bluuebunny/crossref_metadata_2025 huggingface dataset:
Acupuncture for treating chronic spinal pain: A systematic review and meta-analysis protocol
Authors: Li Xingye , Han Xiao , Li Kuan
Published: December 2022

Background:

Chronic spinal pain is one of the most leading causes of disability among adults worldwide and is associated with significant health care use. The effect of acupuncture on chronic spinal pain seems controversial based on evidence-based perspective. Thus, we performed a protocol for systematic review and meta-analysis to evaluate the effectiveness of acupuncture for treatment of chronic spinal pain.

Methods:

This systematic review has been registered in PROSPERO (CRD42019120665), which will be conducted in accordance with preferred reporting items for systematic review and meta-analysis protocols 2015 statement. We will search 7 electronic databases to identify relevant studies from inception to November, 2022, which includes PubMed, MEDLINE, Embase, Cochrane Clinical Trials Database, Web of Science, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database. Cochrane “bias risk” tool is used to assess the bias risk of the quality of the included literature. RevMan V.5.3 software will be used to analyze all data.

Results:

A synthesis of current evidence of acupuncture for treating chronic spinal pain will be provided in this protocol.

Conclusion:

This review will provide directions and recommendations for future research and clinical practices of acupuncture for treating chronic spinal pain.
Safety of prescribed herbal medicines for hepatic and renal function of polypharmacy patients with stroke: A single-center retrospective study
Authors: Kim JunSeok , Jang WooSeok
Published: December 2022

In Korea, herbal medicines (HMs) are primarily used to treat diseases. Patients with stroke are generally older and take several conventional medicines (CMs) to address other underlying diseases, which is known as polypharmacy. Therefore, there is a growing concern about hepatotoxicity and nephrotoxicity due to drug interactions between HMs and CMs. Therefore, this study retrospectively investigated liver and renal tests in patients with stroke treated with polypharmacy to clarify the safety of simultaneous HM and CM administration. The medical records of 111 patients with stroke treated at a single center and who met the inclusion criteria between March 1, 2017, and March 1, 2022, were reviewed. The HMs and HM prescription frequency, CMs, and liver and kidney test results were recorded. Additionally, the Roussel Uclaf Causality Assessment Method and Kidney Disease Improving Global Outcome scores were documented, which are standard criteria for assessing liver and kidney injury, respectively. The study included 53 men and 58 women (average age: 67.8 years). On average, the patients took 6 types of CMs. No patient showed liver injury during the co-administration of CMs and HMs. Only 1 patient had initial hepatic damage but recovered after taking HMs. Furthermore, 2 patients had liver test abnormalities 2 times the upper limit of normal, possibly from Seogyeong-tang and atorvastatin, with Roussel Uclaf Causality Assessment Method scale scores of 3 and 5, respectively. No patient had a renal injury. HM is safe for patients with stroke taking multiple CMs. However, consulting an HM expert is essential to avoid hepatotoxicity, nephrotoxicity, and other adverse effects. These results highlight the benefits of Korea’s dual medical system.
Epidemiologic and clinical characteristics of selected congenital anomalies at the largest Bosnian pediatric surgery tertiary center
Authors: Zvizdic Zlatan , Becirovic Naida , Milisic Emir , Jonuzi Asmir , Terzic Sabina , Vranic Semir
Published: December 2022

Congenital anomalies (CA) are any abnormality present at birth, either structural or functional, that may potentially affect an infant’s health, development, and/or survival. There is a paucity of studies on clinical characteristics and outcomes of CA in Bosnia and Herzegovina, mainly due to the lack of a nationwide congenital malformations monitoring system. A 5-year hospital-based study was conducted to determine the prevalence at birth and clinical characteristics of selected major CA in Sarajevo Canton, Bosnia and Herzegovina. Ninety-one CA were observed from 2012 to 2016 (the overall prevalence was 39.6 cases/10,000 live births). The mean age of neonates at diagnosis was 3 days. The gastrointestinal tract was the most commonly affected system (76.9%), with esophageal atresia (EA) being the most frequent (17.6% of all CA). Major CA were more prevalent among preterm infants than term infants (P = .001), particularly in males (61.5% vs. 38.5%; P = .028; M:F ratio was 1.59). Multiple CA were seen in 37.4% of neonates. The overall mortality rate of neonates was 11%, and the median length of hospital stay was 19.8 days. Our study revealed the distribution and clinical patterns of common major CA in the largest tertiary care facility in Bosnia and Herzegovina. It also confirmed a relatively high mortality rate, which requires further efforts to improve the quality of neonatal care in the country.
Diabetes mellitus in Bardet Biedl syndrome
Authors: Pomeroy Jeremy , Offenwanger Kelsi-Marie , Timmler Tammi
Published: December 2022

Purpose of review

Bardet Biedl syndrome (BBS) is a rare disease characterized by obesity and hyperphagia. Despite the very high prevalence of paediatric and adult obesity in this population, the prevalence of diabetes mellitus is not well described.

Recent findings

Studies in small and moderately large cohorts suggest a high prevalence of traditional risk factors for diabetes mellitus in people with BBS. People with BBS appear to have a high prevalence of insulin resistance and metabolic syndrome. Small cohort studies have identified high rates of sleep disordered breathing, including sleep apnoea syndrome. Recent research has characterized traditional behavioural risk factors such as sleep hygiene and physical inactivity in people with BBS. High rates of insufficient sleep and prolonged sedentary time suggest behavioural targets of interventions to treat or prevent diabetes mellitus. Hyperphagia, likely caused by defects in the hypothalamic melanocortin-4 receptor (MC4R) neuronal pathway, pose additional challenges to behavioural interventions to prevent diabetes mellitus.

Understanding the prevalence of diabetes mellitus and other metabolic disorders in people with BBS and the impact of traditional risk factors on glucose regulation are important to developing effective treatments in this population.
Carpal Tunnel Syndrome as a Test Case for Value Assessment During the Presurgical Period
Authors: Sears Erika D. , Evans Richard , Burns Jennifer , Chung Kevin C. , Hayward Rodney A. , Kerr Eve A.
Published: December 2022

Background:

Few performance measures assess presurgical value (quality and utilization).

Objectives:

Using carpal tunnel syndrome (CTS) as a case study: (1) develop a model to evaluate presurgical quality and utilization and (2) identify opportunities for value improvement.

Research Design:

A retrospective cohort study utilizing Veterans Affairs (VA) national administrative data.

Subjects:

Patients who were evaluated in a VA primary care clinic on at least 1 occasion for CTS and received carpal tunnel release over a 7-year period.

Measures:

We modeled facility-level performance on 2 outcomes: surgical delay (marker of quality) and number of presurgical encounters (utilization) for CTS, and examined association between patient, facility, and care process variables and performance.

Results:

Among 41,912 Veterans undergoing carpal tunnel release at 127 VA medical centers, the median facility-level predicted probability of surgical delay was 48%, with 16 (13%) facilities having significantly less delay than the median and 13 (10%) facilities having greater delay. The median facility-level predicted number of presurgical encounters was 8.8 visits, with 22 (17%) facilities having significantly fewer encounters and 22 (17%) facilities having more. Care processes had a stronger association with both outcomes than structural variables included in the models. Processes associated with the greatest deviations in predicted delay and utilization included receipt of repeat electrodiagnostic testing, use of 2 or more nonoperative treatments, and community referral outside of VA.

Conclusions:

Using CTS as a test case, this study demonstrates the potential to assess presurgical value and identify modifiable care processes associated with presurgical delay and utilization performance.
The Hematology Cancer Patient Experience of “Facing Death” in the Last Year of Life
Authors: Campbell Karen , Harris Fiona , Stoddart Kathleen
Published: December 2022

Background

For hematology cancer patients, the process of dying is described as “troublesome.” Qualitative studies have focused on views of healthcare professionals and caregiver stakeholders. To date, there have been no studies from the patient’s perspective on facing death while in the last year of life.

Objective

The aim of this study was to develop an understanding of the hematology cancer patient’s experience of the process of dying in the last year of life.

Methods

The study method was constructivist grounded theory using semistructured interviews, a constant comparison technique, and memoing to collection and analysis of data. The 21 participants were attending a UK cancer center, a cancer unit, or a hospice.

Results

This article describes 1 core category within the incurable hematology cancer illness trajectory through 4 subcategories: transitional phase, chronic phase, dying phase, and liminal phase.

Conclusion

This unique study illustrates that, although life can be prolonged, “facing death” still occurs upon hospitalization and relapse regularly over the illness trajectory.

Implications for Practice

It is important that clinical practice acknowledges those participants in an incurable illness trajectory while living are focused on avoiding death rather than the ability to cure the disease. Services need to be responsive to the ambiguity of both living and dying by providing holistic management simultaneously, especially after critical episodes of care, to enhance the process of care in the last year of life, and assessment should incorporate the discussion of experiencing life-threatening events.
An overview of programmatic indicators to monitor the roll-out of HIV preexposure prophylaxis
Authors: Wijstma Eline , Vanhamel Jef , Deblonde Jessika , Nöstlinger Christiana , Noori Teymur , Vuylsteke Bea , Laga Marie
Published: December 2022

Preexposure prophylaxis (PrEP) is increasingly implemented in national HIV prevention programmes through routine care. Monitoring will be vital to understand whether programmes succeed in engaging people into using PrEP appropriately, and in reducing the HIV epidemic. Yet, it is currently unclear which indicators are most suited to monitor PrEP programmes’ performance. We therefore aimed to identify and map indicators that are currently used or suggested for monitoring PrEP programmes. We conducted a scoping review based on the framework by Arksey and O’Malley. We combined a systematic search in the peer-reviewed literature with hand-searching grey literature documents describing indicators and strategies that are used or suggested for PrEP monitoring. Only literature published after 2012 was included. No geographical restrictions were set. We charted data on indicator definitions, data sources used, reported experiences with monitoring and any relevant contextual factors. Ultimately, 35 peer-reviewed and 14 grey literature records were included. We identified indicators related to preuptake stages of PrEP, uptake and coverage, and programme impact. The indicators most commonly suggested for national-level monitoring were the number of new and current PrEP users, the number of HIV seroconversions among PrEP users and some variably defined indicators related to continuation and discontinuation of PrEP. Despite its perceived high relevance, studies reported several challenges to routinely monitor the population in need of PrEP and track prevention-effective PrEP use. In conclusion, a variety of indicators is currently used or suggested for monitoring PrEP programmes. Implementing proxy measures that track different aspects of PrEP use over time, and making synergies with research more explicit, could be used as strategies to obtain more granular insights into trends revealed by routine monitoring.
Kidney-transplanted Adolescents—Nonadherence and Graft Outcomes During the Transition Phase: A Nationwide Analysis, 2000–2020
Authors: Kindem Ingvild A. , Bjerre Anna , Hammarstrøm Clara , Naper Christian , Midtvedt Karsten , Åsberg Anders
Published: December 2022

Background.

The transition from pediatric to young adult care is a vulnerable period for the renal transplant patient. We aimed to identify medication nonadherence (noninitiation, nonimplementation, and nonpersistence) and graft loss rates among adolescents and young adults and elucidate the influence of the transition phase on transplant outcomes.

Methods.

A retrospective nationwide cohort analysis of all renal transplantations in Norway from 2000 to 2020 was performed. Data were retrieved from the Norwegian Renal Registry, and adherence data from hospital charts. Patients transplanted aged <50 y, with functioning graft at 6 mo, were included. Recipients transplanted aged <26 y were compared with recipients transplanted aged 26–50 y. Graft loss, acute rejection, and development of de novo donor-specific antibodies were assessed in relation to the transition phase, defined as 14–26 y.

Results.

Data from 1830 kidney recipients were included: 371 (20%) transplanted <26 y (64% male, 68% living donor) versus 1459 transplanted 26–50 y (63% male, 44% living donor). There were 298 graft losses, 78 (21%) in the <26-y group versus 220 (15%) in the 26- to 50-y group. During the transition phase, 36 grafts were lost, 29 (81%) after transfer to the adult service. Medication nonadherence was the reason for 58% (21 of 36) of the losses during the transition phase, versus 12% (27 of 220) in the 26- to 50-y group (P < 0.001). The 5-y graft survival rate was 89% (95% confidence interval, 85%-92%) and 94% (92%-95%), respectively (P = 0.01).

Conclusions.

Nonadherence was verified as the main cause of kidney graft loss in the transition phase.
Effect Modification on Death by Age and Sex in Elderly Hip Fracture
Authors: Jang Suk-Yong , Cha Yonghan , Park Na-Kyum , Kim Kap-Jung , Choy Won-Sik
Published: December 2022

Background: This study compared the effects of hip fractures on mortality according to sex and age in a nationwide cohort of elderly patients with hip fractures and controls.Methods: Patients with hip fractures and matched controls were selected from the National Health Insurance Service-Senior cohort. Time-dependent propensity score matching was estimated from a Cox proportional hazards model with January 1, 2005, as the baseline and hip fracture as an event. Patients were matched by age and sex to participants at risk of developing a hip fracture at time zero. The effect size is presented as hazard ratio (HR) using a Cox proportional hazards model with a robust variance estimator that accounts for clustering within the matched pairs.Results: Altogether, 14,283 patients with incident hip fractures and 28,566 matched controls were identified. The HR of male sex in hip fractures was 1.31 (95% confidence interval [CI], 1.22−1.40; Pinteraction<0.01). Moreover, the HR of age group in hip fractures was 0.73 (95% CI, 0.66−0.80; Pinteraction<0.01) between the 65 to 74 and 75 to 84 years groups, 0.76 (95% CI, 0.71−0.81; Pinteraction<0.01) between the 75 to 84 and ≥85 years groups, and 0.55 (95% CI, 0.50−0.61; Pinteraction<0.01) between the 65 to 74 and ≥85 years groups.Conclusions: Male sex increases the risk of death in elderly patients with hip fractures versus matched controls, but the increased risk of death with age in hip fractures was decreased compared to that in matched controls.
Five-Year Assessment of Multiple Gene Variants Associated with Bone Marrow Hypocellularity, Reduced Bone Density, and Ovarian Insufficiency in Adolescence
Authors: Sills E. Scott , Harrity Conor , Wood Samuel H.
Published: December 2022

This study covers the 5-year interval prior to COVID-19 admission for an otherwise healthy 46,XX adolescent expanding the developmental characterization of an unusual convergence of amenorrhea and genetic mutations. The patient experienced rapid collapse of endogenous estradiol output followed by secondary amenorrhea at 13 years of age. Euploid, diffusely hypocellular bone marrow was present on biopsy, although anemia or reduced total immunoglobulin production was not identified. Bone density was 1.5 years below mean; multiple dental anomalies were also documented. While alterations in “master regulator” genes RUNX2, SALL1, and SAMD9 are usually diagnosed in early childhood when missed milestones, dysmorphic features, or chronic infection/immune impairment warrant cross-disciplinary evaluation, this study is the first known report to associate ovarian failure with adolescence with such variants. Immunoglobulin patterns, osseous histomorphology, dentition, hematology/renal screening, pelvic anatomy, ovarian reserve data, and thyroid findings are also correlated. Although severe pathology is typically encountered when any of these genes are disrupted alone, this longitudinal survey reveals that a mild phenotype can prevail if these 3 variants occur simultaneously. Periodic monitoring is planned given the unclassified status of this unique mutation set.
Selective IgA2deficiency in a patient with small intestinal Crohn’s disease
Authors: Canales-Herrerias Pablo , Garcia-Carmona Yolanda , Meringer Hadar , Martinez-Delgado Gustavo , Tankelevich Michael , Colombel Jean-Frederic , Cunningham-Rundles Charlotte , Cerutti Andrea , Mehandru Saurabh
Published: December 2022

The human IgA response is composed of two structurally different subclasses termed IgA1and IgA2. Compared to IgA1, IgA2has a shorter hinge region, which makes it more resistant to bacterial proteases. IgA1is produced both systemically and in mucosal surfaces, whereas IgA2is mostly confined to the intestines. While the overall IgA response is known to be involved in intestinal homeostasis, the specific contribution of IgA1and IgA2remains largely unknown (Chen 2020). Selective IgA deficiency (SIgAD) is the most prevalent primary immune deficiency. About half of SIgAD cases are associated with heterogeneous but generally mild clinical manifestations. Anecdotal evidence of IgA2deficiency is available (van Loghem 1983, Ozawa 1986, Engström 1990), however no associations with clinical manifestations have been reported.

Here, we describe the occurrence of a selective IgA2deficiency in a patient (CD068) with small intestinal Crohn’s disease (CD). The patient had undetectable IgA2+cells and secreted IgA2antibody in both intestine and circulation. Among other features, patient CD068 presented with duodenal and ileal inflammation. To our knowledge, this is the first case of IgA2deficiency with a potential link to IBD, which might shed new insights into potential IgA2-specific functions.
Long-Term Ecological Responses of a Dipterocarp Forest to Climate Changes and Nutrient Availability
Authors: Prohaska Ana , Seddon Alistair W.R. , Rach Oliver , Smith Andrew , Sachse Dirk , Willis Katherine J.
Published: December 2022

Understanding the long-term impact of projected climate change on tropical rainforests is critical given their central role in the Earth’s system. Palaeoecological records can provide a valuable perspective on this problem. Here we examine for the first time the effects of past climatic changes on the dominant forest type of Southeast Asia – Dipterocarp forest.

We use a range of proxies extracted from a 1,400-year-old lacustrine sedimentary sequence from north-eastern Philippines to model long-term vegetation responses of Dipterocarp forest, including its dominant tree group Dipterocarps, to changes in precipitation, fire and nutrient availability over time.

Our results show a positive relationship between Dipterocarps pollen accumulation rates (PARs) and leaf wax hydrogen isotope values, which suggests a negative effect of drier conditions on Dipterocarp tree abundance. Furthermore, we find a positive relationship between Dipterocarp PARs and the proxy for phosphorus availability, which suggests phosphorus controls the productivity of these keystone trees on longer time scales. Other plant taxa show widely varying relationships with the abiotic factors, demonstrating a high diversity of functional responses.

Our findings provide novel insights into Dipterocarp forest responses to changing climatic conditions in the past, and highlight potential impacts of future climate change on this globally important ecosystem.
Nationwide assessment of leadership development for graduate students in the agricultural plant sciences
Authors: Da Silva Karen Ferreira , Burnham Ella , Louis Joe , Golick Douglas , Everhart Sydney
Published: December 2022

Leadership development is a universally important goal across the agricultural plant science disciplines. Although previous studies have identified a need for leadership skills, less is known about leadership skill development in graduate programs. To address this, we constructed a mixed-method study to identify the most significant graduate school leadership experiences of scientists in the agricultural plant science disciplines. The survey was deployed to 6,728 people in the U.S. and received 1,086 responses (16.1% response rate). The majority of respondents reported that they were from one of the major agricultural states and employed at one of the agricultural plant science related doctoral universities, industries, or government. Results from this survey suggest that recent graduates were more engaged in graduate school activities that offered leadership development. Key experiences in graduate school were also identified that may be used to develop future leaders. Additionally, respondents reported the greatest barrier to providing leadership development for graduate students was that it is not part of their program curriculum, however current graduate students responded differently, and identifying lack of funding to support experiences as the greatest barrier. This survey also identified the top ranked professional skills considered most important for effective leaders in agricultural plant sciences as well as respondent-driven recommendations on how graduate programs can improve leadership development. Collectively, these results can be used in the future to identify priorities for skill development and opportunities for graduate student training in leadership skills within the plant science disciplines.
Investigating the outcomes of virus coinfection within and across host species
Authors: Imrie Ryan M. , Walsh Sarah K. , Roberts Katherine E , Lello Joanne , Longdon Ben
Published: December 2022

Interactions between coinfecting pathogens have the potential to alter the course of infection and can act as a source of phenotypic variation in susceptibility between hosts. This phenotypic variation may influence the evolution of host-pathogen interactions within host species and interfere with patterns in the outcomes of infection across host species. Here, we examine experimental coinfections of twoCripaviruses– Cricket Paralysis Virus (CrPV), and Drosophila C Virus (DCV) –across a panel of 25Drosophila melanogasterinbred lines and 47Drosophilidaehost species. We find that interactions between these viruses alter viral loads acrossD. melanogastergenotypes, with a ~3 fold increase in the viral load of DCV and a ~2.5 fold decrease in CrPV in coinfection compared to single infection, but we find little evidence of a host genetic basis for these effects. Across host species, we find no evidence of systematic changes in susceptibility during coinfection, with no interaction between DCV and CrPV detected in the majority of host species. These results suggest that phenotypic variation in coinfection interactions within host species can occur independently of natural host genetic variation in susceptibility, and that patterns of susceptibility across host species to single infections can be robust to the added complexity of coinfection.
Autorepression-based conditional gene expression system in yeast for variation-suppressed control of protein dosage
Authors: Azizoğlu Aslı , Loureiro Cristina , Venetz Jonathan , Brent Roger
Published: December 2022

Conditional control of gene expression allows an experimenter to investigate many aspects of a gene’s function. In the model organismSaccharomyces cerevisiae, a number of methods to control gene expression are widely practiced, including induction by metabolites, small molecules, and even light. However, all current methods suffer from at least one of a set of drawbacks, including need for specialized growth conditions, leaky expression, or the requirement of specialized equipment. Here we describe protocols using two transformations to construct strains that carry a new controller, in which all these drawbacks are overcome. In these strains, the expression of a controlled gene (gene of interest, or GOI) is repressed by the bacterial repressor TetR, and induced by anhydrotetracycline. TetR also regulates its own expression, creating an autorepression loop. This autorepression allows tight control of gene expression/ protein dosage with low cell to cell variation in expression. A second repressor, TetR-Tup1, prevents any leaky expression. We also present a protocol showing a particular workhorse application of such strains, to generate synchronized cell populations. We turn off the expression of the cell cycle regulatorCDC20completely, arresting the cell population, and then back on so that the synchronized cells resume cell cycle progression. This control system can be applied to any endogenous or exogenous gene for precise expression.

Basic Protocol 1

Generating a parent WTC846strain.

Basic Protocol 2

Generating a WTC846strain with controlled expression of the targeted gene

Alternate Protocol 1

CRISPR-mediated promoter replacement

Basic Protocol 3

Cell cycle synchronization/Arrest and Release using the WTC846-K3::CDC20 strain
Uncovering the genomic basis of infection through co-genomic sequencing of hosts and parasites
Authors: Dexter Eric , Fields Peter D. , Ebert Dieter
Published: December 2022

Understanding the genomic basis of infectious disease is fundamental objective in coevolutionary theory with relevance to healthcare, agriculture, and epidemiology. Models of host-parasite coevolution often assume that infection requires specific combinations of host and parasite genotypes. Coevolving host and parasite loci are therefor expected to show associations that reflects an underlying infection/resistance allele matrix, yet little evidence for such genome-to-genome interactions has been observed among natural populations. We conducted a study to search for this genomic signature across 258 linked host (Daphnia magna)and parasite (Pasteuria ramosa)genomes. Our results show a clear signal of genomic association between multiple epistatically-interacting loci in the host genome, and a family of genes encoding for collagen-like protein in the parasite genome. These findings are supported by laboratory-based infection trials, which show strong correspondence between phenotype and genotype at the identified loci. Our study provides clear genomic evidence of antagonistic coevolution among wild populations.
★Track: Inferred counting and tracking of replicating DNA loci
Authors: Köhler Robin , Sadhir Ismath , Murray Seán M.
Published: December 2022

Fluorescent microscopy is the primary method to study DNA organization within cells. However the variability and low signal-to-noise commonly associated with live-cell time lapse imaging challenges quantitative measurements. In particular, obtaining quantitative or mechanistic insight often depends on the accurate tracking of fluorescent particles. Here, we present★Track, an inference method that determines the most likely temporal tracking of replicating intracellular particles such DNA loci while accounting for missing, merged and spurious detections. It allows the accurate prediction of particle copy numbers as well as the timing of replication events. We demonstrate★Track’s abilities and gain new insight into plasmid copy number control and the volume dependence of bacterial chromosome replication initiation. By enabling the accurate tracking of DNA loci,★Track can help to uncover the mechanistic principles of chromosome organisation and dynamics across a range of systems.

Significance

Microscopy is one of the main tools for studying the intracellular organisation of cells. In particular, fluorescent proteins allow us to study the dynamics of many cellular processes. However, this requires the accurate tracking of fluorescent foci. Here, we present★Track a tool tailored to the tracking of replicating persistent subcellular particles such as DNA loci.★Track provides accurate predictions of particle copy number and replication timing even in the presence of substantial noise. The knowledge of these quantities are critical for uncovering the mechanisms behind many cell-cycle dependent processes, such the control of chromosome and plasmid replication initiation.
The build-up of the present-day tropical diversity of tetrapods
Authors: Quintero Ignacio , Landis Michael , Jetz Walter , Morlon Hélène
Published: December 2022

The extraordinary number of species in the tropics when compared to the extra-tropics is probably the most prominent and consistent pattern in biogeography, suggesting that overarching processes regulate this diversity gradient. A major challenge to characterizing which processes are at play relies on quantifying how the frequency and determinants of tropical and extra-tropical speciation, extinction and dispersal events shaped evolutionary radiations. We address this question by developing and applying spatio-temporal phylogenetic and paleontological models of diversification for tetrapod species incorporating paleoenvironmental variation. Our phylogenetic model results show that area, energy or species richness did not uniformly affect speciation rates across tetrapods and dispute expectations of a latitudinal gradient in speciation rates. Instead, both neontological and fossil evidence coincide in underscoring the role of extra-tropical extinctions and the outflow of tropical species in shaping biodiversity. These diversification dynamics accurately predict present-day levels of species richness across latitudes and uncover temporal idiosyncrasies but spatial generality across the major tetrapod radiations.
Validation of Fuze IMU system for ergonomics assessments
Authors: Serra-Hsu Elizabeth , Taboga Paolo
Published: December 2022

This study aims to validate the Fuze system (SwiftMotion, CA, USA), against the gold standard for motion capture, a 3D infra-red motion capture system (Vicon Nexus, Oxford, UK). Fuze system uses inertial measurement units and proprietary algorithms to calculate position and orientation of each body segment

Six subjects (3M and 3F) performed two activities that simulate common occupational physical activities. For both systems, we calculated the following joint angles: trunk relative to horizontal, left and right shoulder and hip joint angles. We also calculated the horizontal distance of each wrist relative to the the fifth lumbar vertebra. For each measurement, we calculated Bias (average difference between Fuze and Vicon system) and root mean squared error (RMSE). We also compared each measurement using a Statistical Parametric Mapping (SPM) method with a statistical significance level set at 0.05.

Compared to Vicon, Fuze system had a maximum Bias of 5.63 ± 1.60 degrees for the left shoulder angle and a maximum RMSE of 10.03 ± 2.73 degrees for the left hip angle. SPM analysis evidenced that for all the measurements, comparisons were within the critical thresholds for significance for the whole duration of the trials, indicating that we could not find a significant difference between Vicon and Fuze measurements.

In conclusion: the Fuze system compares well with the Vicon system and provides reliable data for the measurement of joint angles and body positions, that can be used in particular in non labbased settings, for example in ergonomics risk assessments.
Mapping disease regulatory circuits at cell-type resolution from single-cell multiomics data
Authors: Chen Xi , Wang Yuan , Cappuccio Antonio , Cheng Wan-Sze , Zamojski Frederique Ruf , Nair Venugopalan D. , Miller Clare M. , Rubenstein Aliza B. , Nudelman German , Tadych Alicja , Theesfeld Chandra L. , Vornholt Alexandria , George Mary-Catherine , Ruffin Felicia , Dagher Michael , Chawla Daniel G. , Soares-Schanoski Alessandra , Spurbeck Rachel R. , Ndhlovu Lishomwa C. , Sebra Robert , Kleinstein Steven H. , Letizia Andrew G. , Ramos Irene , Fowler Vance G. , Woods Christopher W. , Zaslavsky Elena , Troyanskaya Olga G. , Sealfon Stuart C.
Published: December 2022

Resolving chromatin remodeling-linked gene expression changes at cell type resolution is important for understanding disease states. We describe MAGICAL, a hierarchical Bayesian approach that leverages paired scRNA-seq and scATAC-seq data from different conditions to map disease-associated transcription factors, chromatin sites, and genes as regulatory circuits. By simultaneously modeling signal variation across cells and conditions in both omics data types, MAGICAL achieved high accuracy on circuit inference. We applied MAGICAL to studyStaphylococcus aureussepsis from peripheral blood mononuclear single-cell data that we generated from infected subjects with bloodstream infection and from uninfected controls. MAGICAL identified sepsis-associated regulatory circuits predominantly in CD14 monocytes, known to be activated by bacterial sepsis. We addressed the challenging problem of distinguishing host regulatory circuit responses to methicillin-resistant-(MRSA) and methicillin-susceptibleStaphylococcus aureus(MSSA) infections. While differential expression analysis failed to show predictive value, MAGICAL identified epigenetic circuit biomarkers that distinguished MRSA from MSSA.
Subcortical brain volumes in neonatal hypoxic-ischemic encephalopathy
Authors: Kebaya Lilian M N , Kapoor Bhavya , Mayorga Paula Camila , Meyerink Paige , Foglton Kathryn , Altamimi Talal , Nichols Emily S. , de Ribaupierre Sandrine , Bhattacharya Soume , Tristao Leandro , Jurkiewicz Michael T , Duerden Emma G.
Published: December 2022

Background

Hypoxic ischemic encephalopathy (HIE) is a severe brain injury impacting term-born neonates. Despite treatment with therapeutic hypothermia (TH), HIE is associated with myriad adverse developmental outcomes suggesting the involvement of subcortical structures, including the thalamus and basal ganglia, which may be vulnerable to perinatal asphyxia, particularly during the acute period.

Aims

1) To examine subcortical macrostructure in the first few days of life in neonates with HIE compared to age- and sex-matched healthy neonates. 2) To determine whether subcortical volumetric maturation is associated with HIE severity.

Methods

A cohort of 28 neonates (19 males [67.9%], median gestational age [GA]=38.6 weeks, interquartile range [IQR]=36.8-39.6) with HIE (mild=4, moderate=21, severe=3 based on Sarnat Staging) were scanned with MRI within the first four days of life (median postmenstrual age [PMA]=39.2, IQR=37.6-40.3), with the majority of scans occurring in the post-cooling period (n=23[82%]). The control group included 28 healthy neonates matched for GA, birth weight and PMA at the scan. Subcortical volumes (thalamus, basal ganglia, hippocampus, cerebellum) were automatically extracted from T1-weighted images. General linear models assessed between-group differences in subcortical volumes, adjusting for sex, GA, PMA, and total cerebral volumes. Within-group analyses evaluated the association between subcortical volumes and HIE severity.

Results

Neonates with HIE had significantly smaller bilateral thalamic, basal ganglia and right hippocampal and cerebellar volumes compared to healthy neonates (all, p<0.02). Within the HIE group, milder HIE severity was associated with smaller volumes of the left and right basal ganglia (both, p<0.007) and the left hippocampus and thalamus (both, p<0.04) when adjusting for TH, days of mechanical ventilation and other clinical and demographic factors.

Conclusions

Consistent with findings from childhood survivors of HIE, newborns with HIE, scanned with MRI within the first days of life, had smaller subcortical volumes impacting sensory and motor regions, including the thalamus, basal ganglia and cerebellum compared to healthy newborns. Additionally, HIE severity was associated with subcortical volumes, particularly impacting the basal ganglia, suggesting these regions may be important brain-based biomarkers in newborns impacted by the hypoxic-ischaemic injury. Findings suggest that despite advances in neonatal care, HIE is associated with significant alterations in brain macrostructure.
Production and Characterization of Monoclonal antibodies to Xenopus proteins
Authors: Horr Brett , Kurtz Ryan , Pandey Ankit , Hoffstrom Benjamin G , Schock Elizabeth , LaBonne Carole , Alfandari Dominique
Published: December 2022

Monoclonal antibodies are powerful and versatile tools that enable the study of proteins in diverse contexts. They are often utilized to assist with identifying subcellular localization and characterizing the function of target proteins of interest. However, because there can be considerable sequence diversity between orthologous proteins in Xenopus and mammals, antibodies produced against mouse or human proteins often do not recognize Xenopus counterparts. To address this issue, we refined existing protocols to produce mouse monoclonal antibodies directed against Xenopus proteins of interest. Here we describe several approaches for the generation of useful mouse anti-Xenopus antibodies to multiple Xenopus proteins and their validation in various experimental approaches. These novel antibodies are now available to the research community through theDevelopmentalStudyHybridomaBank (DSHB).

Summary statement

The manuscript describes the generation and characterization of novel monoclonal antibodies toXenopus laevisproteins using refined hybridoma production methods suitable for basic science research labs.
Genetic Mapping of Progressive Ethanol Consumption in the Diversity Outbred Mouse
Authors: Tatom Zachary , Mignogna Kristin M. , Sergi Zachary , Nguyen Jeremy , Michenkova Marie , Smith Maren L. , Miles Michael F.
Published: December 2022

Traditional genetic mapping studies using inbred crosses are a powerful tool for identifying chromosomal regions associated with ethanol-related traits, but typically have very large confidence intervals which make identification of specific and potentially causal candidate genes difficult. Diversity Outbred (DO) mice offer the ability to map quantitative trait loci (QTLs) associated with ethanol-drinking behaviors at a high resolution that allows for easier identification of candidate genes. Here, we exposed a population of 636 male DO mice to four weeks of intermittent ethanol access via a three-bottle choice paradigm, identifying 3 significant (Chrs 3, 4, and 12) and 12 suggestive loci for ethanol-drinking behaviors. The confidence intervals for these loci were narrow (1-4 Mbp for significant QTLs). We then further analyzed positional candidate genes using transcriptomics data from prefrontal cortex samples taken from 220 of these animals, as well as human GWAS data and prior gene set data for ethanol or other drugs of abuse. These results represent the highest-resolution genetic mapping of ethanol consumption behaviors in mice to date, providing for the identification of novel loci and candidate genes for progressive ethanol consumption, includingCar8--the lone gene with a significantcis-eQTL in strong linkage disequilibrium with our QTL for last week ethanol consumption on Chr 4.
Evaluation of EV Storage Buffer for Efficient Preservation of Engineered Extracellular Vesicles
Authors: Kawai-Harada Yuki , Itawi Hanine El , Komuro Hiroaki , Harada Masako
Published: December 2022

Extracellular vesicles (EVs), detectable in all bodily fluids, mediate intercellular communication by transporting molecules between cells. The capacity of EVs to transport molecules between distant organs has drawn interest for clinical applications in diagnostics and therapeutics. Although EVs hold potential for nucleic acid-based and other molecular therapeutics, the lack of standardized technologies, including isolation, characterization, and storage, leaves many challenges for clinical applications, potentially resulting in misinterpretation of crucial findings. Previously, several groups demonstrated the problems of commonly used storage methods that distort EV integrity. This work aims to evaluate the process to optimize the storage conditions of EVs and then characterize them according to the experimental conditions and the models used previously. Our study reports a highly efficient EV storage condition, focusing on EVs’ capacity to protect their molecular cargo from biological, chemical, and mechanical damage. Compared with commonly used EV storage conditions, our EV storage buffer leads to less size and particle number variation at both 4°C and -80 °C, enhancing the ability to protect EVs while maintaining targeting functionality.
Aging Fly Cell Atlas Identifies Exhaustive Aging Features at Cellular Resolution
Authors: Lu Tzu-Chiao , Brbić Maria , Park Ye-Jin , Jackson Tyler , Chen Jiaye , Kolluru Sai Saroja , Qi Yanyan , Katheder Nadja Sandra , Cai Xiaoyu Tracy , Lee Seungjae , Chen Yen- Chung , Auld Niccole , Liang Chung-Yi , Ding Sophia H. , Welsch Doug , D’Souza Samuel , Pisco Angela Oliveira , Jones Robert C. , Leskovec Jure , Lai Eric C. , Bellen Hugo J. , Luo Liqun , Jasper Heinrich , Quake Stephen R. , Li Hongjie
Published: December 2022

Aging is characterized by a decline in tissue function, but the underlying changes at cellular resolution across the organism remain unclear. Here, we present the Aging Fly Cell Atlas, a single-nucleus transcriptomic map of the whole agingDrosophila. We characterize 163 distinct cell types and perform an in-depth analysis of changes in tissue cell composition, gene expression, and cell identities. We further develop aging clock models to predict the fly age and show that ribosomal gene expression is a conserved predictive factor for age. Combining all aging features, we find unique cell type-specific aging patterns. This atlas provides a valuable resource for studying fundamental principles of aging in complex organisms.
The effectiveness of acellular nerve allografts compared to autografts in animal models: a systematic review and meta-analysis
Authors: Broeren Berend O. , Hundepool Caroline A. , Kumas Ali H. , Duraku Liron S. , Walbeehm Erik T. , Hooijmans Carlijn R. , Power Dominic M. , Zuidam J. Michiel , De Jong Tim
Published: December 2022

Background

Treatment of nerve injuries proves to be a worldwide clinical challenge. Acellular nerve allografts are suggested to be a promising alternative for bridging a nerve gap to the current gold standard, an autologous nerve graft.

Objective

To systematically review the efficacy of the acellular nerve allograft, its difference from the gold standard (the nerve autograft) and to discuss its possible indications.

Material and methods

PubMed, Embase and Web of Science were systematically searched until the 4th of January 2022. Original peer reviewed paper that presented 1) distinctive data; 2) a clear comparison between not immunologically processed acellular allografts and autologous nerve transfers; 3) was performed in laboratory animals of all species and sex. Meta analyses and subgroup analyses (for graft length and species) were conducted for muscle weight, sciatic function index, ankle angle, nerve conduction velocity, axon count diameter, tetanic contraction and amplitude using a Random effects model. Subgroup analyses were conducted on graft length and species.

Results

Fifty articles were included in this review and all were included in the meta-analyses. An acellular allograft resulted in a significantly lower muscle weight, sciatic function index, ankle angle, nerve conduction velocity, axon count and smaller diameter, tetanic contraction compared to an autologous nerve graft. No difference was found in amplitude between acellular allografts and autologous nerve transfers. Post hoc subgroup analyses of graft length showed a significant reduced muscle weight in long grafts versus small and medium length grafts. All included studies showed a large variance in methodological design.

Conclusion

Our review shows that the included studies, investigating the use of acellular allografts, showed a large variance in methodological design and are as a consequence difficult to compare. Nevertheless, our results indicate that treating a nerve gap with an allograft results in an inferior nerve recovery compared to an autograft in seven out of eight outcomes assessed in experimental animals. In addition, based on our preliminary post hoc subgroup analyses we suggest that when an allograft is being used an allograft in short and medium (0-1cm, > 1-2cm) nerve gaps is preferred over an allograft in long (> 2cm) nerve gaps.
Pynapple, a toolbox for data analysis in neuroscience
Authors: Viejo Guillaume , Levenstein Daniel , Carrasco Sofia Skromne , Mehrotra Dhruv , Mahallati Sara , Vite Gilberto R , Denny Henry , Sjulson Lucas , Battaglia Francesco P , Peyrache Adrien
Published: December 2022

Datasets collected in neuroscientific studies are of ever-growing complexity, often combining high dimensional time series data from multiple data acquisition modalities. Handling and manipulating these various data streams in an adequate programming environment is crucial to ensure reliable analysis, and to facilitate sharing of reproducible analysis pipelines. Here, we present Pynapple, the PYthon Neural Analysis Package, a lightweight python package designed to process a broad range of time-resolved data in systems neuroscience. The core feature of this package is a small number of versatile objects that support the manipulation of any data streams and task parameters. The package includes a set of methods to read common data formats and allows users to easily write their own. The resulting code is easy to read and write, avoids low-level data processing and other error-prone steps, and is open source. Libraries for higher-level analyses are developed within the Pynapple framework but are contained within in a collaborative repository of specialized and continuously updated analysis routines. This provides flexibility while ensuring long-term stability of the core package. In conclusion, Pynapple provides a common framework for data analysis in neuroscience.

Highlights

An open-source framework for data analysis in systems neuroscience.

Easy-to-use object-oriented programming for data manipulation.

A lightweight and standalone package ensuring long-term backward compatibility.