bluuebunny/crossref_metadata_2025_split huggingface dataset:
The evidence against somatotopic organization of function in the primate corticospinal tract
Authors: Lemon Roger N , Morecraft Robert J 
Published: December 2022

Abstract
We review the spatial organization of corticospinal outputs from different cortical areas and how this reflects the varied functions mediated by the corticospinal tract. A long-standing question is whether the primate corticospinal tract shows somatotopical organization. Although this has been clearly demonstrated for corticofugal outputs passing through the internal capsule and cerebral peduncle, there is accumulating evidence against somatotopy in the pyramidal tract in the lower brainstem and in the spinal course of the corticospinal tract. Answering the question on somatotopy has important consequences for understanding the effects of incomplete spinal cord injury.
Our recent study in the macaque monkey, using high-resolution dextran tracers, demonstrated a great deal of intermingling of fibres originating from primary motor cortex arm/hand, shoulder and leg areas. We quantified the distribution of fibres belonging to these different projections and found no significant difference in their distribution across different subsectors of the pyramidal tract or lateral corticospinal tract, arguing against somatotopy. We further demonstrated intermingling with corticospinal outputs derived from premotor and supplementary motor arm areas.
We present new evidence against somatotopy for corticospinal projections from rostral and caudal cingulate motor areas and from somatosensory areas of the parietal cortex. In the pyramidal tract and lateral corticospinal tract, fibres from the cingulate motor areas overlap with each other. Fibres from the primary somatosensory cortex arm area completely overlap those from the leg area. There is also substantial overlap of both these outputs with those from posterior parietal sensorimotor areas.
We argue that the extensive intermingling of corticospinal outputs from so many different cortical regions must represent an organizational principle, closely related to its mediation of many different functions and its large range of fibre diameters.
The motor sequelae of incomplete spinal injury, such as central cord syndrome and ‘cruciate paralysis’, include much greater deficits in upper than in lower limb movement. Current teaching and text book explanations of these symptoms are still based on a supposed corticospinal somatotopy or ‘lamination’, with greater vulnerability of arm and hand versus leg fibres. We suggest that such explanations should now be finally abandoned. Instead, the clinical and neurobiological implications of the complex organization of the corticospinal tract need now to be taken into consideration. This leads us to consider the evidence for a greater relative influence of the corticospinal tract on upper versus lower limb movements, the former best characterized by skilled hand and digit movements.
miR-132-3p regulates antibody-mediated complement-dependent cytotoxicity in colon cancer cells by directly targeting CD55
Authors: Fan Yu , Liao Juan , Wang Yu , Wang Zhu , Zheng Hong , Wang Yanping 
Published: December 2022

AbstractThe overexpression of membrane-bound complement regulatory proteins (mCRPs) on tumour cells helps them survive complement attacks by suppressing antibody-mediated complement-dependent cytotoxicity (CDC). Consequently, mCRP overexpression limits monoclonal antibody drug immune efficacy. CD55, an mCRP, plays an important role in inhibiting antibody-mediated CDC. However, the mechanisms regulating CD55 expression in tumour cells remain unclear. Here, the aim was to explore CD55-targeting miRNAs. We previously constructed an in vitro model comprising cancer cell lines expressing α-gal and serum containing natural antibodies against α-gal and complement. This was used to simulate antibody-mediated CDC in colon cancer cells. We screened microRNAs that directly target CD55 using LoVo and Ls-174T colon cell lines, which express CD55 at low and high levels, respectively. miR-132-3p expression was dramatically lower in Ls-174T cells than in LoVo cells. miR-132-3p overexpression or inhibition transcriptionally regulated CD55 expression by specifically targeting its mRNA 3ʹ-untranslated regions. Further, miR-132-3p modulation regulated colon cancer cell sensitivity to antibody-mediated CDC through C5a release and C5b-9 deposition. Moreover, miR-132-3p expression was significantly reduced, whereas CD55 expression was increased, in colon cancer tissues compared to levels in adjacent normal tissues. CD55 protein levels were negatively correlated with miR-132-3p expression in colon cancer tissues. Our results indicate that miR-132-3p regulates colon cancer cell sensitivity to antibody-mediated CDC by directly targeting CD55. In addition, incubating the LoVo human tumour cell line, stably transfected with the xenoantigen α-gal, with human serum containing natural antibodies comprises a stable and cheap in vitro model to explore the mechanisms underlying antibody-mediated CDC.
Gingival transcriptomic patterns of macrophage polarization during initiation, progression, and resolution of periodontitis
Authors: Gonzalez Octavio A , Kirakodu Sreenatha S , Nguyen Linh M , Ebersole Jeffrey L 
Published: December 2022

AbstractPhenotypic and functional heterogeneity of macrophages is clearly a critical component of their effective functions in innate and adaptive immunity. This investigation hypothesized that altered profiles of gene expression in gingival tissues in health, disease, and resolution would reflect changes in macrophage phenotypes occurring in these tissues. The study used a nonhuman primate model to evaluate gene expression profiles as footprints of macrophage variation using a longitudinal experimental model of ligature-induced periodontitis in animals from 3 to 23 years of age to identify aging effects on the gingival environment. Significant differences were observed in distribution of expressed gene levels for M0, M1, and M2 macrophages in healthy tissues with the younger animals showing the least expression. M0 gene expression increased with disease in all but the aged group, while M1 was increased in adult and young animals, and M2 in all age groups, as early as disease initiation (within 0.5 months). Numerous histocompatibility genes were increased with disease, except in the aged samples. An array of cytokines/chemokines representing both M1 and M2 cells were increased with disease showing substantial increases with disease initiation (e.g. IL1A, CXCL8, CCL19, CCL2, CCL18), although the aged tissues showed a more limited magnitude of change across these macrophage genes. The analytics of macrophage genes at sites of gingival health, disease, and resolution demonstrated distinct profiles of host response interactions that may help model the disease mechanisms occurring with the formation of a periodontal lesion.
Estimating the relationship between liquid- and vapor-phase odorant concentrations using a photoionization detector (PID)-based approach
Authors: Jennings Liam , Williams Ellie , Caton Samuel , Avlas Marta , Dewan Adam 
Published: December 2022

Abstract
Olfactory studies frequently utilize odor stimuli consisting of volatiles created from liquid dilutions of various chemicals. A problem arises if the researcher relies on these liquid dilutions to extrapolate vapor concentrations based on ideal gas behavior. For most chemicals, the relationship between liquid and vapor concentration deviates from these laws of proportionality due to interactions between the chemical and the solvent. Here, we describe a method to estimate vapor-phase concentrations of diluted odorants using a photoionization detector. To demonstrate the utility of this method, we assessed the relationship between liquid-/vapor-phase concentrations for 14 odorants (7 alcohols, 1 ester, and 6 aldehydes) in 5 different solvents (water, mineral oil, diethyl phthalate, dipropylene glycol, and propylene glycol). An analysis of 7 additional esters is also included to assess how carbon chain length and functional group, interacts with these solvents (for a total of 105 odorant/solvent pairs). Our resulting equilibrium equations successfully corrected for behavioral sensitivity differences observed in mice tested with the same odorant in different solvents and were overall similar to published measurements using a gas chromatography-based approach. In summary, this method should allow researchers to determine the vapor-phase concentration of diluted odorants and will hopefully assist in more accurate comparisons of odorant concentrations across olfactory studies.
Bartonella quintanaTransmitted by Head Lice: An Outbreak of Trench Fever in Senegal
Authors: Hammoud Alissa , Louni Meriem , Fenollar Florence , Bassene Hubert , Sambou Masse , Duclos Nathalie , Diatta Georges , Sokhna Cheikh , Levasseur Anthony , Raoult Didier , Mediannikov Oleg 
Published: December 2022

AbstractBackgroundLouse-borne trench fever caused by Bartonella quintana is a neglected public health concern, known to be transmitted from body louse feces via scratching. No viable B. quintana have ever been isolated from head lice before; therefore, their role as a vector is still poorly understood.MethodsIn Senegal, the implementation of a permanent local surveillance system in a point-of-care laboratory (POC) allows the monitoring of emerging diseases. Here we used culture as well as molecular and genomic approaches to document an outbreak of trench fever associated with head lice in the village of Ndiop. Head lice and blood samples were collected from febrile patients between November 2010 and April 2015. Genomes of 2 isolated strains of B. quintana were sequenced and analyzed.ResultsA total of 2289 blood samples were collected in the 2010–2015 period. From 2010–2013, B. quintana DNA was detected by polymerase chain reaction (PCR) in 0.25% (4/1580). In 2014, 228 blood samples were collected, along with 161 head lice from 5 individuals. B. quintana DNA was detected in 4.4% (10/228) of blood samples, and in lice specimens collected from febrile patients (61.7%, 50/81) and non-febrile patients (61.4%, 43/70). Two B. quintana strains were isolated from blood and head lice from 2 different patients. Genomic sequence analysis showed 99.98% overall similarity between both strains.ConclusionsThe presence of live B. quintana in head lice, and the genetic identity of strains from patients’ blood and head lice during a localized outbreak in Senegal, supports the evidence of head lice vectorial capacity.
The use of Vaccinia Immune Globulin in the Treatment of Severe Mpox. Virus Infection in Human Immunodeficiency Virus/AIDS
Authors: Thet Andrea K , Kelly Paul J , Kasule Sabirah N , Shah Anish K , Chawala Arpan , Latif Amber , Chilimuri Sridhar S , Zeana Cosmina B 
Published: December 2022

Abstract
We report a case of progressive, severe mpox virus (MPXV) infection in a patient with AIDS despite a standard course of tecovirimat. He significantly improved after administration of vaccinia immune globulin intravenous (VIGIV) highlighting its use as an adjunct for severe disease in immunocompromised hosts.
Three Cases of Non-compliance: Challenges of Trust and Governmental Response Strategies
Authors: Liang Bin 
Published: December 2022

Abstract
This study examines three noncompliant cases occurred in Wuhan, China during the outbreak of the COVID-19 in 2020, including the Li Wenliang (李文亮) case, the Chen Qiushi (陈秋实) case, and the Huang Dengying (黄登英) case. These cases, albeit with different natures, broke out during the early stage of Wuhan &#x99;s epidemic and posted threat and challenges to the Chinese authorities to different degrees. Based on open source information, this study focuses on the issues of trust and examines trust at three different levels (interpersonal trust, public trust, and political trust) among interactions by three groups of actors, including individuals involved in each case, the general public (e.g., how the public perceived and evaluated each case), and the authorities (e.g., how governments at the local and central levels perceived and handled each case). Two research questions are addressed: 1) How did trust at different levels play out in each case? 2) How did Chinese authorities respond to and handle threat and public trust challenges? Policy implications are drawn.
UpStreAm doxycycline in ST-eLeVation myocArdial infarction: targetinG infarct hEaling and ModulatIon (SALVAGE-MI trial)
Authors: Noaman Samer , Neil Christopher , O’Brien Jessica , Frenneaux Michael , Hare James , Wang Bing , Yee Tai Tsin , Theuerle James , Shaw James , Stub Dion , Bloom Jason , Walton Antony , Duffy Stephen J , Peter Karl-Heinz , Cox Nicholas , Kaye David M , Taylor Andrew , Chan William 
Published: December 2022

AbstractAimsExperimental studies demonstrate protective effects of doxycycline on myocardial ischaemia-reperfusion injury. The trial investigated whether doxycycline administered prior to reperfusion in patients presenting with ST-elevation myocardial infarction (STEMI) reduces infarct size (IS) and ameliorates adverse left ventricular (LV) remodelling.Methods and resultsIn this randomized, double-blind, placebo-controlled trial, patients presenting with STEMI undergoing primary percutaneous coronary intervention (PPCI) were randomized to either intravenous doxycycline or placebo prior to reperfusion followed by 7 days of oral doxycycline or placebo. The primary outcome was final IS adjusted for area-at-risk (fIS/AAR) measured on two cardiac magnetic resonance scans ∼6 months apart. Of 103 participants, 50 were randomized to doxycycline and 53 to placebo and were matched for age (59 ± 12 vs. 60 ± 10 years), male sex (92% vs. 79%), diabetes mellitus (26% vs. 11%) and left anterior descending artery occlusion (50% vs. 49%), all P &gt; 0.05. Patients treated with doxycycline had a trend for larger fIS/AAR [0.79 (0.5–0.9) vs. 0.61 (0.47–0.76), P = 0.06], larger fIS at 6 months [18.8% (12–26) vs. 13.6% (11–21), P = 0.08], but similar acute IS [21.7% (17–34) vs. 19.4% (14–27), P = 0.19] and AAR [26% (20–36) vs. 24.7% (16–31), P = 0.22] compared with placebo. Doxycycline did not ameliorate adverse LV remodelling [%Δend-diastolic volume index, 1.1% (−3.8–8.4) vs. −1.34% (−6.1–5.8), P = 0.42] and was independently associated with larger fIS (regression coefficient = 0.175, P = 0.03).ConclusionDoxycycline prior to PPCI neither reduced IS acutely or at six months nor attenuated adverse LV remodelling. These data raise safety concerns regarding doxycycline use in STEMI for infarct modulation and healing.
Lower testosterone levels are associated with higher risk of death in men
Authors: Muehlenbein Michael P , Gassen Jeffrey , Shattuck Eric C , Sparks Corey S 
Published: December 2022

AbstractBackground and ObjectivesTestosterone plays an important role in regulating male development, reproduction and health. Declining levels across the lifespan may reflect, or even contribute to, chronic disease and mortality in men.MethodologyRelationships between testosterone levels and male mortality were analyzed using data from multiple samples of the cross-sectional National Health and Nutrition Examination Survey (n = 10 225). Target outcomes included known deaths from heart disease, malignant neoplasms, chronic lower respiratory diseases, cerebrovascular diseases, Alzheimer’s disease, diabetes mellitus, influenza and pneumonia, kidney diseases, and accidents or unintentional injuries.ResultsResults of discrete-time hazard models revealed that lower levels of testosterone were related to higher mortality for the majority of disease categories in either an age-dependent or age-independent fashion. Analysis of all-cause mortality—which included deaths from any known disease—also revealed greater general risk for those with lower testosterone levels. For most disease categories, the hazard associated with low testosterone was especially evident at older ages when mortality from that particular ailment was already elevated. Notably, testosterone levels were not related to mortality risk for deaths unrelated to chronic disease (i.e. accidents and injuries).Conclusions and ImplicationsWhile the causal direction of relationships between testosterone and mortality risk remains unclear, these results may reflect the decline in testosterone that accompanies many disease states. Accordingly, the relationship between testosterone and male mortality may be indirect; ill individuals are expected to have both lower testosterone and higher mortality risk.
Eigenvalue bounds for double saddle-point systems
Authors: Bradley Susanne , Greif Chen 
Published: December 2022

Abstract
We derive bounds on the eigenvalues of a generic form of double saddle-point matrices. The bounds are expressed in terms of extremal eigenvalues and singular values of the associated block matrices. Inertia and algebraic multiplicity of eigenvalues are considered as well. The analysis includes bounds for preconditioned matrices based on block diagonal preconditioners using Schur complements, and it is shown that in this case the eigenvalues are clustered within a few intervals bounded away from zero. Analysis for approximations of Schur complements is included. Some numerical experiments validate our analytical findings.
The Self-Assembled Skin Substitute History: Successes, Challenges, and Current Treatment Indications
Authors: Dagher Jason , Arcand Charles , Auger François A , Germain Lucie , Moulin Véronique J 
Published: December 2022

Abstract
The self-assembled skin substitute (SASS) is an autologous bilayered skin substitute designed by our academic laboratory, the Laboratoire d’Organogenèse Expérimentale (LOEX) to offer definitive treatment for patients lacking donor sites (unwounded skin) to cover their burn wounds. This product shows skin-like attributes, such as an autologous dermal and epidermal layer, and is easily manipulable by the surgeon. Its development stems from the need for skin replacement in high total body surface area burned survivors presenting few donor sites for standard split-thickness skin grafting. This review aims to present the history, successes, challenges, and current therapeutic indications of this skin substitute. We review the product’s development history, before discussing current production techniques, as well as clinical use. The progression observed since the initial SASS production technique described in 1999, up to the most recent technique expresses significant advances made in the technical aspect of our product, such as the reduction of the production time. We then explore the efficacy and benefits of SASS over existing skin substitutes and discuss the outcomes of a recent study focusing on the successful treatment of 14 patients. Moreover, an ongoing cross-Canada study is further assessing the product’s safety and efficacy. The limitations and technical challenges of SASS are also discussed.
Skin Tissue Engineering Advances in Burns: A Brief Introduction to the Past, the Present, and the Future Potential
Authors: Chogan Faraz , Chen Yufei , Wood Fiona , Jeschke Marc G 
Published: December 2022

Abstract
Burn injuries are a severe form of skin damage with a significant risk of scarring and systemic sequelae. Approximately 11 million individuals worldwide suffer burn injuries annually, with 180,000 people dying due to their injuries. Wound healing is considered the main determinant for the survival of severe burns and remains a challenge. The surgical treatment of burn wounds entails debridement of necrotic tissue, and the wound is covered with autologous skin substitutes taken from healthy donor areas. Autologous skin transplantation is still considered to be the gold standard for wound repair. However, autologous skin grafts are not always possible, especially in cases with extensive burns and limited donor sites. Allografts from human cadaver skin and xenografts from pig skin may be used in these situations to cover the wounds temporarily. Alternatively, dermal analogs are used until permanent coverage with autologous skin grafts or artificial skins can be achieved, requiring staged procedures to prolong the healing times with the associated risks of local and systemic infection. Over the last few decades, the wound healing process through tissue-engineered skin substitutes has significantly enhanced as the advances in intensive care ensuring early survival have led to the need to repair large skin defects. The focus has shifted from survival to the quality of survival, necessitating accelerated wound repair. This special volume of JBCR is dedicated to the discoveries, developments, and applications leading the reader into the past, present, and future perspectives of skin tissue engineering in burn injuries.
The Role of Cell-Based Therapies in Acute Burn Wound Skin Repair: A Review
Authors: Wood Fiona M 
Published: December 2022

AbstractTissue engineering solutions for skin have been developed over the last few decades with a focus initially on a two-layered structure with epithelial and dermal repair. An essential element of skin restoration is a source of cells capable of differentiating into the appropriate phenotype. The need to repair areas of skin when traditional techniques were not adequate addressed led to cell based therapies being developed initially as a laboratory-based tissue expansion opportunity, both as sheets of cultured epithelial autograft and in composite laboratory-based skin substitutes. The time to availability of the cell-based therapies has been solved in a number of ways, from using allograft cell-based solutions to the use of point of care skin cell harvesting for immediate clinical use. More recently pluripotential cells have been explored providing a readily available source of cells and cells which can express the broad range of phenotypes seen in the mature skin construct. The lessons learnt from the use of cell based techniques has driven the exploration of the use of 3D printing technology, with controlled accurate placement of the cells within a specific printed construct to optimise the phenotypic expression and tissue generation.
Observations of nemaline bodies in muscle biopsies of critically ill patients infected with SARS-CoV-2
Authors: Vandenabeele Frank , Stevens Sjoerd , Snijders Tim , Stessel Björn , Dubois Jasperina , van Loon Luc J C , Lambrichts Ivo , Agten Anouk 
Published: December 2022

Abstract
Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who have been admitted to the intensive care unit (ICU) often face months of physical disability after discharge. To optimize recovery, it is important to understand the role of musculoskeletal alterations in critically ill patients infected with SARS-CoV-2. The main aim of the present study was to describe the presence and morphology of nemaline bodies found in the skeletal muscle tissue from critically ill patients infected with SARS-CoV-2. In n = 7 patients infected with SARS-CoV-2, ultrastructural characteristics of vastus lateralis muscle obtained on days 1–3 and days 5–8 following ICU admission were investigated in more detail with electron microscopy. Those muscle biopsies consistently showed variable degrees of myofiber necrosis and myofibrillar disorganization. In 4/7 (57%) patients on days 5–8, the Z-line material accumulated into nemaline bodies with a typical lattice-like appearance at higher magnification, similar to that found in nemaline myopathy. This study is the first to describe the disintegration of myofibrils and the accumulation of Z-line material into nemaline bodies in the skeletal muscle tissue obtained from critically ill coronavirus disease-19 patients following ICU admission, which should be interpreted primarily as a non-specific pathological response of extreme myofibrillar disintegration associated with myofiber necrosis.