bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidural stimulation of the cervical spinal cord improves voluntary motor control in post-stroke upper limb paresis
Authors: Powell Marc P. , Verma Nikhil , Sorensen Erynn , Carranza Erick , Boos Amy , Fields Daryl , Roy Souvik , Ensel Scott , Barra Beatrice , Balzer Jeffery , Goldsmith Jeff , Friedlander Robert M. , Wittenberg George , Fisher Lee E. , Krakauer John W , Gerszten Peter C. , Pirondini Elvira , Weber Douglas J , Capogrosso Marco
Published: April 2022

A large proportion of cerebral strokes disrupt descending commands from motor cortical areas to the spinal cord which can results in permanent motor deficits of the arm and hand1,2. However, below the lesion, the spinal circuits that control movement5remain intact and could be targeted by neurotechnologies to restore movement6–9. Here we demonstrate that by engaging spinal circuits with targeted electrical stimulation we immediately improved voluntary motor control in two participants with chronic post-stroke hemiparesis. We implanted a pair of 8-contact percutaneous epidural leads on the lateral aspect of the cervical spinal cord to selectively target the dorsal roots that provide excitatory inputs to motoneurons controlling the arm and hand10,11. With this strategy, we obtained independent activation of shoulder, elbow and hand muscles. Continuous stimulation through selected contacts at specific frequencies enabled participants to perform movements that they had been unable to perform for many years. Overall, stimulation improved strength, kinematics, and functional performance. Unexpectedly, both participants retained some of these improvements even without stimulation, suggesting that spinal cord stimulation could be a restorative as well as an assistive approach for upper limb recovery after stroke.
Effectiveness of a psychosocial training intervention in reducing psychological distress among caregivers of intellectually disabled children in Malawi – a randomized wait-list trial
Authors: Masulani-Mwale C. , Kauye F. , Gladstone M
Published: April 2022

Background

Rates of disability are high in resource-poor settings with eighty-five percent of disabled children living in these settings. Long-term caregiving for disabled children is associated with fatigue, financial difficulties, parenting distress, and other psychological issues. Studies have shown a link between parenting children with intellectual disabilities and psychological distress as well as overall Health-Related Quality of Life (QoL). However, with interventions, these negative impacts may not be as severe as thought before. This study aimed at developing and testing the impact of a contextualized psychological intervention, Titukulane, in reducing psychological distress among caregivers with intellectually disabled children in Malawi.

Methods

We conducted a randomized waitlist trial of a psychosocial training intervention (Titukulane) provided to caregivers of children with intellectual disabilities. Caregivers of children with intellectual disabilities aged 0 to 18 years were recruited, screened, and then enrolled in the trial through two disability organizations operating in Mzuzu (St John of God) and Lilongwe (Children of Blessings). They were then randomized in blocks to the Titukulane intervention or waitlist and provided with the intervention or standard care for 3 months respectively. Assessment of socioeconomic status, age, gender, and maternal psychological distress (through the Self Reported Questionnaire (SRQ) were conducted at baseline and follow-up.

Results

We found that psychological distress on SRQ was significantly lower in caregivers of children with intellectual disability in the Titukulane intervention in comparison to the waitlist control group even when the confounding variables of age, gender, and social-economical status were taken into account (Cohen d = 0.08; CI = 0.33-0.754; p =0.0005).

Conclusions

Pyschosocial interventions such as the Titukulane intervention provided over a few months can improve caregiver mental health and quality of life – an important factor for supporting families of children with intellectual disability.
Universal two-dimensional labelled probe-mediated melting curve analysis based on multiplex PCR for rapid typing of plasmodium in a single closed tube
Authors: Xu Haipo , Liu Xiaolong , Liu Jingfeng
Published: April 2022

Nowadays, malaria is still one of the major public health problems which commonly caused by four plasmodium species, especially in the epidemic of COVID-19 harboring similar symptoms of fever or fatigue, which easily result in misdiagnosis. The disadvantages of previous traditional detection methods, such as time-consuming, costly, complicated operation, strong professionalism, indistinguishable typing and so on, lead to the dilemma of difficulty to meet the clinical requirements of rapid, easy and accurate typing of common plasmodiums. Herein, we developed and maximally optimized a universal two-dimensional labelled probe-mediated melting curve analysis (UP-MCA) assay based on multiplex PCR for rapid and accurate typing of five plasmodiums, including novel human plasmodium, Plasmodium knowlesi (Pk), in a single closed tube following genome extraction. The assay showed the limit of detection (LOD) of 10 copies per reaction and can accurately distinguish plasmodium species from intra-plasmodium and other pathogens. In addition, we also proposed and verified different methods of fluorescence-quenching and two dimensional labelled tag for probes that are suitable for UP-MCA assay. Furthermore, its clinical performance was evaluated by 184 samples and showed sensitivity of 100% (164/164) and specificity of 100% (20/20) at 99% confidence interval, respectively, with the microscopy method as gold standard. Taken together, the UP-MCA system showed excellent sensitivity, specificity and accuracy for genotyping of plasmodium, and it meets the requirements of rapidity and convenience for plasmodium detection in clinical routine and has great potential for clinical translation.
Exploring the genetic overlap between 12 psychiatric disorders
Authors: Romero Cato , Werme Josefin , Jansen Philip R. , Gelernter Joel , Stein Murray B. , Levey Daniel , Polimanti Renato ,   VA Million Veteran Program, de Leeuw Christiaan , Posthuma Danielle , Nagel Mats , van der Sluis Sophie
Published: April 2022

The widespread comorbidity among psychiatric disorders (PDs) demonstrated in epidemiological studies1–5 is mirrored by non-zero, positive genetic correlations from large scale genetic studies6–10. We employed several strategies to uncover pleiotropic SNPs, genes and biological pathways7,8 underlying this genetic covariance. First, we conducted cross-trait meta-analysis on 12 PDs to identify pleiotropic SNPs. However, the majority of meta-analytic signal was driven by only one or a few PDs, hampering interpretation and joint biological characterization of the meta-analytic signal. Next, we performed pairwise comparisons of PDs on the SNP, gene, genomic region, gene-set, tissue-type, and cell-type level. Substantial overlap was observed, but mainly among pairs of PDs, and mainly at less stringent p-value thresholds. Only heritability enrichment for “conserved genomic regions” and “nucleotide diversity” was significant for multiple (9 out of 12) PDs. Overall, identification of shared biological mechanisms remains challenging due to variation in power and genetic architecture between PDs.
Clustering ICU patients with sepsis based on the patterns of their circulating biomarkers: a secondary analysis of the CAPTAIN prospective multicenter cohort study
Authors: Misset Benoît , Philippart François , Fitting Catherine , Bedos Jean-Pierre , Diehl Jean-Luc , Hamzaoui Olfa , Annane Djillali , Journois Didier , Parlato Marianna , Moucadel Virginie , Cavaillon Jean-Marc , Coste Joël ,   the Captain Study Group
Published: April 2022

Background

Although sepsis is a life-threatening condition, its heterogeneous presentation likely explains the negative results of most trials on adjunctive therapy. This study in patients with sepsis aimed to identify subgroups with similar immune profiles and their clinical and outcome correlates.

Methods

A secondary analysis used data of a prospective multicenter cohort that included patients with early assessment of sepsis. They were described using Predisposition, Insult, Response, Organ failure sepsis (PIRO) staging system. Thirty-eight circulating biomarkers (27 proteins, 11 mRNAs) were assessed at sepsis diagnosis, and their patterns were determined through principal component analysis (PCA). Hierarchical clustering was used to group the patients and k-means algorithm was applied to assess the internal validity of the clusters.

Results

Two hundred and three patients were assessed, of median age 64.5 [52.0-77.0] years and SAPS2 score 55 [49-61] points. Five main patterns of biomarkers and six clusters of patients (including 42%, 21%, 17%, 9%, 5% and 5% of the patients) were evidenced. Clusters were distinguished according to the certainty of the causal infection, inflammation, use of organ support, pro- and anti-inflammatory activity, and adaptive profile markers.

Conclusions

In this cohort of patients with suspected sepsis, we individualized clusters which may be described with criteria used to stage sepsis. As these clusters are based on the patterns of circulating biomarkers, whether they might help to predict treatment responsiveness should be addressed in further studies.

Trial registration

The CAPTAIN study was registered on clinicaltrials.gov on June 22, 2011, # NCT01378169.
Assessment of magnitude and spectrum of cardiovascular disease admissions and outcomes in Saint Paul Hospital Millennium Medical College, Addis Ababa: A retrospective study
Authors: Mengistu Mekoya D. , Benti Henok
Published: April 2022

Background

Cardiovascular diseases remain the leading cause of death in the world and approximately 80% of all cardiovascular-related deaths occur in low and middle income countries including Ethiopia.

Methods

The aim of the study was to assess the magnitude and spectrum of cardiovascular admissions and its outcomes among medical patients admitted to both Medical Ward and ICU of St. Paul Teaching Hospital from 1st of Jan 2020 to 1st of Jan 2021.

Results

Out of 1,165 annual medical admissions, the prevalence of cardiovascular diseases(CVD) was 30.3%. About 60%(212) of patients had advanced congestive heart failure of diverse causes. Hypertensive heart disease (HHD) was the next predominant diagnosis (41%), and also the leading cause of cardiac diseases followed by rheumatic valvular heart disease(RVHD) (18%) and Ischemic heart disease (IHD) (12.2%), respectively. Yong age, rural residence and female sex were associated with RVHD(p=0.001). Stroke also accounted for 20% of CVD admission (hemorrhagic stroke-17% Vs Ischemic stroke-83%). Hypertension was the predominate risk factor for CVD and present in 46.7%(168) of patients. The mean hospital stay was 12days and in hospital mortality rate was 24.3%, septic shock being the commonest immediate cause of death followed by fatal arrhythmia, brain herniation, and massive PTE.

Conclusion

Cardiovascular diseases were highly prevalent in the study area causing significant morbidity and mortality. Therefore, Comprehensive approach is needed to timely screen for risk reduction, delay or prevent diseases development and subsequent complications.
Attention Samples Items in Visual Working Memory Rhythmically
Authors: Chota Samson , Leto Carlo , van Zantwijk Laura , van der Stigchel Stefan
Published: April 2022

Attention allows us to selectively enhance the processing of specific locations or features in our external environment while simultaneously filtering out momentarily irrelevant information. It is currently hypothesized that this is achieved through the boosting of relevant sensory signals which biases the competition between competing neural representations. Recent neurophysiological and behavioral studies have revealed that attention is a fundamentally rhythmic process, tightly linked to neural oscillations in fronto-parietal networks. Instead of continuously highlighting a single object or location, attention rhythmically alternates between multiple relevant representations at a frequency of 3 – 6 Hz. However attention can not only be directed towards the external world but also towards internal visual working memory (VWM) representations, e.g. when selecting one of several search templates to find corresponding objects in the external world. Two recent studies have revealed that objects in VWM are attended in a similarly rhythmic fashion as perceived objects. We add to the current literature by showing that retro-cues towards multi-feature gratings in VWM initiate a similar theta-rhythmic competition, modulating reaction times in an anti-phasic manner. Our findings add to the converging body of evidence that external and internal visual representations are accessed by highly similar, rhythmic attentional mechanisms.
Genomic analysis of population structure, antimicrobial resistance, and virulent factors of methicillin-resistant Macrococcus caseolyticus in global lineages
Authors: Zhang Yu , Min Shengyi , Sun Yuxuan , Ye Jiaquan , Zhou Zhemin , Li Heng
Published: April 2022

Macrococcus caseolyticus is an opportunistic pathogen frequently detected in dairy products as well as veterinary infections. The present study examined the population structure, antimicrobial resistance, and virulent factors of methicillin-resistant M. caseolyticus isolates in retail meat from Shanghai (n=10) and global isolates from GenBank (n=87). All strains were divided into five lineages that distributed in Europe (82.4%, n = 80), Asia (11.3%, n = 11), North America (4.1%, n = 4), Oceania (1%, n = 1) and Africa (1%, n = 1). MLST typing revealed novel alleles in Chinese M. caseolyticus strains. Furthermore, a total of 24 AMR genes associated with 10 classes of antimicrobial agents were identified in the isolates from global lineages, carried by dominant plasmids such as rep7a, rep22 and repUS56. Comparing to other lineages, genomes from the Chinese lineage carried significantly more AMR genes (p<0.005) and less virulent factors (p<0.001), which may be explained by the local evolution of M. caseolyticus in China. Finally, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were enrolled for morphology comparison between M. caseolyticus and S. aureus, showing that M. caseolyticus has a larger diameter and thicker cell wall. The present study showed geographical variation with regards to MLST profiles, antimicrobial resistance, and virulent factors in global M. caseolyticus lineages. This study suggests that such local evolution of foodborne or livestock origin M. caseolyticus may serve as vehicles for domestic transmission of methicillin resistance in retail meat in China.

Highlights

Global M. caseolyticus strains were divided into five lineages from A to E.

MLST typing revealed novel alleles in Chinese M. caseolyticus strains.

Chinese lineage carried significantly more AMR genes and less virulent factors.

Macrococcus caseolyticus has a larger diameter and thicker cell wall compared with S.aureus.

Macrococcus caseolyticus may enhance the domestic transmission of methicillin resistance in China.
Acute myeloid leukemia expresses a specific group of olfactory receptors
Authors: Guardia Gabriela D. A. , Gonçalves Rafaella N. , Buzzato Vanessa C. , da Costa Juliana B. , Zalcberg Ilana , Ramires Jordana , Malnic Bettina , Gutiyama Luciana M. , Galante Pedro A. F.
Published: April 2022

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. Although new drugs for specific molecular subsets of AML have recently emerged, the 5-year overall survival rate is still approximately 25%. The treatment options for AML have remained stagnant for decades, and novel molecular targets for this disease are needed. Olfactory receptors (ORs) are seven transmembrane G-protein coupled receptors preferentially expressed in sensory neurons, in which they play a critical role in recognizing odorant molecules. Recent studies have revealed ectopic expression and putative function of ORs in nonolfactory tissues and pathologies, including AML. Here, we comprehensively investigated OR expression in 151 AML samples, 51 healthy tissues (approximately 11,200 samples), and 15 other cancer types (6,400 samples). Our analyses identified a group of 19 ORs with a distinct and major expression pattern in AML. The expression of these ORs was experimentally validated in an independent set of AML samples and cell lines. We also identified an OR signature with prognostic value for AML patients. Finally, we identified cancer-related genes that were coexpressed with the ORs in the AML samples. In summary, we conducted a high-throughput computational study to identify ORs that can be used as novel biomarkers for the diagnosis of AML and as potential drug targets. The same approach may be used to investigate OR expression in other types of cancer.
The effect of biohanin A isolated from the callus culture of meadow clover (Trifolium pratense L.) on the life expectancy and survival of Caenorhabditis elegans
Authors: Milentyeva Irina Sergeevna , Drozdova Margarita Yuryevna , Le Violeta Mironovna
Published: April 2022

Oxidative stress, in which healthy aging is limited, is a problem, since in the process there is an uncontrolled production of reactive radicals that negatively affect cells. Heat stress is closely related to oxidative stress, as it stimulates the production of radicals. Meadow clover (Trifolium pratense L.) is a promising source of isoflavonoids that have various positive effects on the body. The aim of the work is to study the effect of biohanin A, isolated from Trifolium pratense L. callus cultures, on the life expectancy of the C. elegans model organism, as well as its survival under oxidative and thermal stress.

It was found that biohanin A increased the lifespan of C. elegans worms. The best concentration was determined - 100 microns, at which the survival rate of nematodes after 61 days of incubation was 16.0%. After 48 hours, the survival rate of worms was the highest (87.1%) at a concentration of biohanin A of 200 microns. Other concentrations 10, 50, 100 (81,2, 83,0, 82,4 %) they also showed a higher survival rate compared to the control (74.0%). In addition, the survival rate under heat stress of C. elegans was higher by 12.0; 8.4; 4.0% compared with the control. Thus, the results show the antioxidant potential of biohanin A from plant material under oxidative and thermal stress. The substance also had a positive effect on the lifespan of C. elegans.
Pre-procedural testing improves estimated COVID-19 prevalence and trends
Authors: Pang Genevieve C. , Hou Amy T. , Bayudan Krizhna L. , Frank Ethan A. , Pastiglione Jennifer , Pang Lorrin W.
Published: April 2022

Background

COVID-19 positivity rates reported to the public may provide a distorted view of community trends because they tend to be inflated by high-risk groups, such as symptomatic patients and individuals with known exposures to COVID-19. This positive bias within high-risk groups has also varied over time, depending on testing capability and indications for being tested. In contrast, throughout the pandemic, routine COVID-19 screening tests for elective procedures and operations unrelated to COVID-19 risk have been administered by medical facilities to reduce transmission to medical staffing and other patients. We propose the use of these pre-procedural COVID-19 patient datasets to reduce biases in community trends and better understand local prevalence.

Methods

Using patient data from the Maui Medical Group clinic, we analyzed 12,640 COVID-19 test results from May 1, 2020 to March 16, 2021, divided into two time periods corresponding with Maui’s outbreak.

Results

Mean positivity rates were 0.1% for the pre-procedural group, 3.9% for the symptomatic group, 4.2% for the exposed group, and 2.0% for the total study population. Post-outbreak, the mean positivity rate of the pre-procedural group was significantly lower than the aggregate group (all other clinic groups combined). The positivity rates of both pre-procedural and aggregate groups increased over the study period, although the pre-procedural group showed a smaller rise in rate.

Conclusions

Pre-procedural groups may produce different trends compared to high-risk groups and are sufficiently robust to detect small changes in positivity rates. Considered in conjunction with high-risk groups, pre-procedural marker groups used to monitor understudied, low-risk subsets of a community may improve our understanding of community COVID-19 prevalence and trends.
Understanding and comparing the globe-trotting cancer patient with the locally managed patient: A case control study
Authors: Wangai Mary W , Wangai Frederick K , Njiiri Francis , Kinuthia John , Wangai Enan N. , Nyongesa Catherine , Wangai Paul
Published: April 2022

Medical tourism is characterized by people seeking treatment abroad for various medical conditions due to varied reasons, many of whom benefit from specialized care for non-communicable diseases. Conversely, there are associated negative effects such as medical complications and weakened health systems. Currently, there is paucity of scientific evidence on factors influencing seeking treatment benefits abroad. This study sought to compare patient-related factors associated with choice of cancer treatment center locally or abroad, to understand reasons for seeking treatment outside Kenya.

Materials and Methods

As a case-control study, 254 cancer patients were randomly sampled to compare responses from those who chose to receive treatment abroad or in Kenya. The cases were recruited from Ministry of Health while the controls from Kenyatta National Hospital and Texas Cancer Center. Data was analyzed using SPSS Software Version 21. Descriptive statistics, bivariate and multiple logistic regression analysis was carried out. Level of significance was set at 5%.

Results

Out of 254 respondents, 174 (69.5%) were treated for cancer in Kenya and 80 (31.5%) in India. We found that cost effectiveness was a significant factor for over 73% of all respondents. The study revealed independent predictors for seeking treatment in India were: monthly income higher than US$ 250; every additional month from diagnosis increased likelihood by 1.16 times; physician advice (Odds Ratio(OR) 66; 95% Confidence Interval(CI) 7.9 −552.9); friends and family (OR 42; 95% CI 7.07-248.6); and perception of better quality of care (OR 22.5; 95% CI 2.2-230.6).

Conclusion

Reasons patients with cancer sought treatment in India are multifactorial. Several of these can be addressed to reverse out-ward bound medical tourism and position Kenya to be a regional hub as per the country’s development blueprint. It will require strengthening the health system accordingly and sensitizing the medical fraternity and general public on the same.
The UT Health Psychological Autopsy Interview Schedule (UTH- PAIS) – Description and Reliability of Diagnoses and Transdiagnostic Personality Measures
Authors: Meyer Thomas D. , Godfrey Christopher J. , Walss-Bass Consuelo
Published: April 2022

Few studies have used psychological autopsies to evaluate large and diverse populations on transdiagnostically relevant variables such as personality, temperament, and trauma exposure, rather they tend to focus on specific psychiatric disorders or manner of death. We therefore developed the UT Health Psychological Autopsy Interview Schedule (UTH-PAIS). The measure is described, and our results show that that the PAIS diagnoses and dimensions can be reliably assessed. Furthermore, we were able to show that our sample of donated brains overall matches the demographic characteristics of larger pool of individuals receiving a medical autopsy. In the Discussion we review the strengths and potential limitations of the study and outline in which context the PAIS will prove to be useful.
Impairment and characteristics of postural control sub-components in people with COPD: a scoping review
Authors: Pichon Romain , Van Hove Olivier , Ménard Mathieu , Hearing Diane , Crétual Armel
Published: April 2022

Purpose

Impairment of postural control is a common extra-respiratory manifestation in people with COPD. However, the precise characteristics of this alteration are not clearly known. The “Systems Framework for Postural Control” which define postural control sub-components, is a relevant tool to explore this field. The main aim of this review was to identify which postural control sub-components are impaired in patients with COPD and to summarize characteristics for each sub-component. A secondary aim was to precise the relation between postural control and activities of daily living.

Materials and methods

A scoping review was conducted, according to the JBI methodology. Pubmed, Cochrane Library, Scielo, Google Scholar, Open Grey and HAL were searched from inception to March 2021. The search was performed in English and French.

Results

Seventy-seven articles were included. There was evidence of a potential impairment for most of the postural control sub-components. Characteristics of every sub-component alteration were heterogeneous. Even if the relation was poorly studied, reduced postural control seemed to be associate with difficulties in activities of daily living.

Conclusion

Patients with COPD could experiment impairment among a wide range of postural control sub-components. Future research must clarify if a common pattern of modification exits for this alteration.

Implications for rehabilitation

Impairment of postural control is a common extra-respiratory manifestation in patients with COPD and so clinicians must include it in their clinical reasoning

Numerous postural control sub-components could be altered in patients with COPD, suggesting that postural control assessment must be holistic.

This scoping review shows that characteristics of postural control impairment are varied and that there may be no common pattern at the COPD population level.
Association between metabolic syndrome and humoral immune response to Pfizer–BioNTech vaccine in healthcare workers
Authors: Hoang Dong Van , Yamamoto Shohei , Fukunaga Ami , Inoue Yosuke , Mizoue Tetsuya , Ohmagari Norio
Published: April 2022

Purpose

The clustering of metabolic abnormalities may weaken vaccine-induced immunity, but epidemiological data regarding SARS-CoV-2 vaccines are scarce. The present study examined the cross-sectional association between metabolic syndrome (MetS) and humoral immune response to Pfizer–BioNTech vaccine among healthcare workers.

Methods

Participants were 946 healthcare workers, aged 21–75 years, who had completed the second dose of Pfizer–BioNTech vaccine 1–3 months before the survey. MetS was defined according to the Joint Interim Statement. SARS-CoV-2 spike immunoglobulin G (IgG) antibody was measured using quantitative assays. Multivariable linear regression was used to estimate the geometric mean titers (GMT) and geometric mean ratio (GMR) of IgG titers, relative to MetS status.

Results

A total of 51 participants (5.4%) had MetS. Healthcare workers with MetS had a significantly lower IgG titer (GMT 3882; 95% confidence interval [CI], 3124–4824) than those without MetS (GMT 5033; 95% CI, 4395–5764); the GMR was 0.77 (95% CI 0.64–0.93). The GMR for IgG titers among those having 0 (reference group), 1, 2, 3, or ≥ 4 MetS components was 1.00, 1.00, 0.89, 0.86 and 0.61, respectively (Ptrend = 0.004).

Conclusion

Results suggest that having MetS and a greater number of its components are associated with a weaker humoral immune response to the Pfizer–BioNTech vaccine.
Rapid displacement of SARS-CoV-2 variants within Japan correlates with cycle threshold values on routine RT-PCR testing
Authors: Wright Danelle , Chan Carmen , Chaochaisit Wirawit , Ogawa Mio , Tanaka Junko , Nozaki Satoshi , Narita Shinji , Shimizu Eisuke , Aoshima Hideyuki , Baran Iri Sato
Published: April 2022

Background

The rapid spread of SARS-CoV-2 worldwide has led to the emergence of new variants due to the presence of mutations that alter viral characteristics, but there have been few studies on trends in viral lineages in Japan, an island country. We hypothesized that changes in cycle threshold (Ct) values on reverse transcription polymerase chain reaction (RT-PCR) reflect the prevalent variants during a given period.

Methods

We performed next-generation sequencing of positive samples to identify the viral lineages in Japan in 2021 and compared variant prevalence with the average Ct values on routine RT-PCR using 4 primer sets.

Results

Based on 3 sequencing runs, the highly transmissible Alpha variant, which prevailed over other lineages, such as R.1, from April 2021, was dominated by the even stronger Delta variant between July and August 2021 in Japan. The decrease in our routine RT-PCR Ct values with 4 primer sets correlated with these fluctuations in lineage prevalence over time.

Conclusions

We confirmed that our RT-PCR protocol reflects the trends in SARS-CoV-2 variant prevalence over time regardless of sequence mutation. This may aid in the tracking of new variants in the population.
Comparison of the accuracy of 9 intraocular lens power calculation formulas using partial coherence interferometry
Authors: Maroun Anthony , El Shami Mohamad , Hoyek Sandra , Antoun Joelle
Published: April 2022

Purpose

To compare the accuracy of 9 intraocular lens (IOL) power calculation formulas (SRK/T, Hoffer Q, Holladay 1, Haigis, Barrett Universal II, Kane, EVO 2.0, Ladas Super formula and Hill-RBF 3.0) using partial coherence interferometry (PCI).

Methods

Data from patients having uncomplicated cataract surgery with the insertion of 1 of 3 IOL types were included. All preoperative biometric measurements were performed using PCI. Prediction errors (PE) were deduced from refractive outcomes evaluated 3 months after surgery. The mean prediction error (ME), mean absolute prediction error (MAE), median absolute prediction error (MedAE), and standard deviation of prediction error (SD) were calculated, as well as the percentage of eyes with a PE within ±0.25, ±0.50, ±0.75 and ±1.00D for each formula.

Results

Included in the study were 126 eyes of 126 patients. Kane achieved the lowest MAE and SD across the entire sample as well as the highest percentage of PE within ±0.50D, and was proven to be more accurate than Haigis and Hoffer Q (P <.001). For an axial length of more than 26.0 mm, EVO 2.0 and Barrett obtained the lowest MAEs, with EVO 2.0 and Kane showing a higher percentage of prediction at ±0.50D compared to old generation formulas except for SRK/T (P =.04).

Conclusion

All investigated formulas achieved good results; there was a tendency towards better outcomes with new generation formulas, especially in atypical eyes.
Theoretical derivation and clinical validation of the resolution limit of human eye to spherical lens change:A Self-controlled Study
Authors: Yi Zhen , Jie Gao , Kai Cao , Jing Shen , wei Zhang , Yun Dai
Published: April 2022

Background/Aims

To deduce theoretically and verify the resolution limit of human eye to spherical lens change for more reasonable design of the trial lenses.

Methods

First, the resolution limit of discernible change in spherical power was derived based on the optical model. Then, the volunteers were observed to see if they could perceive the changes in spherical power as per the resolution limit and compare the difference in the best corrected visual acuity obtained with the resolution limit and interval of 0.25D.

Results

Assuming that the cone cell diameter is 3 μm and the pupil diameter of 4 mm, the theoretically resolution limit was 0.05D. When the diopter of spherical power was increased, the ratios of ability to perceive 0.05D spherical lens change were 98.3% and 96.7% in right and left eyes. When the diopter of spherical power was decreased, the ratios of ability to perceive 0.05D spherical lens change were 78.9% and 83.2% in right and left eyes. The best corrected visual acuity obtained with the 0.05 D interval trial lens was significantly better than in the 0.25 D interval on both eyes (Right eye -0.04±0.07 vs -0.02±0.06, t=6.729, P<0.001; Left eye -0.07±0.06 vs -0.04±0.06, t=8.825, P<0.001).

Conclusion

The resolution limit of human eye to spherical lens change was about 0.05D and the better corrected visual acuity can be obtained by adjusting the spherical power at an interval of 0.05D.

What is already known on this topic

At present, the spherical power is generally adjusted at 0.25D for optometry. In clinical practice, we find that a more than 80% of myopia patients with clear red prototypes will directly see clear green in case of a decrease by 0.25D, unable to achieve the red-green balance.

What this study adds

More than 80% of myopia patients can perceive the changes in spherical power as per 0.05D.

How this study might affect research, practice or policy

Adjusting the spherical power per 0.05 D can help us to achieve a higher full correction rate (>80%) and realize better visual acuity.

[Synopsis/Precis]

The resolution limit of human eye to spherical lens change is about 0.05D and better corrected visual acuity can be obtained by adjusting the spherical power at an interval of 0.05D than 0.25D.
Generation and characterization of iPSC lines (UOHi001-A, UOHi002-A) From a patient with SHANK3 mutation and her healthy mother
Authors: Nayak Ritu , Rosh Idan , Rabinski Tatiana , Percia Menachem Mendel , Stern Shani
Published: April 2022

Phelan-McDermid syndrome (PMS) is a rare genetic condition that causes global developmental disability, delayed or absent speech, and autism spectrum disorder. The loss of function of one copy of SHANK3, which codes for a scaffolding protein found in the postsynaptic density of synapses, has been identified as the main cause of PMS. We report the generation and characterization of two induced pluripotent stem cell (iPSC) lines derived from one patient with a SHANK3 mutation and the patient’s mother as a control. Both lines expressed pluripotency markers, differentiated into the three germ layers, retained the disease-causing mutation, and displayed normal karyotypes.
Sun4 is a type II transmembrane protein of the spermatid inner nuclear membrane that forms heteromeric assemblies with Sun3 and interacts with Lamin B3
Authors: Thoma Hanna , Grünewald Luisa , Pasch Elisabeth , Alsheimer Manfred
Published: April 2022

SUN domain proteins are conserved proteins of the nuclear envelope and key components of the LINC complexes (linkers of the nucleoskeleton and the cytoskeleton). Previous studies have demonstrated that the testis-specific SUN domain protein Sun4 is a vital player in spermatogenesis, critically involved in the directed shaping of the spermatid nucleus. Its molecular properties relating to this crucial function, however, have remained largely unknown. Previous studies presented quite controversial data for the general organization and orientation of Sun4 within the spermatid nuclear envelope. In the present study, we have re-evaluated this issue in detail and present new robust data on the Sun4 topology and its interactions at the nucleo-cytoplasmic junction. We identified Sun4 as an integral protein of the inner nuclear membrane, sharing a classical SUN domain protein topology. Similar to other SUN domain proteins, the C-terminal SUN domain of Sun4 locates to the perinuclear space and the N-terminus is directed to the nucleoplasm, where it interacts with the spermiogenesis specific Lamin B3. We found that Sun4 in its natural environment forms heteromeric assemblies with Sun3 and, beyond this, it is crucially involved in the regulation of Sun3 expression. Together, our results contribute to a better understanding of the specific function of Sun4 at the spermatid nucleo-cytoplasmic junction and the entire process of sperm-head formation.

Summary statement

In our current study, we have analyzed in detail the biochemical and dynamic properties of the testis-specific SUN domain protein Sun4 and we provide novel insights into its interaction behavior at the spermatid nucleo-cytoplasmic junction.
Landscape structure is a key driver of protist diversity along elevation gradients in the Swiss Alps
Authors: Seppey Christophe V.W. , Lara Enrique , Broennimann Olivier , Guisan Antoine , Malard Lucie , Singer David , Yashiro Erika , Fournier Bertrand
Published: April 2022

Context

Human-induced changes in landscape structure are among the main causes of biodiversity loss. Despite their important contribution to biodiversity and ecosystem functioning, microbes - and particularly protists - remain spatially understudied. Soil microbiota are most often driven by local soil properties, but the influence of the surrounding landscape is rarely assessed.

Objectives

We assessed the effect of landscape structure on soil protist alpha and beta diversity in meadows in the western Swiss Alps.

Methods

We sampled 178 plots along an elevation gradient representing a broad range of environmental conditions and land-use. We measured landscape structure around each plot at 5 successive spatial scales (i.e. neighbourhood windows of increasing radius, ranging from 100 to 2000 m around a plot). We investigated the changes of protist alpha and beta diversity as a function of landscape structure, local environmental conditions and geographic distance.

Results

Landscape structures played a key role for protist alpha and beta diversity. The percentage of meadows, forests, or open habitats had the highest influence among all landscape metrics. The importance of landscape structure was comparable to that of environmental conditions and spatial variables, and increased with the size of the neighbourhood window considered.

Conclusions

Our results suggest that dispersal from neighbouring habitats is a key driver of protist alpha and beta diversity which highlight the importance of landscape-scale assembly mechanisms for microbial diversity. Landscape structure emerges as a key driver of microbial communities which has profound implications for our understanding of the consequences of land-use change on soil microbial communities and their associated functions.
Efficient and sensitive profiling of RNA-protein interactions using TLC-CLIP
Authors: Ernst Christina , Duc Julien , Trono Didier
Published: April 2022

RNA-binding proteins are instrumental for post-transcriptional gene regulation, yet transcriptomewide methods to profile RNA-protein interactions remain technically challenging. We present an improved library preparation strategy for crosslinking and immunoprecipitation (CLIP) that involves tailing and ligation of cDNA molecules (TLC) for increased sensitivity and efficiency. TLC-CLIP eliminates time-consumingpurifications, reduces sample loss and minimises experimental steps, allowing precise profiling of RNA-protein interactions from limited starting material at nucleotide resolution.
Comprehensive validation of fasting- and oral glucose tolerance test-based indices of insulin secretion against gold-standard measures
Authors: Prystupa Katsiaryna , Renklint Rebecka , Chninou Youssef , Otten Julia , Fritsche Louise , Hörber Sebastian , Peter Andreas , Birkenfeld Andreas , Fritsche Andreas , Heni Martin , Wagner Robert
Published: April 2022

Background and aims

With prediabetes and diabetes increasingly recognized as heterogenous conditions, assessment of beta-cell function is gaining clinical importance to identify disease subphenotypes. Our study aims to comprehensively validate all types of surrogate indices based on OGTT- and fasting-measurements in comparison with gold standard methods.

Materials and methods

The hyperglycaemic clamp extended with GLP-1 infusion and IVGTT, as well as OGTT, was performed in two well-phenotyped cohorts. The gold-standard-derived indices were compared with surrogate insulin secretion markers, derived from fasting state and OGTT, using both Pearson’s and Spearman’s correlation coefficients. The insulin- and C-peptide-based indices were analysed separately in different groups of glucose tolerance and the entire cohorts.

Results

The highest correlation coefficients were found for AUC (I0-30)/AUC (G0-30), first-phase Stumvoll and Kadowaki model. These indices have high correlation coefficients with measures obtained from both insulin and C-peptide levels from IVGTT and hyperglycaemic clamp. AUC (I0-30)/AUC (G0-30), first-phase Stumvoll, AUC (I0-120)/AUC (G0-120) and BIGTT-AIR0-60-120 demonstrated the strongest association with incretin-stimulated insulin response.

Conclusion

We have identified glucose- and GLP-1-stimulated insulin secretion indices, derived from OGTT and fasting state, that have the strongest correlation with gold-standard measures and could be potentially used in future researches and clinical practice.
Chromatin remodeler developmental pluripotency associated factor 4 (DPPA4) is a candidate gene for alcohol-induced developmental disorders
Authors: Auvinen P , Vehviläinen J , Marjonen H , Modhukur V , Sokka J , Wallén E , Rämö K , Ahola L , Salumets A , Otonkoski T , Skottman H , Ollikainen M , Trokovic R , Kahila H , Kaminen-Ahola N
Published: April 2022

Alcohol affects embryonic development, causing a variable fetal alcohol spectrum disorder (FASD) phenotype with neuronal disorders and birth defects. To explore the etiology of FASD, we collected an exceptional cohort of 80 severely alcohol-exposed and 100 control newborns and performed genome-wide DNA methylation and gene expression analyses of placentas. DPPA4, FOXP2, and TACR3 with significantly decreased DNA methylation were discovered – particularly the regulatory region of DPPA4 in the early alcohol-exposed placentas. When human embryonic stem cells (hESCs) were exposed to alcohol in vitro, significantly altered regulation of DPPA2, a closely linked heterodimer of DPPA4, was observed. While the regulatory region of DPPA4 was unmethylated in both control and alcohol-exposed hESCs, alcohol-induced decreased DNA methylation similar to placenta was seen in in vitro differentiated mesodermal and ectodermal cells. Furthermore, common genes with alcohol-associated DNA methylation changes in placenta and hESCs were linked exclusively to the neurodevelopmental pathways, which emphasizes the value of placental tissue when analyzing the effects of prenatal environment on human development. Our study shows the effects of early alcohol exposure on human embryonic and extraembryonic cells, introduces candidate genes for alcohol-induced developmental disorders, and reveals potential biomarkers for prenatal alcohol exposure.
To mask, or not to mask, Alice and Bob’s dating dilemma
Authors: (Sam) Ma Zhanshan , Zhang Ya-Ping
Published: April 2022

Abstract

Face masking in current COVID-19 pandemic seems to be a deceivingly simple decision-making problem due to its multifaceted nature. Questions arising from masking span biomedicine, epidemiology, physics, and human behaviors. While science has shown masks work generally, human behaviors (particularly under influences of politics) complicate the problem significantly given science generally assumes rationality and our minds are not always rational and/or honest. Minding minds, a legitimate concern, can also make masking legitimately confusing. To disentangle the potential confusions, particularly, the ramifications of irrationality and dishonesty, here we resort to evolutionary game theory. Specifically, we formulate and analyze the masking problem with a fictitious pair of young lovers, Alice and Bob, as a Sir Philip Sydney (SPS) evolutionary game, inspired by the handicap principle in evolutionary biology and cryptography figures in computer science. With the proposed ABD (Alice and Bob’s dating dilemma) as an asymmetric four-by-four strategic-form game, 16 strategic interactions were identified, and six of which may reach equilibriums with different characteristics such as separating, pooling, and polymorphic hybrid, being Nash, evolutionarily stable or neutrally stable. The six equilibrium types seem to mirror the diverse behaviors of mask believers, skeptics, converted, universal masking, voluntarily masking, coexisted and/or divided world of believers and skeptics. We suggest that the apparently simple ABD game is sufficiently general not only for studying masking policies for populations (viareplicator dynamics), but also for investigating other complex decision-making problems with COVID-19 pandemic including lockdownvs. reopening, herd immunityvs. quarantines, and aggressive tracingvs. privacy protection.
Coupling and Heterogeneity Modulate Pacemaking Capability in Healthy and Diseased Two-Dimensional Sinoatrial Node Tissue Models
Authors: Campana Chiara , Ricci Eugenio , Bartolucci Chiara , Severi Stefano , Sobie Eric A.
Published: April 2022

Both experimental and modeling studies have attempted to determine mechanisms by which a small anatomical region, such as the sinoatrial node (SAN), can robustly drive electrical conduction in the human heart. However, despite important advances from prior research, important questions remain unanswered. This study aimed to investigate, through mathematical modeling, the role of intercellular coupling and cellular heterogeneity in synchronization and pacemaking within the healthy and diseased SAN. In a multicellular computational model of a monolayer of either human or rabbit SAN cells, simulations revealed that heterogenous cells synchronize their discharge frequency into a unique beating rhythm across a wide range of cellular heterogeneity and intercellular coupling. However, an insightful and unanticipated behavior appears in pathological conditions precipitated by perturbations of certain ionic currents (gCaL= 0.5): an intermediate range of intercellular coupling (900-4000 MΩ) is beneficial to the human SAN automaticity, enabling a very small portion of tissue (3.4%) to drive propagation, which fails with both lower and higher resistances. This protective effect of intercellular coupling and heterogeneity, seen in both human and rabbit tissues, highlights the remarkable resilience of the SAN. Overall, the model here developed allowed insight into the mechanisms of automaticity of the human sinoatrial node. The simulations suggest that certain degrees of gap junctional expressions protect the SAN from ionic perturbations that might be caused by drugs or mutations.
Context-dependent choice and evaluation in real-world consumer behavior
Authors: Otto A. Ross , Devine Sean , Schulz Eric , Bornstein Aaron M. , Louie Kenway
Published: April 2022

A body of work spanning neuroscience, economics, and psychology indicates that decisionmaking is context-dependent, which means that the value of an option depends not only on the option in question, but also on the other options in the choice set—or the ‘context’. While context effects have been observed primarily in small-scale laboratory studies with tightly constrained, artificially constructed choice sets, it remains to be determined whether these context effects take hold in real-world choice problems, where choice sets are large and decisions driven by rich histories of direct experience. Here, we investigate whether valuations are context-dependent in real-world choice by analyzing a large restaurant rating dataset (Yelp.com) as well as two independent replication datasets which provide complementary operationalizations of restaurant choice. We find that users make fewer ratings-maximizing choices in choice sets with higher-rated options—a hallmark of context-dependent choice— and that post-choice restaurant ratings also varied systematically with the ratings of unchosen restaurants. Furthermore, in a follow-up laboratory experiment using hypothetical choice sets matched to the real-world data, we find further support for the idea that subjective valuations of restaurants are scaled in accordance with the choice context, providing corroborating evidence for a general mechanistic-level account of these effects. Taken together, our results provide a potent demonstration of context-dependent choice in real-world choice settings, manifesting both in decisions and subjective valuation of options.