-R Delayed Recall score (R2 change = 0.028, F change (1, 270) = 10.623, P = .002). No statistically significant association was found for HVLT-R Delayed recognition, COWA, TMT part A and TMT part B (P > .05).

Conclusions

Glioblastoma patients prescribed with corticosteroids show poorer memory functions, expressive language, visual-motor scanning speed, and executive functioning than patients not using corticosteroids. Furthermore, we found a negative association between corticosteroid intake and memory functions. The possibility of deleterious effects of corticosteroids on NCF should be considered during clinical decision making.
Clinical Outcomes in Hospitalized Vaccine-Breakthrough Coronavirus Disease 2019 Cases Compared With Contemporary Unvaccinated Hospitalized Adults
Authors: Wolff Marcelo , Gilabert Margarita , Hernández Rodrigo
Published: March 2022

The inactivatedsevere acute respiratory syndrome coronavirus 2 vaccine (CoronaVac) has been the principal vaccine used in Chile’s prebooster immunization campaign. We compared major outcomes in 206 hospitalized vaccinated adults vs 507 unvaccinated adults (mid-2021). Individuals in the vaccinated group were much older, required less critical care, had lower mortality (adjusted by age), and had shorter hospitalization than those in the unvaccinated group. Benefits were most pronounced in those ≥60years of age.
Platinum-Group Element Geochemistry and Magma Evolution of the Mount Hagen (Papua New Guinea) Magmatic System
Authors: Misztela M A , Campbell I H , Arculus R J
Published: March 2022

Mount Hagen is a mid-Pleistocene stratovolcano located in the Papua New Guinea Highlands. It was selected for this study because of (1) its close location to several giant Cu–Au porphyry deposits in the region; (2) its high-K calc-alkaline character (absarokite–shoshonite) and (3) its wide compositional range (2 to 12 wt % MgO). Whole-rock geochemistry, petrography and QEMSCAN observations are consistent with fractional crystallisation of the evolving magma being controlled by the phases now represented by the megacrysts in the lavas: olivine and clinopyroxene at high MgO and hornblende and plagioclase at low MgO. However, the role of plagioclase is enigmatic. Although it is an abundant megacryst phase in the low-MgO samples, plagioclase has little or no influence on fractional crystallisation, suggesting that it may be an antecryst. The appearance of plagioclase megacrysts does not slow the rate of increase in Al2O3 or Sr with decreasing sample MgO and the low-MgO samples do not have Eu anomalies. At ~5.5 wt % MgO, there are significant changes in the system that are inconsistent with simple fractional crystallisation. These changes include hornblende and plagioclase replacing olivine and clinopyroxene as the principal megacryst phases, a sharp rise in platinum-group elements (PGE) concentrations, the brief reappearance of high Fo olivine megacrysts and reversed zoning in the plagioclase megacrysts. These changes are interpreted to have resulted from a new pulse of magma entering the system, with higher water, MgO, SiO2 and PGE concentrations than the original parent magma. Scatter in the PGE data is attributed to the presence of micronuggets in all samples, including the most mafic samples. We conclude that the magma system became sulphide saturated during an early stage in its fractionation history, probably before leaving the crust to deep crustal magma chamber, and then became undersaturated as a consequence of decreasing pressure as magma ascended into a mid-crustal magma chamber. The early saturation episode had a pronounced influence on PGE concentration but had little affect Cu and Au, due to their lower partition coefficient into sulphides. The magma became sulphide saturated again in the crustal magma chamber at ~8.5 wt % MgO, this time affecting all chalcophile elements. Given the early episodes of sulphide saturation, depletion in Au in the Mount Hagen magma system and the absence of a known porphyry system, it is unlikely that Mount Hagen produced economic porphyry mineralisation.
The Disparate Effect of Nudges on Minority Groups
Authors: Haran Rosen Maya , Sade Orly
Published: March 2022

We compare the effect of a text message sent to mobile phones on the actions of minority groups versus the general population in Israel. Using proprietary data from a dedicated survey, we show that the text message had an overall positive effect, but a significantly smaller effect on minority groups. We provide insights into potential channels (low digital literacy, low financial literacy, and low trust) that contribute to the differential effect. This evidence suggests that policy interventions relying on voluntary take-up by participants may be disproportionately taken up by nonmarginalized groups, an unintended effect that can exacerbate rather than mitigate disparities. (JEL D14, G38, G41, G51, G53, I38)
Sleep–wake states change the interictal localization of candidate epileptic source generators
Authors: McLeod Graham A , Abbasian Parandoush , Toutant Darion , Ghassemi Amirhossein , Duke Tyler , Rycyk Conrad , Serletis Demitre , Moussavi Zahra , Ng Marcus C
Published: March 2022

Study Objectives

To compare estimated epileptic source localizations from 5 sleep–wake states (SWS): wakefulness (W), rapid eye movement sleep (REM), and non-REM 1-3.

Methods

Electrical source localization (sLORETA) of interictal spikes from different SWS on surface EEG from the epilepsy monitoring unit at spike peak and take-off, with results mapped to individual brain models for 75% of patients. Concordance was defined as source localization voxels shared between 2 and 5 SWS, and discordance as those unique to 1 SWS against 1–4 other SWS.

Results

563 spikes from 16 prospectively recruited focal epilepsy patients across 161 day-nights. SWS exerted significant differences at spike peak but not take-off. Source localization size did not vary between SWS. REM localizations were smaller in multifocal than unifocal patients (28.8% vs. 54.4%, p = .0091). All five SWS contributed about 45% of their localizations to converge onto 17.0 ± 15.5% voxels. Against any one other SWS, REM was least concordant (54.4% vs. 66.9%, p = .0006) and most discordant (39.3% vs. 29.6%, p = .0008). REM also yielded the most unique localizations (20.0% vs. 8.6%, p = .0059).

Conclusions

REM was best suited to identify candidate epileptic sources. sLORETA proposes a model in which an “omni-concordant core” of source localizations shared by all five SWS is surrounded by a “penumbra” of source localizations shared by some but not all SWS. Uniquely, REM spares this core to “move” source voxels from the penumbra to unique cortex not localized by other SWS. This may reflect differential intra-spike propagation in REM, which may account for its reported superior localizing abilities.
Re-examining extreme sleep duration in bats: implications for sleep phylogeny, ecology, and function
Authors: Harding Christian D , Yovel Yossi , Peirson Stuart N , Hackett Talya D , Vyazovskiy Vladyslav V
Published: March 2022

Bats, quoted as sleeping for up to 20 h a day, are an often used example of extreme sleep duration amongst mammals. Given that duration has historically been one of the primary metrics featured in comparative studies of sleep, it is important that species specific sleep durations are well founded. Here, we re-examined the evidence for the characterization of bats as extreme sleepers and discuss whether it provides a useful representation of the sleep behavior of Chiroptera. Although there are a wealth of activity data to suggest that the diurnal cycle of bats is dominated by rest, estimates of sleep time generated from electrophysiological analyses suggest considerable interspecific variation, ranging from 83% to a more moderate 61% of the 24 h day spent asleep. Temperature-dependent changes in the duration and electroencephalographic profile of sleep suggest that bats represent a unique model for investigating the relationship between sleep and torpor. Further sources of intra-specific variation in sleep duration, including the impact of artificial laboratory environments and sleep intensity, remain unexplored. Future studies conducted in naturalistic environments, using larger sample sizes and relying on a pre-determined set of defining criteria will undoubtedly provide novel insights into sleep in bats and other species.
From dawn to dusk—mimicking natural daylight exposure improves circadian rhythm entrainment in patients with severe brain injury
Authors: Angerer Monika , Pichler Gerald , Angerer Birgit , Scarpatetti Monika , Schabus Manuel , Blume Christine
Published: March 2022

Study Objectives

While light therapy has proven effective in re-entraining circadian rhythms, the potential of such an intervention has not been evaluated systematically in post-comatose patients with disorders of consciousness (DOC), who often have strongly altered circadian rhythms.

Methods

We recorded skin temperature over 7–8 days in patients with DOC in each of two conditions: habitual light (HL), and dynamic daylight (DDL) condition. While patients were in a room with usual clinic lighting in the HL condition, they were in an otherwise comparable room with biodynamic lighting (i.e. higher illuminance and dynamic changes in spectral characteristics during the day) in the DDL condition. To detect rhythmicity in the patients’ temperature data, we computed Lomb–Scargle periodograms and analyzed normalized power, and peak period. Furthermore, we computed interdaily stability and intradaily variability, which provide information about rhythm entrainment and fragmentation.

Results

We analyzed data from 17 patients with DOC (i.e. unresponsive wakefulness syndrome [n = 15] and minimally conscious state [n = 2]). The period length of the patients’ temperature rhythms was closer to 24 h in the DDL as compared to the HL condition (median median deviation from 24 h: DDL = 0.52 h, HL = 3.62 h). Specifically, in 11/17 (65%) patients the period length was closer to 24 h in the DDL condition. Furthermore, the patients’ rhythm was more pronounced, more stable, and less variable in the DDL condition.

Conclusions

Our results indicate that DDL stimulation entrains and stabilizes circadian rhythms. This highlights the importance of adequate room lighting as an adjunct therapeutic approach for improving circadian rhythms in severely brain-injured patients.

Trial Registration Information

German Clinical Trials Register (DRKS00016041); registration: 18.01.2019; recording start: 04.06.2019 https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016041
Race, Gender, and Police Violence in the Shadow of Controlling Images
Authors: Remster Brianna , Smith Chris M , Kramer Rory
Published: March 2022

Despite the emergence of the #SayHerName movement alongside #BlackLivesMatter, research on police encounters is rarely intersectional and has largely neglected the potentially violent consequences of gendered and racialized “controlling images.” Using New York City investigatory stop data (2007–2014), and drawing on controlling images theory, our analysis shows that Black men and women experience higher rates of police violence than White men and women. Within race, analyses indicate that Black men experience more police violence than Black women. The same gender gap exists for Whites, Asians, and Latinx persons, suggesting that broad cultural perceptions of femininity and masculinity shape police violence. However, these gendered frames mostly dissolve in instances of potentially fatal violence, as we find no gender differences within race or ethnicity in these extreme cases with one exception: police point their guns at Black men slightly more than at Black women. Further, the controlling image criminalizing Black men casts a long shadow—police are more likely to use violence on individuals stopped in the company of a Black man across gender, race, and ethnicity. This study provides a comprehensive, intersectional analysis of police encounters, both reaffirming and extending controlling images to understand why race, ethnicity, and gender disparities in state violence experiences persist.
Sex-Related Differences in Postoperative Outcomes After Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis
Authors: Bozso Sabin J. , EL-Andari Ryaan , J.H. Kang Jimmy , Eckstein Janine , Nagendran Jeevan
Published: March 2022

Aortic stenosis is the most common valvular disease of the heart and is increasing in prevalence. Previous literature has found inferior outcomes for females undergoing surgical aortic valve replacement, while recent investigations have found equivalent or superior outcomes for females undergoing transcatheter aortic valve replacement (TAVR). PubMed and Medline were systematically searched for articles published from January 1, 2010, to April 30, 2021, for retrospective and prospective studies comparing outcomes between males and females undergoing TAVR. One thousand one hundred eighty titles and abstracts were screened, and 28 were included in this review. Risk of bias was assessed using questions derived from the ROBINS-I tool and previous literature. The data were compiled and analyzed using the RevMan 5.4 software. The results of this review confirm the previously published literature and have found rates of acute kidney injury (P = 0.05) and postoperative pacemaker insertion (P < 0.00001) favoring females and in-hospital mortality (P = 0.04), stroke (P < 0.00001), bleeding complications (P < 0.00001), and vascular complications (P < 0.00001) favoring males. The previously published literature has demonstrated consistently inferior outcomes for females undergoing heart valve surgery when compared to males. However, contemporary literature investigating sex differences after TAVR has found comparable outcomes for females. While the postoperative outcomes after surgical aortic valve replacement and TAVR are well established, the causal factors are still unidentified. Future studies utilizing matching based on preoperative characteristics and follow-up including collection of postoperative ventricular remodeling and prosthetic valve performance data will aid in elucidating the causal factors impacting outcomes for males and females after TAVR.
Applying the Value Transformation Framework in Federally Qualified Health Centers to Increase Clinical Measures Performance
Authors: Modica Cheryl , Bay Curt , Lewis Joy H. , Silva Camila
Published: March 2022

Introduction:

The transition in health care from a volume-based to value-based model of care, combined with pressures brought about by the COVID-19 pandemic, makes the need for efficiency and coordination of the health center system imperative. The Value Transformation Framework (VTF), developed with health centers in mind, provides an organizing framework to support transformation of infrastructure, care delivery, and people systems.

Methods:

NACHC applied the VTF within a cohort of health centers across the country to drive systems change and improve performance on measures of clinical care.

Results:

A comparison of health centers “participating” in application of the VTF relative to “nonparticipating” health centers nationally showed improvement during 3 years of program implementation. Significant differences (p < .05) favoring health centers who participated were noted for screening of colorectal cancer (p < .001), depression (p < .001), hypertension (p < .001), obesity (p = .001), and cervical cancer (p = .011). Performance for diabetes control also favored participating programs, although the difference did not quite reach significance (p = .45).

Conclusions:

Applying a systems approach, organized by the VTF, with evidence-based interventions and deployed in a learning community, can result in improved performance across multiple measures of clinical care.
Identifying large-scale recombination and capsular switching events in Streptococcus agalactiae strains causing disease in adults in the UK between 2014 and 2015
Authors: Khan Uzma Basit , Jauneikaite Elita , Andrews Robert , Chalker Victoria J. , Spiller Owen B.
Published: March 2022

Cases of invasive group B streptococcal infection in the adult UK population have steadily increased over recent years, with the most common serotypes being V, III and Ia, but less is known of the genetic background of these strains. We have carried out in-depth analysis of the whole-genome sequences of 193 clinically important group B

Streptococcus

(GBS) isolates (184 were from invasive infection, 8 were from non-invasive infection and 1 had no information on isolation site) isolated from adults and submitted to the National Reference Laboratory at the UK Health Security Agency between January 2014 and December 2015. We have determined that capsular serotypes III (26.9%), Ia (26.4%) and V (15.0%) were most commonly identified, with slight differences in gender and age distribution. Most isolates (n=182) grouped to five clonal complexes (CCs), CC1, CC8/CC10, CC17, CC19 and CC23, with common associations between specific serotypes and virulence genes. Additionally, we have identified large recombination events mediating potential capsular switching events between sequence type (ST)1 serotype V and serotypes Ib (n=2 isolates), II (n=2 isolates) and VI (n=2 isolates); between ST19 serotype III and serotype V (n=5 isolates); and between CC17 serotype III and serotype IV (n=1 isolate). The high genetic diversity of disease-causing isolates and multiple recombination events reported in this study highlight the need for routine surveillance of the circulating disease-causing GBS strains. This information is crucial to better understand the global spread of GBS serotypes and genotypes, and will form the baseline information for any future GBS vaccine research in the UK and worldwide.
Higher polygenic risk for melanoma is associated with improved survival
Authors: Seviiri Mathias , Scolyer Richard A. , Bishop D. Timothy , Iles Mark M. , Lo Serigne N. , Stretch Johnathan R. , Saw Robyn P.M. , Nieweg Omgo E. , Shannon Kerwin F. , Spillane Andrew J. , Gordon Scott D. , Olsen Catherine M. , Whiteman David C. , Landi Maria T. , Thompson John F. , Long Georgina V. , MacGregor Stuart , Law Matthew H.
Published: March 2022

Background

Although there are well-known prognostic factors for survival from cutaneous melanoma (CM) such as primary tumour thickness and stage of the tumour at diagnosis, the role of germline genetic factors in determining survival is not well understood.

Objective

To perform a genome-wide association study (GWAS) meta-analysis of melanoma-specific survival (MSS), and test whether a CM-susceptibility polygenic risk score (PRS) is associated with MSS.

Methods

We conducted two Cox proportional-hazard GWAS of MSS using data from the Melanoma Institute Australia (MIA; 5,762 patients with melanoma; 800 deaths from melanoma) and UK Biobank (UKB: 5,220 patients with melanoma; 241 deaths from melanoma). The GWAS were adjusted for age, sex and the first ten genetic principal components, and combined in a fixed-effects inverse-variance-weighted meta-analysis. Significant (P<5×10−8) results were investigated in the Leeds Melanoma Cohort (LMC; 1,947 patients with melanoma; 370 melanoma deaths). We also developed a CM-susceptibility PRS using a large independent GWAS meta-analysis (23,913 cases, 342,870 controls). The PRS was tested for an association with MSS in the MIA and UKB cohorts, with replication in the LMC.

Results

Two loci were significantly associated with MSS in the meta-analysis of MIA and UKB with lead SNPs rs41309643 (G allele frequency 1.6%, hazard ratio [HR] 2.09, 95% confidence interval [CI] 1.61-2.71, P=2.08×10−8) on chromosome 1, and rs75682113 (C allele frequency 1.8%, HR=2.38, 95% CI=1.77—3.21, P=1.07×10−8) on chromosome 7. While neither SNP replicated (P>0.05) in the LMC, rs75682113 was significantly associated in the combined discovery and replication sets and requires confirmation in additional cohorts.

After adjusting for age at diagnosis, sex and the first ten principal components, a one standard deviation increase in the CM-susceptibility PRS was associated with improved MSS in the discovery meta-analysis (HR=0.88, 95% CI=0.83—0.94, P=6.93×10−5; I2=88%). The association with the PRS was not replicated (P > 0.05) in LMC, but remained significantly associated with MSS in the meta-analysis of the discovery and replication results.

Conclusion

We found two loci potentially associated with MSS, and evidence that increased germline genetic susceptibility to develop CM may be associated with improved MSS.
MYB12 spatiotemporally represses TMO5/LHW-mediated transcription in the Arabidopsis root meristem
Authors: Wybouw Brecht , Arents Helena E. , Yang Baojun , Nolf Jonah , Smet Wouter , Vandorpe Michael , Van Damme Daniël , Glanc Matouš , De Rybel Bert
Published: March 2022

Transcriptional networks are crucial to integrate various internal and external signals into optimal responses during plant growth and development. Primary root vasculature patterning and proliferation are controlled by a network centred around the basic Helix-Loop-Helix transcription factor complex formed by TARGET OF MONOPTEROS 5 (TMO5) and LONESOME HIGHWAY (LHW), which control cell proliferation and orientation by modulating cytokinin response and other downstream factors. Despite recent progress, many aspects of the TMO5/LHW pathway are not fully understood. In particular, the upstream regulators of TMO5/LHW activity remain unknown. Here, using a forward genetic approach to identify new factors of the TMO5/LHW pathway, we discovered a novel function of the MYB-type transcription factor MYB12. MYB12 physically interacts with TMO5 and dampens the TMO5/LHW-mediated induction of direct target gene expression as well as the periclinal/radial cell divisions. The expression ofMYB12is activated by the cytokinin response, downstream of TMO5/LHW, resulting in a novel MYB12-mediated negative feedback loop that restricts TMO5/LHW activity to ensure optimal cell proliferation rates during root vascular development.
Rare Variants in Inborn Errors of Immunity Genes Associated with Covid-19 Severity
Authors: Liu Panhong , Fang Mingyan , Luo Yuxue , Zheng Fang , Jin Yan , Cheng Fanjun , Zhu Huanhuan , Jin Xin
Published: March 2022

Covid-19 is a contagious disease caused by SARS-CoV-2, a novel severe acute respiratory syndrome coronavirus. Common variants and networks underlying host genetic mechanisms have been extensively studied to identify disease-associated genetic factors. However, there are few studies about the rare variants, typically inborn errors of immunity, in understanding the host genetics behind Covid-19 infection, especially in the Chinese population. To fill this gap, we investigate likely-deleterious missense and high-confidence predicted loss-of-function variants by (a) performing gene- and pathway-level association analyses, (b) examining known genes involved in type I interferon signaling and others previously reported in Covid-19 disease, and (c) identifying candidate genes with accumulating mutations and their potential protein-protein interactions with known genes. Based on our analyses, several putative genes and pathways are uncovered and worth further investigation, for example, genes IL12RB1, TBK1, and TLR3, and pathways Tuberculosis (hsa:05152), Primary Immunodeficiency (hsa:05340), and Influenza A (hsa:05164). These regions generally play an essential role in regulating antiviral innate immunity responses to foreign pathogens and in responding to many inflammatory diseases. We believe that to some extent, as an acute inflammatory disease, Covid-19 is also affected by these inborn errors of immunity. We hope that the identification of these rare genetic factors will provide new insights into the genetic architecture of Covid-19.
SHERLOCK4HAT: a CRISPR-based tool kit for diagnosis of Human African Trypanosomiasis
Authors: Sima Núria , Dujeancourt-Henry Annick , Perlaza Blanca Liliana , Ungeheuer Marie-Noelle , Rotureau Brice , Glover Lucy
Published: March 2022

Elimination of Human African Trypanosomiasis (HAT) requires highly specific and sensitive tools for both diagnostic at point of care and epidemiological surveys. We have adapted SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) for the detection of trypanosome nucleic acids. Our SHERLOCK4HAT diagnostic tool kit, using 7SLRNA, TgSGP and SRA targets, distinguishes between Trypanosoma brucei (T. b.) brucei, T. b. gambiense (g) and T. b. rhodesiense (r) without cross-reactivity and with sensitivity between 0.01 and 0.1 parasite/µL. SHERLOCK4HAT can accurately detect a trypanosome infection in cryo-banked patient buffy coats, with 85.1% sensitivity and 98.4% specificity for gHAT, and 100% sensitivity and 94.1% specificity for rHAT. Our SHERLOCK4HAT diagnostic showed 85.6% correlation with a reference standard qPCR in gHAT patients, 96.2% correlation in rHAT patients, discriminates between r/gHAT with 100% accuracy and is compatible with lateral flow assay readout for use at the point of care.
The development of the Supplemental Nutrition Assistance Program enrollment accessibility (SNAP-Access) score
Authors: Samuel Laura J. , Xiao Emily , Cerilli Caroline , Sweeney Fiona , Campanile Jessica , Milki Nubaira , Smith Jared , Zhu Jiafeng , Yenokyan Gayane , Gherman Adi , Varadaraj Varshini , Swenor Bonnielin K.
Published: March 2022

Background

The Supplemental Nutrition Assistance Program (SNAP) is a federally funded public benefit providing critical food assistance to millions of Americans. However, it is typically administered by states, creating potential variation in accessibility and transparency of information about enrollment for people with disabilities.

Objective

To create a method to assess the accessibility and transparency of information about the disability-inclusive process and practices of SNAP enrollment

Methods

Data was collected from SNAP landing and enrollment webpages from all 50 U.S. states, the District of Columbia, and New York City from June-August 2021. Based on key principles of universal design and accessibility, scores were determined for each SNAP program across three areas: flexibility in the enrollment process (6 points), efficiency of finding information about enrollment on SNAP websites (6 points), and the accessibility of SNAP webpages (6 points). Total scores were the sum of these sub-categories (18 points maximum).

Results

Of the 52 SNAP programs assessed, mean scores were 10.66 (SD=2.51) for the total score, 2.67 (SD=0.91) for flexibility in the enrollment process, 3.32 (SD=1.19) for efficiency of finding information about enrollment on SNAP websites, and 4.67 (SD=1.72) for the accessibility of SNAP webpage. A total of 0 SNAP programs received the maximum score (6 points) on flexibility, 2 programs the maximum on efficiency, and 31 programs the maximum on accessibility.

Conclusions

We found differences in the accessibility, flexibility, and efficiency of SNAP program enrollment information available on SNAP websites and outline much room for improvement across all three of these areas.
Deciphering the heterogeneous niche in the tumor progression of hepatocellular carcinoma: a Spatial single-cell landscape and multi-omics atlas analysis
Authors: Ye Jiazhou , Lin Yan , Liao Zhiling , Gao Xing , Lu Cheng , Lu Lu , Huang Julu , Huang Xi , Bai Tao , Chen Jie , Wang Xiaobo , Luo Min , Xie Mingzhi , Wu Feixiang , Wu Guobin , Ma Liang , Xiang Bangde , Li Yongqiang , Yu Hongping , Luo Xiaoling , Liang Rong
Published: March 2022

Hepatocellular carcinoma (HCC) is an invasive disease which is characteristic with highly heterogeneous molecular phenotype, rich blood supply, and unique immune niche, therefore it is of great significance to explore the tumor heterogeneous niche and clonal evolution progress of these malignant cells. Based on the advance in single-cell technology, spatial transcriptome technology, and Oxford nanopore technology, this study innovatively reconstructed and delineated the heterogeneity of the HCC tumor niche and its tumor progression pattern. Our results showed that the copy number variation (CNV) of cells in cancer lesions and liver cirrhosis lesions of the same patient is basically the same and is mainly regulated by transcription factors such as TP53, HOXA7, FOXN3, and PPARG, suggests that malignant cells of common origin gradually evolve into different lesions in a very rare numbers of different CNVs, which are mainly regulated by expression patterns and mediate the heterogeneity between the tumor and cirrhosis lesions. Angiogenesis-related genes (SREBF1, ZNF585A, and HOXB5) may mediate communication between HCC subpopulations and endothelial cells via exosomes, thereby contributing to the angiogenic niche before HCC metastasis. In addition, numerous CNVs were found in patients with early recurrent HCC, and these mutated genes is the potential niche genes for the early tumor recurrence. In summary, this study provides a general transcriptional landscape of the ecological structure of HCC, systematically maps the molecular, cellular, and spatial composition of different HCC cell niches, and provides a scientific and theoretical basis at the molecular and cellular levels for personalized and accurate treatment strategies for HCC.
Seroneutralization of Omicron BA.1 and BA.2 in patients receiving anti-SARS-CoV-2 monoclonal antibodies
Authors: Bruel Timothée , Hadjadj Jérôme , Maes Piet , Planas Delphine , Seve Aymeric , Staropoli Isabelle , Guivel-Benhassine Florence , Porrot Françoise , Bolland William-Henry , Nguyen Yann , Casadevall Marion , Charre Caroline , Péré Hélène , Veyer David , Prot Matthieu , Baidaliuk Artem , Cuypers Lize , Planchais Cyril , Mouquet Hugo , Baele Guy , Mouthon Luc , Hocqueloux Laurent , Simon-Loriere Etienne , André Emmanuel , Terrier Benjamin , Prazuck Thierry , Schwartz Olivier
Published: March 2022

The SARS-CoV-2 Omicron BA.1 variant has been supplanted in many countries by the BA.2 sub-lineage. BA.2 differs from BA.1 by about 21 mutations in its spike. Human anti-spike monoclonal antibodies (mAbs) are used for prevention or treatment of COVID-19. However, the capacity of therapeutic mAbs to neutralize BA.1 and BA.2 remains poorly characterized. Here, we first compared the sensitivity of BA.1 and BA.2 to neutralization by 9 therapeutic mAbs. In contrast to BA.1, BA.2 was sensitive to Cilgavimab, partly inhibited by Imdevimab and resistant to Adintrevimab and Sotrovimab. Two combinations of mAbs, Ronapreve (Casirivimab + Imdevimab) and Evusheld (Cilgavimab + Tixagevimab), are indicated as a pre-exposure prophylaxis in immunocompromised persons at risk of severe disease. We analyzed sera from 29 such individuals, up to one month after administration of Ronapreve and/or Evusheld. After treatment, all individuals displayed elevated antibody levels in their sera and neutralized Delta with high titers. Ronapreve recipients did not neutralize BA.1 and weakly impaired BA.2. With Evusheld, neutralization of BA.1 and BA.2 was detected in 19 and 29 out of 29 patients, respectively. As compared to Delta, titers were more severely decreased against BA.1 (344-fold) than BA.2 (9-fold). We further report 4 breakthrough Omicron infections among the 29 participants. Therefore, BA.1 and BA.2 exhibit noticeable differences in their sensitivity to therapeutic mAbs. Anti-Omicron activity of Ronapreve, and to a lesser extent that of Evusheld, is reduced in patients’ sera, a phenomenon associated with decreased clinical efficacy.
The effect of focused muscle contraction therapy on chronic pain and Brodmann Area activity in former National Football League players
Authors: Cohen Neli , Hachaj Greg , Rubio Jose , Kastelz Alexandra , Hachaj Marcin , Zierfuss Dan , Osman Maab , Tsiampas Pete , Fernhall Bo , Velis Effrossyni Votta , Benedetti Enrico , Bartholomew Amelia
Published: March 2022

NFL players have a traumatic injury rate approaching 100%; chronic pain with decreased concentration occur commonly. This study examined the role of a novel focused muscle contraction therapy for the treatment of chronic pain and identified its impact on brain activity. Chronic pain was assessed by numerical score, neuropathic component, and impact on daily activities in 8 retired players. Brain activity was characterized by QEEG with low-resolution electromagnetic tomography analysis and functional measures of visual and auditory attention. Focused muscle contraction muscle therapy administered twice weekly for 6 months was tapered to twice monthly by 12 months. Brodmann Areas (BA) 4 and 9, known to associate with chronic pain, showed values outside the clinically normal range; mean pain duration was 16.5 ± 12.9 years. At 6 months, 5/8 subjects reported pain scores of 0. High beta wave activity was seen in BA 19, 21, 29, 30, and 39, affecting auditory, visual, and body perceptions. Clinically relevant improvements were observed in auditory attention and visual stamina. Pain relief was sustained through 18 months of follow-up. Focused muscle contraction therapy appears to redirect brain activity to new areas of activity which are associated with long-lasting relief of chronic pain and its detriments. This study was registered with clinicaltrial.gov #NCT04822311.
Evidence for SARS-CoV-2 Delta and Omicron co-infections and recombination
Authors: Bolze Alexandre , Basler Tracy , White Simon , Rossi Andrew Dei , Wyman Dana , Roychoudhury Pavitra , Greninger Alexander L. , Hayashibara Kathleen , Beatty Mark , Shah Seema , Stous Sarah , Kil Eric , Dai Hang , Cassens Tyler , Tsan Kevin , Nguyen Jason , Ramirez Jimmy , Carter Scotty , Cirulli Elizabeth T. , Barrett Kelly Schiabor , Washington Nicole L. , Belda-Ferre Pedro , Jacobs Sharoni , Sandoval Efren , Becker David , Lu James T. , Isaksson Magnus , Lee William , Luo Shishi
Published: March 2022

Between November 2021 and February 2022, SARS-CoV-2 Delta and Omicron variants co-circulated in the United States, allowing for co-infections and possible recombination events. We sequenced 29,719 positive samples during this period and analyzed the presence and fraction of reads supporting mutations specific to either the Delta or Omicron variant. We identified 18 co-infections, one of which displayed evidence of a low Delta-Omicron recombinant viral population. We also identified two independent cases of infection by a Delta-Omicron recombinant virus, where 100% of the viral RNA came from one clonal recombinant. In the three cases, the 5’-end of the viral genome was from the Delta genome, and the 3’-end from Omicron including the majority of the spike protein gene, though the breakpoints were different. Delta-Omicron recombinant viruses were rare, and there is currently no evidence that Delta-Omicron recombinant viruses are more transmissible between hosts compared to the circulating Omicron lineages.
Knowledge, attitudes, and positions of religious leaders towards female genital mutilation: A cross-sectional study from the Kurdistan Region of Iraq
Authors: Mahmood Kazhan I. , Shabu Sherzad A. , M-Amen Karwan , Saleh Abubakir M. , Ahmed Hamdia , Mzori Barzhang Q. , Shabila Nazar P.
Published: March 2022

Background

Understanding the perspectives of the key players in the community regarding female genital cutting (FGC) is very important for directing preventive programs. Religious leaders help shape community behaviors, which is highly pertinent in the case of FGC as it is frequently perceived to be a religious requirement. This study assesses religious leaders’ knowledge, attitudes, and positions towards FGC in the Kurdistan Region of Iraq.

Methods

This cross-sectional study was conducted in the Kurdistan Region of Iraq. It included a purposive sample of 147 local religious leaders (khateebs) representing the three governorates of Erbil, Sulaimaniyah, and Duhok. A self-administered questionnaire was used to collect data about the religious leaders’ knowledge, attitude, and position towards FGC.

Results

The participants identified reduction of the sexual desire of women as the main benefit (37%) and risk (24%) of FGC. Cultural tradition and religious requirements were the main reasons for practicing FGC. About 59% of the religious leaders stated that people ask for their advice on FGC. Around 14% of the participants supported performing FGC, compared to 39.1% who opposed it. Religious (73.9%) and cultural (26.1%) rationales were the main reasons given for supporting FGC. Being a cultural practice and having harmful effects (53.5%) and lack of clear religious evidence (46.6%) were the main reasons for being against FGC. Around 52% of the participants recommended banning FGC by law, while 43.5% did not support banning it. A statistically significant association (P=0.015) was found between religious leaders’ residence and their position on performing FGC. More than 46% of those residing in Duhok were against performing FGC, compared to lower proportions in Erbil (38.8%) and Sulaimaniyah (30%).

Conclusion

A conclusive decision concerning FGC banning needs to be made by religious authorities to advise people to avoid the practice. Health awareness activities incorporating FGC risks should be carried out to enlighten religious leaders at different levels of religious positions. Further research exploring perspectives of religious authorities concerning religious leaders’ inconclusive judgments about FGC is deemed necessary.
Afucosylation of HLA-specific IgG1 as a potential predictor of antibody pathogenicity in kidney transplantation
Authors: Bharadwaj Pranay , Shrestha Sweta , Pongracz Tamas , Concetta Catalano , Sharma Shilpee , Le Moine Alain , de Haan Noortje , Murakami Naoka , Riella Leonardo V. , Holovska Vanda , Wuhrer Manfred , Marchant Arnaud , Ackerman Margaret E.
Published: March 2022

Antibody-mediated rejection (AMR) is the leading cause of graft failure. While donor-specific antibodies (DSA) are associated with a higher risk of AMR, not all patients with DSA develop rejection suggesting that the characteristics of alloantibodies that determine their pathogenicity remain undefined. Using human leukocyte antigen (HLA)-A2-specific antibodies as a model, we applied systems serology tools to investigate qualitative features of immunoglobulin G (IgG) alloantibodies including Fc-glycosylation patterns and FcγR binding properties. The levels of afucosylation of anti-A2 antibodies were elevated in all seropositive patients and were significantly higher in AMR patients, suggesting potential cytotoxicity via FcγRIII-mediated mechanisms. Afucosylation of both glycoengineered monoclonal and naturally glycovariant polyclonal serum IgG specific to HLA-A2 exhibited potentiated binding to, slower dissociation from, and enhanced signaling through FcγRIII, a receptor widely expressed on innate effector cells. Collectively, these results suggest that afucosylated DSA may be a biomarker of AMR and could contribute to its pathogenesis.
Graphical Abstract.

Potential influence of HLA-A2-specific IgG1 afucosylation, FcγRIIIa binding and activation on ADCC and graft rejection.

Illustration created with https://BioRender.com.
FHIR “Profiliferation”: A Data Science Approach
Authors: Kramer Mark A.
Published: March 2022

Profiling is a mechanism for shaping Fast Healthcare Interoperability Resources (FHIR) for particular use cases. “Profiliferation” (profile + proliferation) is a coinage referring to the explosive growth in the number of FHIR profiles over the past few years. By reviewing a broad sample of almost 3000 FHIR profiles from 125 implementation guides, it was determined that just two items, Observation and Extension, accounted for half the profiles. FHIR’s 80/20 rule was determined to be closer to 65/35, revealing that FHIR is more dependent on profiling than initially intended. Use of the Observation resource was inconsistent, hinting that the resource is either poorly designed, or that users lack proper guidance. Better management of reusable items and certain changes in FHIR and profiling practices could improve the consistency of FHIR artifacts and reduce unnecessary and potentially incompatible profiles.
Disentangling the effect of measures, variants and vaccines on SARS-CoV-2 Infections in England: A dynamic intensity model
Authors: Boldea Otilia , Cornea-Madeira Adriana , Madeira Joao
Published: March 2022

In this paper, we estimate the path of daily SARS-CoV-2 infections in England from the beginning of the pandemic until the end of 2021. We employ a dynamic intensity model, where the mean intensity conditional on the past depends both on past intensity of infections and past realised infections. The model parameters are time-varying and we employ a multiplicative specification along with logistic transition functions to disentangle the time-varying effects of non-pharmaceutical policy interventions, of different variants and of protection (waning) of vaccines/boosters. We show that earlier interventions and vaccinations are key to containing an infection wave. We consider several scenarios that account for more infectious variants and different protection levels of vaccines/boosters. These scenarios show that, as vaccine protection wanes, containing a new wave in infections and an associated increase in hospitalisations in the near future will require further booster campaigns and/or non-pharmaceutical interventions.
Long COVID and its associated factors among COVID survivors in the community from a middle-income country – an online cross-sectional study
Authors: Moy Foong Ming , Hairi Noran Naqiah , Jian Lim Eugene Ri , Bulgiba Awang
Published: March 2022

Introduction

Patients with COVID-19 usually recover and return to normal health, however some patients may have symptoms that last for weeks or even months after recovery. This persistent state of ill health is known as Long COVID if it continues for more than 12 weeks and are not explained by an alternative diagnosis. Long Covid has been overlooked in low and middle income countries. Therefore, we conducted an online survey among the COVID-19 survivors in the community to explore their Long COVID symptoms, factors associated with Long COVID and how Long COVID affected their work.

Methods

This was a cross sectional study conducted from July to September 2021, during the implementation of a nationwide movement control order (MCO). Data was collected using the REDCap electronic data capture tool. The questionnaire was distributed in social and news media. The questionnaire covers information such as socio-demographic characteristics, existing comorbidities, self-perception on health, information on the acute COVID-19 condition and treatment received, symptoms and duration of post-COVID condition and effects on occupation. Results: A total of 732 COVID-19 survivors responded. There were slightly more females (58.7%), younger and more highly educated respondents. More than half of them were overweight or obese and about two third were free of comorbidities. Among these respondents, about 56% were without or with mild symptoms during their acute COVID-19 conditions. A total of 21.1% of the respondents reported to experience Long COVID. The most commonly reported symptoms for Long COVID were fatigue, brain fog, depression, anxiety, insomnia, arthralgia or myalgia. Females had 58% higher odds (95% CI: 1.02, 2.45) of experiencing Long COVID. Patients with moderate and severe levels of acute COVID-19 symptoms had OR of 3.01 (95% CI: 1.21, 7.47) and 3.62 (95% CI: 1.31, 10.03) respectively for Long COVID.

Conclusion

This study provides additional insight on the symptoms and duration of post-COVID symptoms as well as the associated factors with Long COVID among COVID-19 survivors in Malaysia. Recognition of Long COVID and its associated factors is important in planning prevention, rehabilitation, clinical management to improve recovery and long-term COVID-19 outcomes.