bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of non-invasive brain stimulation (NIBS) on vestibulopathy disorders
Authors: Fonseca Bruno Henrique de Souza , de Andrade Pedro Henrique Sousa , Borges Otávio , Mariana de Aquino Miranda Jessica , Bazan Rodrigo , de Souza Luciane Aparecida Pascucci Sande , José Luvizutto Gustavo
Published: April 2022

Objectives

New types of treatments have emerged, such as non-invasive brain stimulation (NIBS), to treat chronic vestibular dysfunction (VD). Considering that NIBS is a promising approach to reduce VD symptoms, this review was aimed to analyze the effects of NIBS in patients with VD.

Methods

We adhered to the methods described in the Cochrane Handbook for Intervention Reviews. The eligibility criteria were as follows: (a) individuals with vestibulopathy having clinical and neuroimaging; (b) Interventions: non-invasive brain stimulation, this intervention comprised transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS); (c) Control: any comparison or sham; and (d) Outcomes: dizziness and balance. We included randomized controlled trials and non-randomized studies from July 2004 to February 2020. We searched the PubMed, CINAHL, Web of Science, Scopus, Cochrane, and Ovid databases. Two pairs of reviewers independently screened all titles and abstracts. Two authors assessed the risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the certainty of the evidence for each outcome.

Results

We identified 136 studies, and included two studies. Both studies used tDCS application. One study used anodal cerebellar tDCS or sham at 2 mA for 25 min associated with vestibular rehabilitation therapy (VRT), and the other study used anodal tDCS over the left dorsolateral prefrontal cortex (F3) for 25–30 min associated with VRT at home. Both studies showed clinical improvement in the Dizziness Handicap Inventory (DHI), State-Trait Anxiety Inventory (STAI), Activities-Specific Balance Confidence (ABC), and Self-Rating Depression Scale (SDS) scores. Both studies presented higher-quality evidence on the GRADE scale and a low risk of bias.

Conclusions

Based on two studies, anodal tDCS over F3 or the cerebellum associated with VRT improved chronic vestibular symptoms.
Probability density functions of quantum mechanical observable uncertainties
Authors: Zhang Lin , Huang Jinping , Wang Jiamei , Fei Shao-Ming
Published: April 2022

We study the uncertainties of quantum mechanical observables, quantified by the standard deviation (square root of variance) in Haar-distributed random pure states. We derive analytically the probability density functions (PDFs) of the uncertainties of arbitrary qubit observables. Based on these PDFs, the uncertainty regions of the observables are characterized by the support of the PDFs. The state-independent uncertainty relations are then transformed into the optimization problems over uncertainty regions, which opens a new vista for studying state-independent uncertainty relations. Our results may be generalized to multiple observable cases in higher dimensional spaces.
Open charm mesons and charmonia in magnetized strange hadronic matter *
Authors: C. S. Amal Jahan , Mishra Amruta
Published: April 2022

We investigate the in-medium masses of open charm mesons (D(

,

),

(

,

),

(

,

)) and charmonium states (

,

,

,

,

) in strongly magnetized isospin asymmetric strange hadronic matter using a chiral effective model. In the presence of a magnetic field, the number and scalar densities of charged baryons have contributions from Landau energy levels. The mass modifications of open charm mesons result from their interactions with nucleons, hyperons, and the scalar fields (the non-strange field σ, strange field ζ, and isovector field δ) in the presence of a magnetic field. The mass modifications of the charmonium states result from the modification of gluon condensates in a medium simulated by the variation in the dilaton field (χ) in the chiral effective model. The effects of finite quark masses are also incorporated in the trace of the energy-momentum tensor in quantum chromodynamics to investigate the mass shifts of charmonium states. The in-medium masses of open charm mesons and charmonia are observed to decrease with an increase in baryon density. The charged

,

,

, and

mesons have additional positive mass shifts due to Landau quantization in the presence of a magnetic field. The effects of the strangeness fraction are observed to be more dominant for

mesons compared with D mesons. The mass shifts of charmonia are observed to be larger in hyperonic media compared with nuclear media when the effect of the finite quark mass term is neglected. These medium mass modifications can have observable consequences on the production of the open charm mesons and charmonia in high-energy asymmetric heavy-ion collision experiments.
Spike sorting: new trends and challenges of the era of high-density probes
Authors: Buccino Alessio P , Garcia Samuel , Yger Pierre
Published: April 2022

Recording from a large neuronal population of neurons is a crucial challenge to unravel how information is processed by the brain. In this review, we highlight the recent advances made in the field of ‘spike sorting’, which is arguably a very essential processing step to extract neuronal activity from extracellular recordings. More specifically, we target the challenges faced by newly manufactured high-density multi-electrode array devices (HD-MEA), e.g. Neuropixels probes. Among them, we cover in depth the prominent problem of drifts (movements of the neurons with respect to the recording devices) and the current solutions to circumscribe it. In addition, we also review recent contributions making use of deep learning approaches for spike sorting, highlighting their advantages and disadvantages. Next, we highlight efforts and advances in unifying, validating, and benchmarking spike sorting tools. Finally, we discuss the spike sorting field in terms of its open and unsolved challenges, specifically regarding scalability and reproducibility. We conclude by providing our personal view on the future of spike sorting, calling for a community-based development and validation of spike sorting algorithms and fully automated, cloud-based spike sorting solutions for the neuroscience community.
Bio-inspired navigation and exploration system for a hexapod robotic platform
Authors: Pardo-Cabrera Josh , Rivero-Ortega Jesús D , Hurtado-López Julián , Ramírez-Moreno David F
Published: April 2022

This paper presents a biologically inspired system for guiding and controlling a virtual hexapod robot. Our navigation and exploration system is composed of subsystems that execute processes of path integration, action selection, actuator control and correction of the robot’s orientation. For the subsystem that serves the path integration function we modified an existing model of bio-inspired vector summation by adding the capability of performing online calculation. For the action selection subsystem that allows to switch between the behaviors of exploration, approaching a target and homing we modified an existing model of decision making for mediating social behaviors in mice. We added an additional circuit that projects a signal to the units representing each of the behaviors. In the case of the actuator control subsystem, the structure of a central pattern generator model that incorporates feedback and adaptation was used as the base for generating and transforming signals for the actuators. Finally, the orientation correction subsystem is a novel model that determines an error value from a desired and the current orientations. The proposed models were simulated as independent scripts and then implemented as ROS (Robot Operating System) nodes for controlling a robot simulation in Gazebo.
Scaling of voltage controlled magnetic anisotropy based skyrmion memory and its neuromorphic application
Authors: Akanda Md Rakibul Karim
Published: April 2022

Voltage controlled skyrmion memory requires less energy compared to current controlled method where voltage changes magnetic anisotropy (VCMA) and Dzyaloshinskii-Moriya interaction (DMI). Ferromagnetic (FM) and synthetic antiferromagnetic (SAFM) memory devices are simulated using electric field control method where gate and gap width are chosen as smaller than skyrmion size so that skyrmion can feel the change in voltage polarity in the neighbouring gate and moves accordingly. Scaling of memory device is performed which shows SAFM memory can be made much narrower compared to FM memory as skyrmion diameter also depends on width of the structure. Effects of device structure and skyrmion-skyrmion repulsion force on skyrmion diameter variation are shown in cylindrical structure considering effect of demagnetizing field. Apart from these, neuromorphic application is considered where skyrmion moves from central square neuron region to surrounding synapse region or vice versa by the application of voltage. Switching time, voltage range, energy and scaling of device dimensions are shown for synapse-neuron having different number of skyrmions where multiple skyrmions represent different weight in the neuromorphic circuit.
A model to determine soiling, shading and thermal losses from PV yield data
Authors: Ghosh S , Roy J N , Chakraborty C
Published: April 2022

Apart from being a clean source of energy, photovoltaic (PV) power plants are also a source of income generation for its investors and lenders. Therefore, mitigation of system losses is crucial for economic operation of PV plants. Combined losses due to soiling, shading and temperature in PV plants go as high as 50%. Much of these losses are unaccounted initially, which can jeopardize the economic viability of PV projects. This paper aims to provide a model to determine losses due to soiling, shading and temperature using quantities like irradiance, cell temperature, DC power and current, which are readily available in PV yield data captured by the remote monitoring system, without involving any additional sensors or equipment. In this study, soiling, shading and thermal losses were calculated using PV yield data obtained from a 30-kWp PV plant located in Kharagpur, India. The results showed soiling and shading losses as high as 25.7% and 9.7%, respectively, in the month of December. Soiling loss was verified by measuring transmittance loss of coupon glasses installed in the vicinity of the plant. Shading loss was verified by shadow simulation using an architectural tool (SketchUp). Array thermal loss obtained using the proposed methodology was found to be in line with the estimated value obtained from PVsyst simulation. Additionally, using time-series data, the energy losses corresponding to soiling, shading and temperature effects were calculated by a numerical-integration technique. The monetary loss due to these energy losses thus obtained provides criteria for deciding when to mitigate the sources of these losses.
Hidden in plain sight: challenges in proteomics detection of small ORF-encoded polypeptides
Authors: Fijalkowski Igor , Willems Patrick , Jonckheere Veronique , Simoens Laure , Van Damme Petra
Published: April 2022

Genomic studies of bacteria have long pointed toward widespread prevalence of small open reading frames (sORFs) encoding for short proteins, <100 amino acids in length. Despite the mounting genomic evidence of their robust expression, relatively little progress has been made in their mass spectrometry-based detection and various blanket statements have been used to explain this observed discrepancy. In this study, we provide a large-scale riboproteogenomics investigation of the challenging nature of proteomic detection of such small proteins as informed by conditional translation data. A panel of physiochemical properties alongside recently developed mass spectrometry detectability metrics was interrogated to provide a comprehensive evidence-based assessment of sORF-encoded polypeptide (SEP) detectability. Moreover, a large-scale proteomics and translatomics compendium of proteins produced by Salmonella Typhimurium (S. Typhimurium), a model human pathogen, across a panel of growth conditions is presented and used in support of our in silico SEP detectability analysis. This integrative approach is used to provide a data-driven census of small proteins expressed by S. Typhimurium across growth phases and infection-relevant conditions. Taken together, our study pinpoints current limitations in proteomics-based detection of novel small proteins currently missing from bacterial genome annotations.
The dynamic effect of genetic variation on the in vivo ER stress transcriptional response in different tissues
Authors: Russell Nikki D , Chow Clement Y
Published: April 2022

The genetic regulation of gene expression varies greatly across tissue-type and individuals and can be strongly influenced by the environment. Many variants, under healthy control conditions, may be silent or even have the opposite effect under diseased stress conditions. This study uses an in vivo mouse model to investigate how the effect of genetic variation changes with cellular stress across different tissues. Endoplasmic reticulum stress occurs when misfolded proteins accumulate in the endoplasmic reticulum. This triggers the unfolded protein response, a large transcriptional response which attempts to restore homeostasis. This transcriptional response, despite being a conserved, basic cellular process, is highly variable across different genetic backgrounds, making it an ideal system to study the dynamic effects of genetic variation. In this study, we sought to better understand how genetic variation alters expression across tissues, in the presence and absence of endoplasmic reticulum stress. The use of different mouse strains and their F1s allow us to also identify context-specific cis- and trans- regulatory variation underlying variable transcriptional responses. We found hundreds of genes that respond to endoplasmic reticulum stress in a tissue- and/or genotype-dependent manner. The majority of the regulatory effects we identified were acting in cis-, which in turn, contribute to the variable endoplasmic reticulum stress- and tissue-specific transcriptional response. This study demonstrates the need for incorporating environmental stressors across multiple different tissues in future studies to better elucidate the effect of any particular genetic factor in basic biological pathways, like the endoplasmic reticulum stress response.
Age and Physical Activity Levels in Companion Dogs: Results From the Dog Aging Project
Authors: Lee Hannah , Collins Devin , Creevy Kate E , Promislow Daniel E L ,   Dog Aging Project Consortium, Akey Joshua M , Benton Brooke , Borenstein Elhanan , Castelhano Marta G , Coleman Amanda E , Creevy Kate E , Crowder Kyle , Dunbar Matthew D , Fajt Virginia R , Fitzpatrick Annette L , Jeffery Unity , Jonlin Erica C , Kaeberlein Matt , Karlsson Elinor K , Kerr Kathleen F , Levine Jonathan M , Ma Jing , McClelland Robyn L , Promislow Daniel E L , Ruple Audrey , Schwartz Stephen M , Shrager Sandi , Snyder-Mackler Noah , Tolbert Katherine , Urfer Silvan R , Wilfond Benjamin S
Published: April 2022

While there has been an abundance of studies on the important relationship between physical activity and age in both dogs and humans, studies on dogs have primarily focused on how a dog’s biological characteristics, such as their weight, affect the age–activity relationship. To date, there is little knowledge about how this relationship may be associated with contextual- and owner-level characteristics. We leveraged a large and novel data set from the Dog Aging Project (DAP) to investigate the extent to which the age–activity relationship is associated with certain dog and owner characteristics, namely dog size, owner age, and the environment in which they live. Dogs are a unique model for aging research as they are exposed to similar social and environmental elements as humans but have a shorter life span, allowing researchers to observe their entire life course. We find that older dogs are less active than younger dogs; rural dogs are more active than suburban and urban dogs, especially at younger ages; and larger dogs are more active than smaller dogs. These findings are generally consistent with previous studies. However, a surprising finding is that older owners have more active dogs than younger owners. As one of the first studies to utilize the large survey data from the DAP, this study lays the foundation for future investigations to further understand and identify the biological, social, and environmental causes, as well as consequences, of aging.
Losartan Mitigates Oxidative Stress in the Brains of Aged and Inflamed IL-10−/− Mice
Authors: Saleh Nazaneen , Cosarderelioglu Caglar , Vajapey Ramya , Walston Jeremy , Abadir Peter M
Published: April 2022

Chronic inflammation, oxidative stress, and dysregulation of the renin–angiotensin system are closely linked, and their crosstalk commonly contributes to age-related physical and cognitive decline. The primary dementia-protective benefits of Angiotensin II type 1 receptor (AT1R) blockers are believed to arise from systemic effects on blood pressure. However, there is an independently regulated brain-specific renin–angiotensin system. Here, we examined the impact of 4 weeks of oral Losartan treatment on the brains of aged (100 weeks old) IL-10−/− mice, an animal model of chronic inflammation and frailty. Our data show that aged IL-10−/− mice have higher AT1R and Nitrotyrosine (oxidative stress marker) levels in their frontal cortex tissue but not in cerebellar or hippocampal tissue compared to age- and sex-matched wild type mice. Losartan treatment for 4 weeks is associated with lower AT1R protein level, Nitrotyrosine, and Tau protein in the frontal cortex of aged IL-10−/− mice. Our results highlight the impact of Losartan, an AT1R blocker commonly prescribed for treating high blood pressure, on the brain-specific angiotensin system and AT1R-linked downstream effects such as brain oxidative stress damage and Tau burden in a frailty mouse model.
Discrimination, Racial Identity, and Hypertension Among Black Americans Across Young, Middle, and Older Adulthood
Authors: Thomas Tobin Courtney S , Gutiérrez Ángela , Norris Keith C , Thorpe Roland J
Published: April 2022

Objectives

Substantial evidence documents the protective role of racial identity—or the meaning and significance that individuals attribute to race—among Black Americans, yet the impact of racial identity on physical health outcomes beyond young adulthood is unclear. To clarify the extent to which racial identity remains influential for physical health across the life course, this study investigated (a) the direct associations between discrimination, racial identity, and hypertension, (b) whether racial identity buffered the negative effects of discrimination, and (c) the extent to which these patterns varied among young (21–35), middle-aged (36–49), and older (>50) Black adults.

Methods

Data from the Nashville Stress and Health Study (N = 627) were used to examine two identity dimensions: “racial centrality” (i.e., importance of Black identity to one’s sense of self) and “closeness to other Black people” (COBP). Modified Poisson models estimated relationships between racial identity, discrimination, and hypertension. Interactions determined whether racial identity moderated the discrimination–hypertension association within and across age groups.

Results

High centrality and moderate COBP were directly linked to elevated hypertension odds among young adults, but lower odds among older adults; racial identity was not directly associated with hypertension among middle-aged adults. Results also indicated that racial identity conditioned the discrimination–hypertension relationship in distinct ways across age groups.

Discussion

Findings underscore the significance of racial identity as sources of both psychosocial vulnerability and resilience for minority aging. Clinicians and public health professionals should consider racial identity beyond young adulthood to promote healthy aging via hypertension management among Black Americans.
Cohort Trends in the Burden of Multiple Chronic Conditions Among Aging U.S. Adults
Authors: Bishop Nicholas J , Haas Steven A , Quiñones Ana R
Published: April 2022

Objectives

Multimorbidity, also referred to as multiple chronic conditions (MCCs), is the concurrent presence of 2 or more chronic health conditions. Increasing multimorbidity represents a substantial threat to the health of aging populations. Recent trends suggest greater risk of poor health and mortality among later-born cohorts, yet we are unaware of work examining cohort differences in multimorbidity among aging U.S. adults.

Methods

We examine intercohort variation in MCC burden in adults aged 51 years and older using 20 years (n = 33,598; 1998–2018) of repeated assessment drawn from the Health and Retirement Study. The index of MCCs included 9 chronic conditions (heart disease, hypertension, stroke, diabetes, arthritis, lung disease, cancer excluding skin cancer, high depressive symptoms, and cognitive impairment). We used linear mixed models with various approaches to estimate age/period/cohort effects to model intercohort patterns in MCC burden. We also explored variation in the specific conditions driving cohort differences in multimorbidity.

Results

More recent cohorts had greater MCC burden and developed multimorbidity at earlier ages than those born to prior generations. The burden of chronic conditions was patterned by life-course sociodemographic factors and childhood health for all cohorts. Among adults with multimorbidity, arthritis and hypertension were the most prevalent conditions for all cohorts, and there was evidence that high depressive symptoms and diabetes contributed to the observed cohort differences in multimorbidity risk.

Discussion

Our results suggest increasing multimorbidity burden among more recently born cohorts of aging U.S. adults and should inform policy to address diminishing health in aging populations.
Identification of shared loci associated with both Crohn’s disease and leprosy in East Asians
Authors: Jung Seulgi , Park Dohoon , Lee Ho-Su , Kim Yongjae , Baek Jiwon , Hwang Sung Wook , Park Sang Hyoung , Yang Suk-Kyun , Ye Byong Duk , Han Buhm , Sun Yonghu , Liu Hong , Zhang Furen , Liu Jianjun , Song Kyuyoung
Published: April 2022

Genome-wide association studies (GWAS) of Crohn’s disease (CD) in European and leprosy in Chinese population have shown that CD and leprosy share genetic risk loci. As these shared loci were identified through cross-comparisons across different ethnic populations, we hypothesized that meta-analysis of GWAS on CD and leprosy in East Asian populations would increase power to identify additional shared loci. We performed a cross-disease meta-analysis of GWAS data from CD (1621 cases and 4419 controls) and leprosy (2901 cases 3801 controls) followed by replication in additional datasets comprising 738 CD cases and 488 controls and 842 leprosy cases and 925 controls. We identified one novel locus at 7p22.3, rs77992257 in intron 2 of ADAP1, shared between CD and leprosy with genome-wide significance (P = 3.80 × 10−11) and confirmed 10 previously established loci in both diseases: IL23R, IL18RAP, IL12B, RIPK2, TNFSF15, ZNF365-EGR2, CCDC88B, LACC1, IL27, NOD2. Phenotype variance explained by the polygenic risk scores derived from Chinese leprosy data explained up to 5.28% of variance of Korean CD, supporting similar genetic structures between the two diseases. Although CD and leprosy shared a substantial number of genetic susceptibility loci in East Asians, the majority of shared susceptibility loci showed allelic effects in the opposite direction. Investigation of the genetic correlation using cross-trait linkage disequilibrium score regression also showed a negative genetic correlation between CD and leprosy (rg [SE] = −0.40[0.13], P = 2.6 × 10−3). These observations implicate the possibility that CD might be caused by hyper-sensitive reactions toward pathogenic stimuli.
Evaluating the potential of lignosulfonates and chitosans as alfalfa hay preservatives using in vitro techniques
Authors: Leon-Tinoco Angela Y , Annis Seanna L , Almeida Saulo T , Guimarães Bianca C , Killerby Marjorie , Zhang Jinglin , Wu Changqing , Perkins Lewis B , Ma Zhengxin , Jeong Kwangcheol C , Romero Juan J
Published: April 2022

Our objectives were to compare the antifungal activity of 5 lignosulfonates, and 2 chitosans against fungi isolated from spoiled hay, and assess the effects of an optimized lignosulfonate, chitosan, and propionic acid (PRP) on high-moisture alfalfa hay. In experiment 1, we determined the minimum inhibitory concentration and minimum fungicidal concentration of 4 sodium lignosulfonates, 1 magnesium lignosulfonate, 2 chitosans, and PRP (positive control) against Aspergillus amoenus, Mucor circinelloides, Penicillium solitum, and Debaromyces hansenii at pH 4 and 6. Among sodium lignosulfonates, the one from Sappi Ltd. (NaSP) was the most antifungal at pH 4. However, chitosans had the strongest fungicidal activity with the exception of M. circinelloides at both pH 4 and 6. PRP had more antifungal effects than NaSP and was only better than chitosans for M. circinelloides. In experiment 2, we evaluated the effects of 3 additives (ADV): optimized NaSP (NaSP-O, UMaine), naïve chitosan (ChNv, Sigma–Aldrich), and PRP on high-moisture alfalfa hay. The experimental design was a randomized complete block design replicated 5 times. Treatment design was the factorial combination of 3 ADV× 5 doses (0, 0.25, 0.5, 1, and 2% w/w fresh basis). Additives were added to 35 g of sterile alfalfa hay (71.5 ± 0.23% DM), inoculated with a mixture of previously isolated spoilage fungi (5.8 log cfu/fresh g), and aerobically incubated in vitro for 23 d (25°C). After incubation, DM losses were reduced by doses as low as 0.25% for both NaSP-O and PRP (x¯=1.61) vs. untreated hay (24.0%), partially due to the decrease of mold and yeast counts as their doses increased. Also, hay NH3-N was lower in NaSP-O and PRP, with doses as low as 0.25%, relative to untreated hay (x¯=1.13 vs. 7.80% of N, respectively). Both NaSP-O and PRP increased digestible DM recovery (x¯=69.7) and total volatile fatty acids (x¯=94.3), with doses as low as 0.25%, compared with untreated hay (52.7% and 83.8 mM, respectively). However, ChNv did not decrease mold nor yeast counts (x¯=6.59 and x¯=6.16 log cfu/fresh g, respectively) and did not prevent DM losses relative to untreated hay. Overall, when using an alfalfa hay substrate in vitro, NaSP-O was able to prevent fungal spoilage to a similar extent to PRP. Thus, further studies are warranted to develop NaSP-O as a hay preservative under field conditions.
Long-Term Laryngotracheal Complications After Inhalation Injury: A Scoping Review
Authors: Zhen Emily , Misso Dylan , Rea Suzanne , Vijayasekaran Shyan , Fear Mark , Wood Fiona
Published: April 2022

Long-term laryngotracheal complications (LTLC) after inhalation injury (II) are an under-recognized condition in patients with burns. The purpose of this study was to systematically review all available evidence on LTLC after II and identify gaps in knowledge to guide the direction of future research. A scoping review was performed to synthesize all available evidence on LTLC after II, as guided by the question, “What are the LTLC after II, in patients with or without a history of translaryngeal intubation and/or tracheostomy?”. MEDLINE, Web of Science, Ovid Embase, Cochrane Library, and Google Scholar were searched for publications on this topic. Of the 3567 citations screened, a total of 153 full-text articles were assessed for eligibility and 49 were included in the scoping review. The overall level of evidence was low, with case reports constituting 46.7% of all included human studies. The lesions were most frequently in the trachea (36.9%), followed by the glottis (34.7%) and subglottis (19.0%). LTLC occur in 4.8 to 6.5% of patients after II and these complications are under-recognized in burns patients. The risk factors for LTLC include high-grade II, elevated initial inflammatory responses, prolonged translaryngeal intubation, and a history of tracheostomy. The goal of management is to restore airway patency, preserve voice quality, and restore normal diet and swallow function. There is limited high-level evidence on LTLC, particularly with regards to long-term functional morbidity in voice and swallow. Large, prospective studies are required to address this gap in knowledge.
Can we do that here? An analysis of US federal and state policies guiding human embryo and embryoid research
Authors: Matthews Kirstin R W , Morali Daniel
Published: April 2022

Recent technological advances have helped scientists understand early human development. However, scientists’ ability to fully explore their potential comes in conflict with national and state-level policies in the USA. In 2016, for the first time, researchers were able to grow human embryos in culture up to 14 days but stopped because of scientific and legal limits. Other researchers have used stem cells in culture to create organized models of early human development, known as embryoids or cell-based embryo models. In this paper, we review federal and state laws that affect US human embryo and embryoid research. While federal policies focus on funding, state laws are often associated with human embryonic stem cells, abortion, fetal tissue research, and reproductive cloning. Of the 29 states with laws impacting human embryo research, only 11 states ban it, and none address embryoids directly, although five states limit aspects of this research. Overall, this complicated landscape suggests that additional national guidance would help scientists and the public navigate these controversial areas of research, however, it is unlikely to happen, considering the lack of past progress determining embryo research policy.
Obesity: an evolutionary context
Authors: Speakman John R , Elmquist Joel K
Published: April 2022

People completely lacking body fat (lipodystrophy/lipoatrophy) and those with severe obesity both show profound metabolic and other health issues. Regulating levels of body fat somewhere between these limits would, therefore, appear to be adaptive. Two different models might be contemplated. More traditional is a set point (SP) where the levels are regulated around a fixed level. Alternatively, dual-intervention point (DIP) is a system that tolerates fairly wide variation but is activated when critically high or low levels are breached. The DIP system seems to fit our experience much better than an SP, and models suggest that it is more likely to have evolved. A DIP system may have evolved because of two contrasting selection pressures. At the lower end, we may have been selected to avoid low levels of fat as a buffer against starvation, to avoid disease-induced anorexia, and to support reproduction. At the upper end, we may have been selected to avoid excess storage because of the elevated risks of predation. This upper limit of control seems to have malfunctioned because some of us deposit large fat stores, with important negative health effects. Why has evolution not protected us against this problem? One possibility is that the protective system slowly fell apart due to random mutations after we dramatically reduced the risk of being predated during our evolutionary history. By chance, it fell apart more in some people than others, and these people are now unable to effectively manage their weight in the face of the modern food glut. To understand the evolutionary context of obesity, it is important to separate the adaptive reason for storing some fat (i.e. the lower intervention point), from the nonadaptive reason for storing lots of fat (a broken upper intervention point). The DIP model has several consequences, showing how we understand the obesity problem and what happens when we attempt to treat it.
What Determines Consumer Financial Distress? Place- and Person-Based Factors
Authors: Keys Benjamin J , Mahoney Neale , Yang Hanbin
Published: April 2022

We use credit report data to study consumer financial distress in America. We report large, persistent disparities in financial distress across regions. To understand these patterns, we conduct a “movers” analysis. For collections and default, there is only weak convergence following a move, suggesting these types of distress are not primarily caused by place-based factors (e.g., local economic conditions and state laws) but instead reflect person-based characteristics (e.g., financial literacy and risk preferences). In contrast, for personal bankruptcy, we find a sizable place-based effect, which is consistent with anecdotal evidence on how local legal factors influence personal bankruptcy.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Efficacy and Safety of MSC Cell Therapies for Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis
Authors: Qu Wenchun , Wang Zhen , Engelberg-Cook Erica , Yan Dan , Siddik Abu Bakar , Bu Guojun , Allickson Julie G , Kubrova Eva , Caplan Arnold I , Hare Joshua M , Ricordi Camillo , Pepine Carl J , Kurtzberg Joanne , Pascual Jorge M , Mallea Jorge M , Rodriguez Ricardo L , Nayfeh Tarek , Saadi Samer , Durvasula Ravindra V , Richards Elaine M , March Keith , Sanfilippo Fred P
Published: April 2022

MSC (a.k.a. mesenchymal stem cell or medicinal signaling cell) cell therapies show promise in decreasing mortality in acute respiratory distress syndrome (ARDS) and suggest benefits in treatment of COVID-19-related ARDS. We performed a meta-analysis of published trials assessing the efficacy and adverse events (AE) rates of MSC cell therapy in individuals hospitalized for COVID-19. Systematic searches were performed in multiple databases through November 3, 2021. Reports in all languages, including randomized clinical trials (RCTs), non-randomized interventional trials, and uncontrolled trials, were included. Random effects model was used to pool outcomes from RCTs and non-randomized interventional trials. Outcome measures included all-cause mortality, serious adverse events (SAEs), AEs, pulmonary function, laboratory, and imaging findings. A total of 736 patients were identified from 34 studies, which included 5 RCTs (n = 235), 7 non-randomized interventional trials (n = 370), and 22 uncontrolled comparative trials (n = 131). Patients aged on average 59.4 years and 32.2% were women. When compared with the control group, MSC cell therapy was associated with a reduction in all-cause mortality (RR = 0.54, 95% CI: 0.35-0.85, I  2 = 0.0%), reduction in SAEs (IRR = 0.36, 95% CI: 0.14-0.90, I  2 = 0.0%) and no significant difference in AE rate. A sub-group with pulmonary function studies suggested improvement in patients receiving MSC. These findings support the potential for MSC cell therapy to decrease all-cause mortality, reduce SAEs, and improve pulmonary function compared with conventional care. Large-scale double-blinded, well-powered RCTs should be conducted to further explore these results.
Rapid Decline of Calonectria pseudonaviculata Soil Population in Selected Gardens Across the United States
Authors: Hong Chuanxue , Daughtrey Margery , Howle Matthew , Schirmer Scott , Kosta Kathleen , Kong Ping , Likins Michael , Suslow Karen
Published: April 2022

Calonectria pseudonaviculata (Cps) poses a serious threat to boxwood, an iconic landscape plant in American and European gardens. Under the mild climatic conditions of the United Kingdom, Cps remained recoverable in infected leaf debris after being left on the soil surface or buried for 5 years. The primary objective of this study was to determine how this fungus may be affected by the warmer summers and colder winters in the United States by sampling and baiting soil with boxwood cuttings and by on-site testing with sentinel plants. Soil sampling started in a Virginia garden in January 2016 and was extended to California, Illinois, New York, and South Carolina in early summer of 2017 through late fall of 2018. The Cps soil population as measured by the percentage of infected bait leaves declined sharply within the first year of blighted boxwood removal and fell to an almost undetectable level at the end of this study. To validate these baiting results, the Virginia garden was tested on site four times with container-grown boxwood plants while the South Carolina garden and three New York gardens were tested once. Each test began with sentinel plants set out for field exposure, followed by evaluation on site and then in the laboratory after plants were retrieved from these gardens and incubated under conducive environments for 2 weeks. Cps was not observed on any sentinel boxwood plant on site or in the laboratory with one exception. These observations indicate that Cps did not survive in the United States garden soil over time as well as it did in the United Kingdom. These results have important practical implications while challenging the notion that fungi producing microsclerotia will always survive in the soil for many years.
Clinical Correlates of Depression and Suicidality in Huntington Disease: An Analysis of the Enroll-HD Observational Study
Authors: Rocha Natalia P. , Tuazon Madison R. , Patino Jorge , Furr Stimming Erin , Teixeira Antonio L.
Published: April 2022

Background:

Depression and suicidality are commonly experienced by Huntington disease (HD) gene carriers. Research on these behavioral symptoms is imperative, not only to increase our understanding of the symptoms and how they relate to HD, but also to contribute to improving patients’ care and quality of life.

Objective:

To identify clinical variables associated with a history of depression and suicidality in HD gene carriers.

Method:

We conducted a cross-sectional study of HD gene carriers from the Enroll-HD database PDS4 (periodic data set 4; N = 11,582). Data from baseline visits were obtained, and binary logistic regression models were used to ascertain the effects of clinical variables on the likelihood that HD gene carriers would have previous depression and suicidal ideation/attempts.

Results:

Approximately 65% (n = 7526) of the HD gene carriers had a history of depression, and ~27% (n = 3152) had previous suicidal ideation/attempts. Female sex; diagnosis of manifest HD; history of perseverative/obsessive behavior, apathy, and psychosis; and previous suicidal ideation/attempts were significantly associated with a history of depression in the HD gene carriers. Medical history of apathy, psychosis, and depression, as well as worse scores on the Total Functional Capacity and Irritability Scales, were significantly associated with previous suicidal ideation/attempts in the HD gene carriers.

Conclusion:

The prevalence of depression and suicidality is high among HD gene carriers. An improved understanding of the risk factors for depression and suicide in HD gene carriers can assist providers in recognizing at-risk individuals and allow providers to implement therapeutic strategies.
Delirium as a Presenting Symptom of COVID–19
Authors: Tyson Brad , Shahein Ayman , Erdodi Laszlo , Tyson Leigh , Tyson Robert , Ghomi Reza , Agarwal Pinky
Published: April 2022

Background:

Delirium is a common neurologic manifestation of coronavirus disease 2019 (COVID–19) in older adults who present to the emergency department (ED).

Objective:

To investigate clinical characteristics associated with delirium as a presenting symptom of COVID–19 in older adults and develop a logistic regression to predict the likelihood of delirium.

Method:

We compared clinical characteristics in an age- and gender-matched sample of 68 delirious individuals with 68 nondelirious individuals (Mage = 78) who presented to the ED with COVID–19.

Results:

The delirious group was more likely to have neurologic, psychiatric, and cardiovascular comorbidities; a prior history of delirium; and deliriogenic medications in their medication list. They were less likely to present with respiratory symptoms and more likely to present with sepsis, hypoxia, higher heart rate, and higher sodium. The delirious group had higher mortality (51%) than the nondelirious group (32%). Delirium developed within an average of 2 days of initial COVID–19 symptom onset, with symptom onset to ED within an average of 4 days and symptom onset to death within an average of 11 days. Logistic regression based on five delirium predictors correctly predicted 80% of those with delirium (75% sensitivity at 86% specificity).

Conclusion:

Our results are largely consistent with prior studies and suggest that delirium is a common, early occurring, and lethal manifestation of COVID–19 in older adults presenting to the ED, in most cases causing acute on chronic neurocognitive dysfunction strongly influenced by inflammatory and hypoxic–ischemic mechanisms.
Dengue and Chikungunya virus circulation in Cameroon and Gabon: molecular evidence among symptomatic individuals
Authors: Djeunang Dongho Ghyslaine Bruna , Venturi Giulietta , Fortuna Claudia , Paganotti Giacomo Maria , Severini Carlo , L’Episcopia Mariangela , Tsapi Armand Tiotsia , Benedetti Eleonora , Marsili Giulia , Amendola Antonello , Rezza Giovanni , Sobze Martin Sanou , Russo Gianluca
Published: April 2022

We report the molecular evidence of dengue virus (DENV) and chikungunya virus (CHIKV) infection in symptomatic individuals in Cameroon and Gabon, respectively. Arthropod-borne viruses (arboviruses) are distributed in the tropical or subtropical regions, with DENV having the highest burden. The morbidity and mortality related to arboviral diseases raise the concern of timely and efficient surveillance and care. Our aim was to assess the circulation of arboviruses [DENV, CHIKV, Zika virus (ZIKV)] among febrile patients in Dschang (West Cameroon) and Kyé-ossi (South Cameroon, border with Gabon and Equatorial Guinea). Dried blood spots were collected from 601 consenting febrile patients, and 194 Plasmodium spp.-negative samples were tested for the molecular detection of cases of DENV, CHIKV and ZIKV infection. Overall, no case of ZIKV infection was found, whereas one case of DENV infection and one case of CHIKV infection were detected in Dschang and Kyé-ossi, respectively, with the CHIKV-infected patient being resident in Gabon. Our findings suggest the need to establish an active surveillance of arbovirus transmission in Cameroon and bordering countries.
Real-time monitoring of endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation
Authors: Harish Rohit Krishnan , Gupta Mansi , Zöller Daniela , Hartmann Hella , Gheisari Ali , Machate Anja , Hans Stefan , Brand Michael
Published: April 2022

Morphogen gradients impart positional information to cells in a homogenous tissue field. Fgf8a, a highly conserved growth factor, has been proposed to act as a morphogen during zebrafish gastrulation. However, technical limitations have so far prevented direct visualization of the endogenous Fgf8a gradient and confirmation of its morphogenic activity. Here, we monitored Fgf8a propagation in the developing neural plate using a CRISPR/Cas9-mediated EGFP knock-in at the endogenousfgf8alocus. By combining sensitive imaging platforms with single-molecule Fluorescence Correlation Spectroscopy (FCS), we demonstrate that Fgf8a, produced at the embryonic margin, propagates by free diffusion through the extracellular space and forms a graded distribution towards the animal pole. Overlaying the Fgf8a gradient curve with expression profiles of its downstream targets determines the precise input-output relationship of Fgf8a mediated patterning. Manipulation of the Fgf8a input alters the signaling outcome, thereby establishing Fgf8a as a bona fide morphogen during zebrafish gastrulation. Furthermore, using diffusion-hindered versions of Fgf8a, we demonstrate that extracellular diffusion of the protein from the source is critical for it to achieve its morphogenic potential.
Chemotherapy Signatures Map Evolution of Therapy-Related Myeloid Neoplasms
Authors: Diamond Benjamin , Ziccheddu Bachisio , Maclachlan Kylee , Taylor Justin , Boyle Eileen , Ossa Juan Arrango , Jahn Jacob , Affer Maurizio , Totiger Tulasigeri M. , Coffey David , Watts Justin , Lu Sydney X , Bolli Niccolò , Bolton Kelly , Park Jae H. , Landau Heather , Ganesh Karuna , McPherson Andrew , Sekeres Mikkael A. , Lesokhin Alexander , Chung David , Zhang Yanming , Ho Caleb , Roshal Mikhail , Tyner Jeffrey , Nimer Stephen , Papaemmanuil Elli , Usmani Saad , Morgan Gareth , Landgren Ola , Maura Francesco
Published: April 2022

Patients treated with cytotoxic therapies, including autologous stem cell transplantation, are at risk for developing therapy-related myeloid neoplasms1, 2. Pre-leukemic clones (i.e., clonal hematopoiesis) are detectable years before the development of these aggressive malignancies3-5, though the genomic events leading to transformation and expansion are not well-defined. Here, leveraging distinctive chemotherapy-associated mutational signatures6-12 from whole-genome sequencing data and targeted sequencing of pre-chemotherapy samples, we reconstruct the evolutionary life-history of 39 therapy-related myeloid malignancies. A dichotomy is revealed, in which neoplasms with evidence of chemotherapy-induced mutagenesis from platinum and melphalan are relatively hypermutated and enriched for complex structural variants (i.e., chromothripsis), while neoplasms with alternative exposures bear a similar profile to de novo acute myeloid leukemia. Using chemotherapy-associated mutational signatures as a temporal barcode in each patient’s life, we estimate that several complex events and genomic drivers are acquired after chemotherapy exposure. In the case of treatment with high-dose melphalan and autologous stem cell transplantation, we demonstrate that the procedure allows clonal hematopoiesis to escape chemotherapy exposure entirely, and to be reinfused to expand to malignancy. This information reveals a novel mode of malignant progression for therapy-related malignancies that is not reliant on direct mutagenesis or even exposure to chemotherapy, itself, and prompts further investigation into leukemia-permissive effects of cytotoxic drugs.