bluuebunny/crossref_metadata_2025 huggingface dataset:
What is Back Pain?
Authors: Lee John , Brook Suzanne , Daniel Clare
Published: November 2023

The question ̒what is back pain?̓ is understandable but the answer can be complicated. This chapter discusses: why people feel pain at all the difference between acute and long-term pain how the body repairs itself how pathways can develop that promote long-term back pain. It also describes the defi nitions of pain used both in everyday life and in scientific literature which demonstrate how pain affects us in so many different ways. Understanding the origins of a problem usually go a long way to managing them better.
Can My Back Pain be Cured by Injections or Surgery?
Authors: Lee John , Brook Suzanne , Daniel Clare
Published: November 2023

There are many treatments offered to patients with back pain by way of ̒interventions̓ using injections, implantable devices or surgery. Some of these will be smaller undertakings (such as injections) and others may be much larger where you should anticipate an extended period of recovery (such as surgery). There are also different types of practitioners that might offer things. Interventional techniques depend on the training of the individual providing them and this varies from one practitioner to the next. Table 6.1 is a generalized list of these practitioners and the services they offer.
Specific Stretches and Exercises
Authors: Lee John , Brook Suzanne , Daniel Clare
Published: November 2023

Warm-up exercises are just what they say—to warm up your muscles and joints in preparation for more stretches, exercise or activity. Warm-up exercises do not take long, and can be squeezed into any free minute. They can be done at any time and anywhere, and can be especially useful if you have been still in one position for a while, for example sitting in a car, in a queue or in the cinema.
Making Sense of Scan Results and Finding a Cure
Authors: Lee John , Brook Suzanne , Daniel Clare
Published: November 2023

Mr Webb is 56 years old. His back pain began for no apparent reason three years ago. He has seen a rheumatologist, spinal surgeon, neurologist, and pain management consultant. They have all sent him for investigations, such as blood tests, X-rays, and MRI scans but all the reports were normal and he has been told that nothing can be found that is causing his pain. Mr Webb thinks that people think that the pain is all in his mind. He has seen the results of his MRI scan and he is sure that the discs in his back are damaged and causing his pain.
Russian Law
Authors: Butler William E
Published: November 2023

When the first edition of Professor Butler's book was published in 1999 it was hailed as the first systematic account of Russian law and the Russian legal system since the demise of the Soviet Union. The second edition built on his examination of Russian law in the context of other legal systems and made a thorough examination of the country's legal institutions and procedural and substantive law. In this third edition the author reviews the law reform of Putin's era, including the impact of decisions of the European Court of Human Rights as sources of Russian Law, a new chapter on insurance law and the essentials of local government law. The book has been updated throughout to include the latest legislation since the last edition, including reform of the law of intellectual property, competition, foreign investment, the legal status of foreigners, treaties, securities, pledge and mortgage, State corporations, the legal profession and the penal system, labour law, taxation, procedure, international arbitration, the judicial system and procuracy, justices of the peace, State structure, and environmental and natural resource law . Butler's emphasis is on post-Soviet law reform and on the creation of a democratic, market-oriented legal framework which seeks to attract foreign investment. Chapters such as those on entrepreneurial law, securities regulation, banking and insurance, taxation, and the status of foreigners and foreign investment law make this volume an essential purchase for those advising potential investors in Russia and the CIS. For those with a more academic interest in Russian law there are also chapters on Russian legal history and legal theory, together with a detailed guide to relevant publications and materials. This authoritative work will be embraced by practising lawyers, the investment community, government legal advisors, and scholars seeking a comprehensive and practical introduction to the Russian legal system.
How the normal lungs work
Authors: Currie Graeme P
Published: November 2023

Air containing oxygen passes through the mouth and nose into the windpipe (trachea). The windpipe then divides repeatedly into smaller branches of increasingly narrow size (bronchi and bronchioles) within the lungs. The smallest air passages (bronchioles) end as tiny air sacs (alveoli) where gas exchange takes place; oxygen passes from the air sacs into the blood and carbon dioxide passes from the blood into the air sacs.
Managing COPD without drugs
Authors: Currie Graeme P
Published: November 2023

Non-drug treatment plays a vital role in the management of COPD. A variety of health care professionals may offer different forms of help in the management of COPD. Examples of non-drug treatment include education, pulmonary rehabilitation, vaccination, encouragement of exercise, and dietary advice. Anxiety and depression are common in COPD; all doctors and nurses should look for them and treat accordingly.
Recovery
Authors: Bocco Riccardo , Harrisson, Pierre , Oesch Lucas
Published: November 2023

Into the 1990s, the ‘relief and development continuum’ approach led mainstream discourses and practices in the international community related to post-crisis interventions. This concept was based on the understanding that relief and development should follow a logical and linear sequence of phases, where different types of interventions follow each other successively. Since the early 1990s, however, inspired by experiences of international agencies in the field, considerations about the need to integrate relief and development, and not merely to coordinate the two, have emerged in parallel. Since 2005, these concepts have started to crystallize within the UN system into what can be called the ‘recovery approach’.
Intelligent Research Design
Authors: Hancké Bob
Published: November 2023

This book offers advice to doctoral researchers and graduate and advanced undergraduate students on how to embark on their research. Based on a decade of teaching early-stage researchers in the social sciences at the LSE and other universities, and written with the central problems of beginning researchers in mind, Bob Hancké guides them through the process of thinking about the links between theory, cases and data, and to do so in a way that helps to turn their initial plausible ideas into convincing arguments. This lively book, deliberately jargon-free and with a hands-on, pragmatic approach to research design, addresses the problems that research students face - or ignore, often at their peril - in the course of their first few years. Its central message is that research is a complex and iterative process in which researchers construct every relevant part of their project with one goal in mind: make a persuasive point. They define the question they ask and the debate they engage, construct their cases and data to answer that question, and write it up as an argument that brings out the strengths of their research design. It addresses such key issues as statistical versus configurational approaches, time in social science research, different types of case studies and comparative research, and a critical approach to data. The Appendix gives tips on presenting and discussing papers, and on crafting research proposals.
Constructing Data
Authors: Hancké Bob
Published: November 2023

‘When I was interviewing the head of the nationalist party, Mr Smith, he told me that I was right: his political party did X because of Y, just as I had predicted, so I wrote it in my dissertation. During the defence, however, one of the readers asked me if there was any corroborating evidence to that statement which was available to the readers of the thesis, and I told him I did not need that, since the guy who was in charge of the political party had actually told me what they had done and why. They sent me off with the message to use the next year to think about how to make that claim stick. What more did these guys want from me? I got it from the horse’s mouth!’ The thesis jury in this imaginary chat in the pub may have looked unfair to John, but they had a more than reasonable point: Smith may or may not have told the truth—and there is no a priori reason to assume he had not—but that was not good enough for them. They were asking John to show them that what he discovered during that interview was good enough to hang a whole thesis on, since in the way John had presented his material, it failed to meet the basic criteria that would allow them to conclude that. Fortunately, what happened to John is rare—though far from non-existent. We all have an intuition about what went wrong in John’s thesis defence, and by making explicit what went wrong, this chapter offers a tool kit to help you avoid making those mistakes in your own work.
Prologue
Authors: Sachs Justice Albie
Published: November 2023

Life prepared me in a most bizarre way for becoming a judge. If judicial office had been my goal I was doing everything right . . . eight years of study and three degrees including a doctorate in law, a decade of busy practice as an advocate at the Cape Town Bar, and, later, earnestly teaching law in three continents and publishing several books, some scholarly, others autobiographical. Yet as far as the actual impact of the law on my life was concerned, everything was wrong: as a student my home was raided before dawn by the police and I was subjected to what was called a ‘banning order’ that restricted my movements and activities; while at the Bar I was twice placed in solitary confinement by the security police, first for 168 days and later for 3 months, during which I suffered torture by sleep deprivation; when I completed my doctorate I was living as a stateless person in exile in England; and some years later while doing legal research in Mozambique I was blown up by a bomb placed in my car by my country’s security agents, losing an arm and the sight of an eye.
Protein-Protein Recognition
Authors: Kleanthous Colin
Published: November 2023

The purpose of Protein-Protein Recognition is to bring together concepts and systems pertaining to protein-protein interactions in a single unifying volume. In the light of the information from the genome sequencing projects and the increase in structural information it is an opportune time to try to make generalizations about how and why proteins form complexes with each other. The emphasis of the book is on heteromeric complexes (complexes in which each of the components can exist in an unbound state) and will use well-studied model systems to explain the processes of forming complexes. After an introductory section on the kinetics, thermodynamics, analysis, and classification of protein-protein interactions, weak, intermediate, and high affinity complexes are dealt with in turn. Weak affinity complexes are represented by electron transfer proteins and integrin complexes. Anti-lysozyme antibodies, the MHC proteins and their interactions with T-cell receptors, and the protein interactions of eukaryotic signal transduction are the systems used to explain complexes with intermediate affinities. Finally, tight binding complexes are represented by the interaction of protein inhibitors with serine proteases and by nuclease inhibitor complexes. Throughout the chapters common themes are the technologies which have had the greatest impact, how specificity is determined, how complexes are stabilized, and medical and industrial applications.
Association of Patient Race and Hospital with Utilization of Regional Anesthesia for Treatment of Postoperative Pain in Total Knee Arthroplasty: A Retrospective Analysis Using Medicare Claims
Authors: Dixit Anjali A. , Sekeres Gabriel , Mariano Edward R. , Memtsoudis Stavros G. , Sun Eric C.
Published: November 2023

Background

Regional anesthesia for total knee arthroplasty has been deemed high priority by national and international societies, and its use can serve as a measure of healthcare equity. The association between utilization of regional anesthesia for postoperative pain and (1) race and (2) hospital in patients undergoing total knee arthroplasty was estimated. The hypothesis was that Black patients would be less likely than White patients to receive regional anesthesia, and that variability in regional anesthesia would more likely be attributable to the hospital where surgery occurred than race.

Methods

This study used Medicare fee-for-service claims for patients aged 65 yr or older who underwent primary total knee arthroplasty between January 1, 2011, and December 31, 2016. The primary outcome was administration of regional anesthesia for postoperative pain, defined as any peripheral (femoral, lumbar plexus, or other) or neuraxial (spinal or epidural) block. The primary exposure was self-reported race (Black, White, or Other). Clinical significance was defined as a relative difference of 10% in regional anesthesia administration.

Results

Data from 733,406 cases across 2,507 hospitals were analyzed: 90.7% of patients were identified as White, 4.7% as Black, and 4.6% as Other. Median hospital-level prevalence of use of regional anesthesia was 51% (interquartile range, 18 to 79%). Black patients did not have a statistically different probability of receiving a regional anesthetic compared to White patients (adjusted estimates: Black, 53.3% [95% CI, 52.5 to 54.1%]; White, 52.7% [95% CI, 52.4 to 54.1%]; P = 0.132). Findings were robust to alternate specifications of the exposure and outcome. Analysis of variance revealed that 42.0% of the variation in block administration was attributable to hospital, compared to less than 0.01% to race, after adjusting for other patient-level confounders.

Conclusions

Race was not associated with administration of regional anesthesia in Medicare patients undergoing primary total knee arthroplasty. Variation in the use of regional anesthesia was primarily associated with the hospital where surgery occurred.

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What We Already Know about This Topic

What This Article Tells Us That Is New
5-Aminolevulonic Acid, a New Tumor Contrast Agent: Anesthesia Considerations in Patients Undergoing Craniotomy
Authors: Schusteff Rachel A. , Slavin Konstantin V. , Roth Steven
Published: November 2023

5-aminolevulinic acid (ALA) is used during resection of malignant gliomas due to its fluorescence properties and has been shown to render resection more effective than resection without ALA guidance. The aim of this narrative review is to categorize the adverse effects of ALA relevant to anesthesia providers. Intraoperative hypotension, porphyria-related side effects, alterations in blood chemistry and coagulation, photosensitivity, and increased levels of liver enzymes have all been reported. We also sought to examine the impact of dosage and timing of oral administration on efficacy of ALA and on these side effects. Twenty-seven studies met our inclusion criteria of patients undergoing craniotomy for glioma resection using ALA and occurrence of at least one adverse effect. The results of these studies showed that there was heterogeneity in levels of intraoperative hypotension, with some reporting an incidence as high as 32%, and that hypotension was associated with antihypertensive medication use. Clinical symptoms of porphyria, such as gastrointestinal disturbance, were less commonly reported. Photosensitivity of the skin after 5-ALA administration was well documented particularly in patients exposed to light; however, adverse effects on the eye were not adequately studied. Elevation in liver enzymes was a common finding postoperatively but was often clinically insignificant. The timing of oral administration presents practical issues for the preoperative management of patients undergoing resection with ALA. We provide guidance for perioperative management of patients who receive ALA for brain tumor resection. Controlled studies with adequate statistical power are required to further understand and prevent the adverse effects of ALA.
Ultrasound evaluation of the femoral trochlea in newborns: incidence of trochlear dysplasia and associated risk factors
Authors: Masquijo Javier , Bruno Angeles , Warde Agustina , Mónico Carola , Turazza Florencia
Published: November 2023

This study aimed to describe the femoral groove morphology using ultrasound in children under 6 months, estimate the incidence of trochlear dysplasia, and evaluate associated risk factors. A prospective study included 298 patients who underwent universal ultrasound screening for hip dysplasia [developmental dysplasia of the hip (DDH)] and knee ultrasound. Measurements of sulcus angle (SA), trochlear depth (TD), and trochlear facet asymmetry (TFA) were analyzed. Trochlear dysplasia was considered present if the ASO was ≥159°. Reproducibility was assessed using the intraclass correlation coefficient (ICC) in 60 knees. Logistic regression adjusted for confounders, presenting odds ratios (OR) and 95% confidence intervals (CI). Significance was set at P < 0.05. Analysis included 596 knees (298 patients). Females accounted for 51% of patients, with 7% having breech presentation, 4.4% DDH, 6.4% family history of DDH, and 5% family history of patellofemoral instability. ICC showed excellent agreement for SA and TD, but poor for TFA. Trochlear dysplasia incidence was 3% (9/298; 67% bilateral). Median (IQR) values were 147.5 (144.0–150.5) for SA, 2.4 (2.2–2.8) for TD, and 1.1 (1.0, 1.1) for TFA. Breech presentation (OR, 9.68; 95% CI 1.92–48.71, P = 0.006) and concomitant DDH (OR 6.29, 95% CI 1.04–37.78, P = 0.044) were associated with trochlear dysplasia. Ultrasound effectively evaluates femoral groove morphology and diagnoses trochlear dysplasia in newborns. Trochlear dysplasia incidence was 3%, with a 10-fold higher risk in breech presentation and 6-fold higher risk in concomitant DDH. Standardized screening and timely treatment protocols should be further investigated. Level of evidence: Diagnostic Level II.
The Roles of Venopulmonary Arterial Extracorporeal Membrane Oxygenation
Authors: Hockstein Maxwell A. , Fan Eddy
Published: November 2023

OBJECTIVES:

Concise definitive review of the use of venopulmonary arterial extracorporeal membrane oxygenation (V-PA ECMO) support in patients with cardiopulmonary failure.

DATA SOURCES:

Original investigations identified through a PubMed search with search terms “percutaneous right ventricular assist device,” “oxy-RVAD,” “V-PA ECMO,” and “veno-pulmonary arterial ECMO” were reviewed and evaluated for relevance.

STUDY SELECTION:

Studies that included more than three patients supported with V-PA ECMO were included.

DATA EXTRACTION:

Clinically relevant data from included studies, including patient-important outcomes, were summarized and discussed.

DATA SYNTHESIS:

We identified four groups of patients where V-PA ECMO has been studied: acute respiratory distress syndrome, right ventricular dysfunction after left ventricular assist device placement, bridge to lung transplantation, and pulmonary embolism. Most identified works are small, single center, and retrospective in nature, precluding definitive conclusions regarding the efficacy of V-PA ECMO. There have been no clinical trials evaluating the efficacy of V-PA ECMO for any indication.

CONCLUSIONS:

V-PA ECMO is a promising form of extracorporeal support for patients with right ventricular dysfunction. Future work should focus on identifying the optimal timing and populations for the use of V-PA ECMO.
Pharmacogenetics of weight gain following switch from efavirenz- to integrase inhibitor-containing regimens
Authors: Wu Kunling , Koethe John , Hulgan Todd , Brown Todd , Bares Sara H. , Tassiopoulos Katherine , Lake Jordan E. , Leonard Michael , Samuels David C. , Erlandson Kristine , Haas David W.
Published: November 2023

Background

Excessive weight gain affects some persons with HIV after switching to integrase strand transfer inhibitor (INSTI)-containing antiretroviral therapy (ART). We studied associations between CYP2B6 genotype and weight gain after ART switch among ACTG A5001 and A5322 participants.

Methods

Eligible participants switched from efavirenz- to INSTI-containing ART, had genotype data, and had weight data at least once from 4 weeks to 2 years post-switch. Multivariable linear mixed effects models adjusted for race/ethnicity, CD4, age, BMI and INSTI type assessed relationships between CYP2B6 genotype and estimated differences in weight change.

Results

A total of 159 eligible participants switched ART from 2007 to 2019, of whom 138 had plasma HIV-1 RNA < 200 copies/mL (65 CYP2B6 normal, 56 intermediate, 17 poor metabolizers). Among participants with switch HIV-1 RNA < 200 copies/mL, weight increased in all 3 CYP2B6 groups. The rate of weight gain was greater in CYP2B6 poor than in CYP2B6 normal metabolizers overall, and within 9 subgroups (male, female, White, Black, Hispanic, dolutegravir, elvitegravir, raltegravir, and TDF in the pre-switch regimen); only in Hispanic and elvitegravir subgroups were these associations statistically significant (P < 0.05). Compared to normal metabolizers, CYP2B6 intermediate status was not consistently associated with weight gain.

Conclusion

CYP2B6 poor metabolizer genotype was associated with greater weight gain after switch from efavirenz- to INSTI-containing ART, but results were inconsistent. Weight gain in this setting is likely complex and multifactorial.
Utility of Respiratory Pathogen Panels in the Outpatient Oncology Setting
Authors: Gripp Emily W. , Hess Bryan D. , Binder Adam F.
Published: November 2023

Oncology patients presenting for outpatient evaluation of a respiratory tract infection (RTI) are often tested for a variety of viruses with a respiratory pathogen panel (RPP) in addition to influenza and SARS-CoV-2. This triad of testing is expensive and uncomfortable because it requires 2 nasal swabs. Little evidence supports the use of an RPP in outpatient settings, but it is routinely ordered. This retrospective chart review analyzed 183 RPPs performed at Jefferson between April 2020 and November 2021 in outpatient oncology patients presenting with RTI. Data collected included patient demographics, symptoms, and exam findings at time of RPP, additional testing completed, results of RPP, antibiotic and antiviral use before and after RPP results, and patient outcomes 30 days after RPP. Descriptive statistics were calculated. Of the 183 RPPs analyzed, 16.9% (31) were positive for at least 1 respiratory virus. Fifty-two patients (28.4%) started antibiotics before results of the RPP. Of those, 2 patients (3.8%) had a change in antibiotic plan after RPP results returned. Zero patients were started on antiviral medication before results of the RPP. One patient started antiviral treatment after RPP results returned. In total, only 3 patients (1.6%) had an RPP-driven change in medication management. This study suggests limited utility in use of RPPs for oncology patients presenting to the office with RTI symptoms. Targeted testing with a single nasal swab for influenza, RSV, and SARS-CoV-2 may be more clinically relevant. The authors hope to use these data to implement a quality improvement initiative to reduce RPP utilization in this population.
Racial disparities in the treatment of pancreatic cancer: results from the analysis of a National Database
Authors: Onyemkpa Chibueze , Dougherty Danielle , Samat Sajjaad , Oyasiji Tolutope , McLeod Michael
Published: November 2023

Background:

Pancreatic cancer is the third leading cause of cancer death in the US. There have been postulates of racial disparities. Based on this, we primarily examined the presence of race, for the diagnosis and treatment of pancreatic cancer.

Methods:

A retrospective review was conducted on patients with pancreatic cancers using the Surveillance Epidemiology, and End Results - Medicare registry. Univariate and multivariate analyses were performed. Overall Survival analysis was done using the Kaplan-Meier curve. Comparison of survival curves was done using the log-rank test. Cox proportional hazards regression model was used to determine independent predictors of survival. Other areas focused on were time interval from diagnosis to treatment, “Predictors of surgery of the primary site,” “Predictors for recommending surgery of the primary site,” “Predictors for oncologic resection,” “Predictors of performance and refusal of surgery of primary site if recommended,” and “Predictors for any other therapy (all therapies excluding surgery).

Results:

A total of 52,951 patients were identified from the database. A total of 24,523 were males and 26,715 were females. A total of 81.9% were Caucasian, 10.9% were Black, and 7.2% were other races. There was approximately equal distribution of the different stages between both genders. A total of 10.2% of the females were diagnosed at stage I, 28.9%, 9.3%, and 51.6% at stages I, III, and IV, respectively, compared to males with 8.4%, 28.3%, 9.2%, and 54.1% for stages I, II, III, and IV, respectively. A total of 9.5% of the Black patients were diagnosed at stage I, 24.2% at stage II, 10.1% at stage III, and 56.2% at stage IV. A similar distribution was noted in the other races. Black patients had worse overall survival when compared to Caucasians (P = .004) and other races (P = .001).

Conclusion:

Compared to Caucasian patients, Black patients with pancreatic cancer had worse overall survival.
Assessment of frequency and types of drug interactions in intensive care units: a cross-sectional study
Authors: Baghaei Rahim , Torabzadeh Aysan , Sorayya Hamid , Alinejad Vahid
Published: November 2023

Background:

Drug interactions can cause adverse reactions, from treatment inefficiency to serious treatment complications in the patient. Due to the complexity of drug therapy and the simultaneous use of several drugs and different drug groups, patients hospitalized in intensive care units are exposed to more drug interactions. Therefore, this study was conducted to investigate the frequency of drug interactions in patients hospitalized in the ICU.

Methods:

In this cross-sectional study, the files of 300 patients hospitalized in the ICU were examined. Drug interactions were determined using Lexicomp software and the book drug iteration facts. Data analysis was done using SPSS 21 software.

Findings:

The findings showed that there were a total of 1121 cases of interference. Two hundred thirty-one (77%) patients had moderate interference, 94 (31.3%) patients had mild interference, and 67 patients (22.3%) had severe interference. One hundred eight patients had B-type interference, 223 C-type interference, 116 D-type interference, and 6 X-type interference, so most of the interactions are C-type interference. One hundred eighty-six patients had pharmacokinetic interference and 201 patients had pharmacodynamics interference. The highest interaction was between two drugs, heparin and aspirin with 58 cases.

Conclusion:

This study highlights the alarming frequency and types of drug interactions observed in ICU. The high prevalence of drug interactions emphasizes the need for improved medication management and vigilance in these critical care settings. Polypharmacy and certain drug combinations were identified as major contributing factors to the occurrence of drug interactions, which calls for regular medication reviews and cautious prescribing practices.
The first European woolly rhinoceros mitogenomes, retrieved from cave hyena coprolites, suggest long-term phylogeographic differentiation
Authors: Seeber P. A. , Palmer Z. , Schmidt A. , Chagas A. , Kitagawa K. , Marinova-Wolff E. , Tafelmaier Y. , Epp L. S.
Published: November 2023

The woolly rhinoceros (
Coelodonta antiquitatis
) is an iconic species of the Eurasian Pleistocene megafauna, which was abundant in Eurasia in the Pleistocene until its demise beginning approximately 10 000 years ago. Despite the early recovery of several specimens from well-known European archaeological sites, including its type specimen (Blumenbach 1799), no genomes of European populations were available so far, and all available genomic data originated exclusively from Siberian populations. Using coprolites of cave hyenas (
Crocuta crocuta spelea
) recovered from Middle Palaeolithic layers of two caves in Germany (Bockstein-Loch and Hohlenstein-Stadel), we isolated and enriched predator and prey DNA to assemble the first European woolly rhinoceros mitogenomes, in addition to cave hyena mitogenomes. Both coprolite samples produced copious sequences assigned to
C. crocuta
(27% and 59% mitogenome coverage, respectively) and woolly rhinoceros (
Coelodonta antiquitatis
; 27% and 81% coverage, respectively). The sequences suggested considerable DNA degradation, which may limit the conclusions to be drawn; however, the mitogenomes of European woolly rhinoceros are genetically distinct from the Siberian woolly rhinoceros, and analyses of the more complete mitogenome suggest a split of the populations potentially coinciding with the earliest fossil records of woolly rhinoceros in Europe.
Quantifying the large-scale chromosome structural dynamics during the mitosis-to-G1 phase transition of cell cycle
Authors: Chu Xiakun , Wang Jin
Published: November 2023

Cell cycle is known to be regulated by the underlying gene network. Chromosomes, which serve as the scaffold for gene expressions, undergo significant structural reorganizations during mitosis. Understanding the mechanism of the cell cycle from the chromosome structural perspective remains a grand challenge. In this study, we applied an integrated theoretical approach to investigate large-scale chromosome structural dynamics during the mitosis-to-G1 phase transition. We observed that the chromosome structural expansion and adaptation of the structural asphericity do not occur synchronously and attributed this behaviour to the unique unloading sequence of the two types of condensins. Furthermore, we observed that the coherent motions between the chromosomal loci are primarily enhanced within the topologically associating domains (TADs) as cells progress to the G1 phase, suggesting that TADs can be considered as both structural and dynamical units for organizing the three-dimensional chromosome. Our analysis also reveals that the quantified pathways of chromosome structural reorganization during the mitosis-to-G1 phase transition exhibit high stochasticity at the single-cell level and show nonlinear behaviours in changing TADs and contacts formed at the long-range regions. Our findings offer valuable insights into large-scale chromosome structural dynamics after mitosis.
Dynamical methods for target control of biological networks
Authors: Parmer Thomas , Radicchi Filippo
Published: November 2023

Estimating the influence that individual nodes have on one another in a Boolean network is essential to predict and control the system’s dynamical behaviour, for example, detecting key therapeutic targets to control pathways in models of biological signalling and regulation. Exact estimation is generally not possible due to the fact that the number of configurations that must be considered grows exponentially with the system size. However, approximate, scalable methods exist in the literature. These methods can be divided into two main classes: (i) graph-theoretic methods that rely on representations of Boolean dynamics into static graphs and (ii) mean-field approaches that describe average trajectories of the system but neglect dynamical correlations. Here, we compare systematically the performance of these state-of-the-art methods on a large collection of real-world gene regulatory networks. We find comparable performance across methods. All methods underestimate the ground truth, with mean-field approaches having a better recall but a worse precision than graph-theoretic methods. Computationally speaking, graph-theoretic methods are faster than mean-field ones in sparse networks, but are slower in dense networks. The preference of which method to use, therefore, depends on a network’s connectivity and the relative importance of recall versus precision for the specific application at hand.
Naming the menagerie: creativity, culture and consequences in the formation of scientific names
Authors: Heard Stephen B. , Mlynarek Julia J.
Published: November 2023

The coining of scientific names for newly described species is one of the most creative acts in science. We briefly review the history of species naming, with an emphasis on constraints and freedoms in the choice of new names and how they came to be. We then consider patterns in etymologies and linguistic origins of scientific names across clades and through time. Use of ‘non-classical’ languages (those other than Latin and Greek) in naming species has increased, as has the use of eponymous names (despite recent controversy around the practice). Finally, we consider ways in which creativity in naming has consequences for the conduct and outcome of scientific work. For example, sale of naming rights has funded research and conservation, while naming species after celebrities has increased media attention to the science of species discovery. Other consequences of naming are more surprising, including a strong effect of species-name etymology on the kinds of scientific studies conducted for plant-feeding arthropods. Scientific naming is a clear example of how science and scientists are socially situated, and how culturally influenced decisions such as what to name a new species can affect both public perception of science and the conduct of science itself.
Estimating prevalence of Enterovirus D111 in human and non-human primate populations using cross-sectional serology
Authors: Kamau Everlyn , Bessaud Mael , Majumdar Manasi , Martin Javier , Simmonds Peter , Harvala Heli
Published: November 2023

Enteroviruses primarily affect young children with a varying severity of disease. Recent outbreaks of severe respiratory and neurological disease due to EV-D68 and EV-A71, as well as atypical hand-foot-and-mouth-disease due to CVA6, have brought to light the potency of enteroviruses to emerge as severe human pathogens. Enterovirus D111 (EV-D111) is an enteric pathogen initially detected in Central Africa in human and wildlife samples and was recently detected in environmental samples. The natural history and epidemiology of EV-D111 are poorly studied. Here, the presence of serum neutralizing antibodies to EV-D111 was estimated in human and wildlife samples from five countries. We report high prevalence of neutralizing antibodies measured against EV-D111 in human populations (range, 55–83 %), a proxy for previous infection, which indicates active virus circulation in absence of detection in clinical cases and a high number of undiagnosed infections. Notably, seroprevalence in samples from the UK varied by age and was higher in children and older adults (1–5 and >60 years old), but lower in ages 11–60. EV-D111 seroprevalence in apes and Old World monkeys was 50 % (33–66 %), which also suggests prior exposure and supports existing knowledge of enterovirus circulation in wild and captive apes and Old World monkeys. Generally, reported cases of infection likely underestimate the prevalence of infection particularly when the knowledge of community transmission is limited. Continued serologic surveillance and detection of EV-D111 in clinical and environmental samples will allow for a more robust assessment of EV-D111 epidemiology.
Capillary regression leads to sustained local hypoperfusion by inducing constriction of upstream transitional vessels
Authors: Bonney Stephanie K. , Nielson Cara D. , Sosa Maria J. , Shih Andy Y.
Published: November 2023

In the brain, a microvascular sensory web coordinates oxygen delivery to regions of neuronal activity. This involves a dense network of capillaries that send conductive signals upstream to feeding arterioles to promote vasodilation and blood flow. Although this process is critical to the metabolic supply of healthy brain tissue, it may also be a point of vulnerability in disease. Deterioration of capillary networks is a hallmark of many neurological disorders and how this web is engaged during vascular damage remains unknown. We performedin vivotwo-photon microscopy on young adult mural cell reporter mice and induced focal capillary injuries using precise two-photon laser irradiation of single capillaries. We found that ∼63% of the injuries resulted in regression of the capillary segment 7-14 days following injury, and the remaining repaired to re-establish blood flow within 7 days. Injuries that resulted in capillary regression induced sustained vasoconstriction in the upstream arteriole-capillary transition (ACT) zone at least 21 days post-injury in both awake and anesthetized mice. This abnormal vasoconstriction involved attenuation of vasomotor dynamics and uncoupling from mural cell calcium signaling following capillary regression. Consequently, blood flow was reduced in the ACT zone and in secondary, uninjured downstream capillaries. These findings demonstrate how capillary injury and regression, as often seen in age-related neurological disease, can impair the microvascular sensory web and contribute to cerebral hypoperfusion.

SIGNIFICANCE

Deterioration of the capillary network is a characteristic of many neurological diseases and can exacerbate neuronal dysfunction and degeneration due to poor blood perfusion. Here we show that focal capillary injuries can induce vessel regression and elicit sustained vasoconstriction in upstream transitional vessels that branch from cortical penetrating arterioles. This reduces blood flow to broader, uninjured regions of the same microvascular network. These findings suggest that widespread and cumulative damage to brain capillaries in neurological disease may broadly affect blood supply and contribute to hypoperfusion through their remote actions.
Prediction of donor heart acceptance for transplant and its clinical implications – results from the Donor Heart Study
Authors: Wayda Brian , Weng Yingjie , Zhang Shiqi , Luikart Helen , Pearson Thomas , Wood R. Patrick , Nieto Javier , Nicely Bruce , Geraghty PJ , Belcher John , Nguyen John , Neidlinger Nikole , Groat Tahnee , Malinoski Darren , Zaroff Jonathan , Khush Kiran K.
Published: November 2023

Background

Despite a shortage of potential donors for heart transplant in the United States (US), most potential donor hearts are discarded. We evaluated predictors of donor heart acceptance in the US and applied modern analytic methods to improve prediction.

Methods

We included anationwide(2005 – 2020) cohort of potential heart donors in the US (n = 73,948) from the Scientific Registry of Transplant Recipients and a more recent (2015 – 2020) rigorously phenotyped cohort of potential donors from the Donor Heart Study (DHS; n = 4,130). We identified predictors of acceptance for heart transplant in both cohorts using multivariate logistic regression, incorporating time-interaction terms to characterize their varying effects over time. We fit models predicting acceptance for transplant in a 50% training subset of the DHS using multiple machine learning algorithms and compared their performance in the remaining 50% (test) subset.

Results

Predictors of donor heart acceptance were similar in thenationwideandDHScohorts. Among these, older age has become increasingly predictive of discard over time while other factors – including those related to drug use, infection, and mild cardiac diagnostic abnormalities - have become less influential. A random forest model (area under the curve 0.90, accuracy 0.82) outperformed other prediction algorithms in the test subset and was used as the basis of a novel web-based prediction tool.

Conclusions

Predictors of donor heart acceptance for transplantation have changed significantly over the last two decades, likely reflecting evolving evidence regarding their impact on post-transplant outcomes. Real-time prediction of donor heart acceptance, using our web-based tool, may improve efficiency during donor management and heart allocation.

Clinical Perspective

Predictors of donor heart acceptance for transplantation have changed significantly over the last two decades. Donor age has become increasingly influential while several other factors have become less so - likely reflecting the lack of evidence regarding their impact on post-transplant outcomes. Our web-based tool can enable real-time prediction of donor heart acceptance, and thereby improve efficiency during donor management and heart allocation.
Distinct pathway-based effects of blood pressure and body mass index on cardiovascular traits: comparison of novel Mendelian Randomization approaches
Authors: Sobczyk Maria K , Richardson Tom G , Leyden Genevieve M , Gaunt Tom R
Published: November 2023

Background

Mendelian randomization (MR) leverages genetic variants as instrumental variables to determine causal relationships in epidemiology. However, challenges persist due to heterogeneity arising from horizontal pleiotropy. On the other hand, exploration of the biological underpinnings of such heterogeneity across variants can enhance our understanding of disease mechanisms and inform therapeutic strategies. Here, we introduce a new approach to instrument partitioning based on enrichment of Mendelian disease categories and compare it to a method based on genetic colocalisation in contrasting tissues.

Methods

We employed one-sample and two-sample MR methodologies using blood pressure (BP) exposure SNPs grouped by proximity to Mendelian disease genes affecting the renal system or vasculature, or body mass index (BMI) variants related to mental health and metabolic Mendelian disorders. We then compared the causal effects of Mendelian-partitioned SNPs on cardiometabolic outcomes with subsets inferred from gene expression colocalisation in kidney, artery (for BP), adipose, and brain tissues (for BMI). Additionally, we assessed whether effects from these groupings could emerge by chance using random SNP subset sampling.

Results

Our findings suggest that the causal relationship between systolic BP and coronary heart disease is predominantly driven by SNPs associated with vessel- related Mendelian diseases over renal. However, kidney-oriented SNPs showed more pronounced effect size in the colocalization-based analysis, hinting at a multifaceted interplay between pathways in the disease aetiology. We consistently identified a dominant role of Mendelian vessel and coloc artery exposures in driving the negative effect of diastolic BP on left ventricular stroke volume and positive effect of systolic BP on type 2 diabetes. We also found higher causal estimates for metabolic versus mental health SNPs when dissecting BMI pathway contribution to atrial fibrillation risk using Mendelian disease. In contrast, brain variants yielded higher causal estimates than adipose in the colocalization method.

Conclusions

This study presents a novel approach to dissecting heterogeneity in MR by integrating clinical phenotypes associated with Mendelian disease. Our findings emphasize the importance of understanding tissue-/pathway- specific contributions in interpreting causal relationships in MR. Importantly, we advocate caution in interpreting pathway-partitioned effect size differences without robust statistical validation.
The implications of using maternity care deserts to measure progress in access to obstetric care: A mixed-integer optimization analysis
Authors: Meredith Meghan E. , Steimle Lauren N. , Radke Stephanie M.
Published: November 2023

Background

Lack of access to risk-appropriate maternity services, particularly for rural residents, is thought to be a leading contributor to disparities in maternal morbidity and mortality. There are several existing measures of access to obstetric care in the literature and popular media. In this study, we explored how current measures of obstetric access inform the number and location of additional obstetric care facilities required to improve access.

Methods

We formulated two facility location optimization models to determine the number of new facilities required to minimize the number of reproductive-aged women who lack access to obstetric care. We define regions with a lack of access as either maternity care deserts, designated by the March of Dimes to be counties with no obstetric care facility or obstetric providers, or regions further than 50 miles from critical care obstetric (CCO) services. We gathered information on hospitals with obstetric services from Georgia Department of Public Health public reports and estimated the female reproductive-age population by census block group using the American Community Survey.

Results

Out of the 1,910,308 reproductive-aged women who live in Georgia, 104,158 (5.5%) live in maternity care deserts, 150,563 (7.9%) reproductive-aged women live further than 50 miles from CCO services, and 38,202 (2.0%) live in both maternity care desert and further than 50 miles from CCO services. Our optimization analysis suggests that at least 56 new obstetric care facilities (a 67% increase) would be required to eliminate maternity care deserts in Georgia. However, and the expansion of 8 facilities would ensure all women in Georgia live within 50 miles of CCO services.

Conclusions

Current measures of access to obstetric care may not be sufficient for evaluating access and planning action toward improvements. In a state like Georgia with a large number of small counties, eliminating maternity care deserts would require a prohibitively large number of new obstetric care facilities. This work suggests that additional measures and tools are needed to estimate the number and type of obstetric care facilities that best match practical resources to meet obstetric care needs.
The impact of cirrhosis on the inflammatory milieu before and long-term after hepatitis C virus elimination by direct-acting antiviral therapy
Authors: Witte Moana , Oltmanns Carlos , Tauwaldt Jan , Schmaus Hagen , Mischke Jasmin , Grabert Gordon , Bretthauer Mara , Deterding Katja , Maasoumy Benjamin , Wedemeyer Heiner , Kacprowski Tim , Kraft Anke R.M. , Cornberg Markus
Published: November 2023

Background and Aims

Chronic hepatitis C virus (HCV) infection can lead to cirrhosis, development of hepatocellular carcinoma (HCC) and several extrahepatic manifestations. A sustained virological response (SVR) is achieved with direct-acting antivirals (DAA) in over 95% of the patients, but sequelae do not improve in all patients, suggesting permanent biological alterations induced by HCV infection. Therefore, we investigated the influence of chronic HCV infection, viral elimination and cirrhosis on inflammatory immune mediators.

Approach and Results

In 102 chronic HCV patients, 46 with and 56 without cirrhosis, 92 soluble immune mediators (SIM) were measured in plasma samples at therapy start, end of treatment and long-term follow-up (median 96 weeks). 39 HBsAg positive persons with HBeAg negative infection served as controls.

At baseline, 42 SIM were altered in chronic HCV patients (adj.p <0.05). Notably, patients with cirrhosis displayed a higher frequency and severity of alterations. At long-term follow-up, the SIM profile of the non-cirrhotic patients recovered to the level of the control group, while 41 SIM remained altered in cirrhotic patients. 33 of these SIM correlated with elastography, among them SIM linked to carcinogenesis as e.g. HGF, IL8 and IL6 (KEGG Pathways hsa05202, hsa05200).

Conclusions

HCV-related changes in the inflammatory milieu can persist even after HCV elimination, specifically in cirrhotic patients. These changes are closely associated with liver damage and carcinogenesis. Our findings underscore the need for HCV elimination before extensive liver injury occurs and suggest further investigation of the relationship between persistent inflammatory milieu changes and long-term sequelae after HCV elimination.

Graphical Abstract