bluuebunny/crossref_metadata_2025 huggingface dataset:
Three enzymes of Rhizobium radiobacter involved in the novel metabolism of two naturally occurring bioactive oxidative derivatives of l-isoleucine
Authors: Fujii Hidemi , Hibi Makoto , Shimizu Sakayu , Yokozeki Kenzo , Ogawa Jun
Published: July 2022

Rhizobium radiobacter C58 was found to convert 4-hydroxyisoleucine (HIL) and 2-amino-3-methyl-4-ketopentanoate (AMKP), bioactive oxidative derivatives of l-isoleucine, in both cases producing 2-aminobutyrate. Three native enzymes involved in these metabolisms were purified by column chromatography and successfully identified. In this strain, HIL was converted to acetaldehyde and 2-aminobutyrate by coupling action of the transaminase rrIlvE and the aldolase HkpA. AMKP was also converted to acetate and 2-aminobutyrate by coupling action of rrIlvE and a hydrolase DkhA. In the multi-enzymatic reactions, HkpA catalyzes the retro-aldol reaction of 4-hydroxy-3-methyl-2-ketopentanoate into acetaldehyde and 2-ketobutyrate, and DkhA catalyzes hydrolytic cleavage of the carbon-carbon bond of 2,4-diketo-3-methylpentanoate into acetate and 2-ketobutyrate. rrIlvE catalyzes reversible transamination between HIL and 4-hydroxy-3-methyl-2-ketopentanoate, AMKP and 2,4-diketo-3-methylpentanoate, and 2-ketobutyrate and 2-aminobutyrate. The results suggested that the conversion activity of Rhizobium bacteria plays an important role in the complex biological metabolic networks associated with HIL and AMKP.
Biological Random Walks: multi-omics integration for disease gene prioritization
Authors: Gentili Michele , Martini Leonardo , Sponziello Marialuisa , Becchetti Luca
Published: July 2022

Motivation

Over the past decade, network-based approaches have proven useful in identifying disease modules within the human interactome, often providing insights into key mechanisms and guiding the quest for therapeutic targets. This is all the more important, since experimental investigation of potential gene candidates is an expensive task, thus not always a feasible option. On the other hand, many sources of biological information exist beyond the interactome and an important research direction is the design of effective techniques for their integration.

Results

In this work, we introduce the Biological Random Walks (BRW) approach for disease gene prioritization in the human interactome. The proposed framework leverages multiple biological sources within an integrated framework. We perform an extensive, comparative study of BRW’s performance against well-established baselines.

Availability and implementation

All codes are publicly available and can be downloaded at https://github.com/LeoM93/BiologicalRandomWalks. We used publicly available datasets, details on their retrieval and preprocessing are provided in the Supplementary Material.

Supplementary information

Supplementary data are available at Bioinformatics online.
Identification of cell-type-specific spatially variable genes accounting for excess zeros
Authors: Yu Jinge , Luo Xiangyu
Published: July 2022

Motivation

Spatial transcriptomic techniques can profile gene expressions while retaining the spatial information, thus offering unprecedented opportunities to explore the relationship between gene expression and spatial locations. The spatial relationship may vary across cell types, but there is a lack of statistical methods to identify cell-type-specific spatially variable (SV) genes by simultaneously modeling excess zeros and cell-type proportions.

Results

We develop a statistical approach CTSV to detect cell-type-specific SV genes. CTSV directly models spatial raw count data and considers zero-inflation as well as overdispersion using a zero-inflated negative binomial distribution. It then incorporates cell-type proportions and spatial effect functions in the zero-inflated negative binomial regression framework. The R package pscl is employed to fit the model. For robustness, a Cauchy combination rule is applied to integrate P-values from multiple choices of spatial effect functions. Simulation studies show that CTSV not only outperforms competing methods at the aggregated level but also achieves more power at the cell-type level. By analyzing pancreatic ductal adenocarcinoma spatial transcriptomic data, SV genes identified by CTSV reveal biological insights at the cell-type level.

Availability and implementation

The R package of CTSV is available at https://bioconductor.org/packages/devel/bioc/html/CTSV.html.

Supplementary information

Supplementary data are available at Bioinformatics online.
There is Room for Encouraging Conversion in the Scope of Bioethics Expertise
Authors: Brown Nathaniel J
Published: July 2022

The American Society for Bioethics and Humanities has developed a curriculum leading to a certificate in health care ethics consultation. A certification in ethics consultation initially seems to fit nicely into the biomedical model of clinical expertise espoused by modern biomedicine, but examining what exactly constitutes moral expertise, particularly for traditional Christians, reveals a significant problem: the certification relies on an implicit view of ethics as essentially procedural. It leaves virtually all serious moral content to be filled in, if at all, after an ostensibly neutral scaffolding has been erected. Such an approach does not help answer deep moral questions about how one should live, and it is these questions that ought to be encouraged during some conflicts that result in requests for ethics consultations. This paper suggests that, in certain circumstances, and for a subset of patients, encouraging conversion can help remedy the deficiency of an overly mechanized approach. A system open to conversion would have more room for Traditional Christians, regardless of the outcome, as it would take morality as lived, communal experience more seriously and help others, if desired, to do so as well.
Persistent Severe Acute Respiratory Syndrome Coronavirus 2 Infection With accumulation of mutations in a patient with poorly controlled Human Immunodeficiency Virus infection
Authors: Maponga Tongai G , Jeffries Montenique , Tegally Houriiyah , Sutherland Andrew , Wilkinson Eduan , Lessells Richard J , Msomi Nokukhanya , van Zyl Gert , de Oliveira Tulio , Preiser Wolfgang
Published: July 2022

A 22-year-old woman with uncontrolled advanced human immunodeficiency virus (HIV) infection was persistently infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) beta variant for 9 months, the virus accumulating >20 additional mutations. Antiretroviral therapy suppressed HIV and cleared SARS-CoV-2 within 6 to 9 weeks. Increased vigilance is warranted to benefit affected individuals and prevent the emergence of novel SARS-CoV-2 variants.
Multi-View Spatial–Temporal Graph Neural Network for Traffic Prediction
Authors: Li He , Jin Duo , Li XueJiao , Huang HongJie , Yun JinPeng , Huang LongJi
Published: July 2022

Spatial–temporal graph neural network has drawn more and more attention in recent years and is widely used to various real-world applications. However, learning the spatial–temporal graph neural network structure presents unique challenges including: (i) the dynamic spatial correlation; (ii) the dynamic temporal correlation. Even the existing methods take into account the spatial correlation, they still learn the static road network structure information, which cannot reflect the dynamic of road relations. Some of the works has focused on modeling the long-term time series, but the improvements have been limited tightly. To overcome these challenges, we proposed a novel approach called Multi-View Spatial–Temporal Graph Neural Network. Differ from the existing research, we designed a multi-view temporal transformer module to extract dynamic temporal correlation and enhance the expression of medium and long-term temporal features. We propose a multi-view spatial structure and a corresponding multi-view graph convolutional module, which are capable of simultaneously combining the features of static road network structure and dynamic changes. Compared with 11 baselines, our proposed model has achieved significant improvement in the accuracy of prediction.
Production of parchment legal deeds in England, 1690–1830
Authors: Doherty Sean Paul , Henderson Stuart
Published: July 2022

Biomolecular analysis of historical parchment legal documents is providing new insight into their production and use. Successful interpretation of this data is dependent on understanding if the location and date written on the document accurately reflect where the animal from which the parchment was produced was raised and when it died. Our analysis reveals that the location the deed concerns, or that of the stationer through whom it was sold, typically bears no relation to the animal’s origin, but that the date the agreement was signed was probably only a few months after the animal’s death.
Competition policy and black empowerment: South Africa’s path to inclusion
Authors: Mncube Liberty , Ratshisusu Hardin
Published: July 2022

The first democratic government of South Africa prioritized the transformation of society on a non-racial, democratic, and local foundation. The expectation was that all law in South Africa would contribute to, amongst other things, economic transformation and redress the imbalances created by past racial divisions, and more important foster the participation of the previously marginalized people to participate in the mainstream economy. The Competition Act is part of this fabric. In the twenty years that have passed, South Africa has become a leader in the developing world. This article provides a critical review of how competition law has pursued black empowerment with a particular focus on current challenges and opportunities.
Phylogeny of the Turkic Languages Inferred from Basic Vocabulary: Limitations of the Lexicostatistical Methods in an Intensive Contact Situation
Authors: Egorov Ilya M , Dybo Anna V , Kassian Alexei S
Published: July 2022

This article provides an attempt to revise the phylogenetic structure of the Turkic family using a computational lexicostatistical approach. The methodological framework of the present research is characterized by the following features: (1) wordlists with strictly controlled semantics; (2) step-by-step reconstruction using Swadesh wordlists for proto-languages; (3) three stages of post-processing of the input data (analysis of root cognacy, elimination of derivational drift, and optimization of homoplasy); (4) application of several computational algorithms (Starling neighbor-joining, Bayesian MCMC, and maximum parsimony). The analysis provided confirms the status of Chuvash as the first outlier and suggests a subsequent multifurcation of Proto-Nuclear-Turkic into eight branches. The Siberian Turkic group is a purely areal unity, that is, Yakut-Dolgan, Tofa-Tuvinian, Khakas-Mrassu, Sarygh Yugur and Altai do not form a clade. Altai is grouped together with the Kipchak languages as a separate taxon; it does not show a particularly close relationship with Kirghiz, which belongs to another Kipchak subgroup. Karluk is a low-level taxon inside the Kipchak clade.
Exploration of the response of soil properties and plant species composition to centuries-old traditional meadow irrigation
Authors: Gerlach Rebekka , Buhk Constanze , Schirmel Jens , Jungkunst Hermann F
Published: July 2022

Only targeted and sustainable management will preserve extensively managed grasslands, one of Europe’s most species-rich habitats. Traditionally, largely abandoned irrigation might prove a sustainable management strategy, but the understanding of the interactions among irrigation, soil properties and plant species are low for a generally humid ecoregion. We aimed at advancing our understanding of plant ecology by disentangling plant community responses to traditional lowland meadow irrigation from traditionally low fertilization rates. We studied plant composition and diversity jointly with the underlying links to soil properties (Corg, total N, water holding capacity and mesofaunal activity) and soil nutrients (Nmin, P, K, Mg and B). In a field study, we compared 13 long-term traditionally irrigated and 13 non-irrigated (17 fertilized and 9 non-fertilized) meadows. We surveyed plant diversity, composition and soil nutrients as well as soil properties for 1 year assuming low annual variation. Irrigation and fertilization led to differences in soil properties and soil nutrients without impact on sheer plant species diversity but on plant species composition. Finer grain sizes due to siltation increased water holding capacity and nutrient storage. Hence, resource-acquisitive graminoid species had advantages in irrigated meadows. Thus, irrigation is not only a mean to preserve biodiversity of extensively used meadows of Central Europe but may prove a tool to differentiate between plant functional traits.
Should iterative spinal surgeries be performed? A case report
Authors: Ampat George , Rhodes Samantha J , Sims Jonathan MG , Wyman Emily
Published: July 2022

The number of spinal surgeries performed is increasing. Along with this comes an increase in iterative surgeries. Each surgery that a patient undergoes has an increased risk of complication and a decreased success rate compared to the last. We present a case of a 51-year-old female who continues to experience debilitating low back pain following three double fusions performed over four years. The patient describes that she is in more pain now than before any previous surgical intervention. Following these surgeries, the patient has been forced to take early retirement, frequently uses a wheelchair and requires assistance with daily activities. The role of iterative surgery in healthcare needs to be re-assessed. The poor outcomes, especially following tertiary and quaternary surgery, question the use of iterative surgery entirely.
Multisite biologic tissue SARS-CoV-2 PCR testing in kidney transplantation from a COVID-positive donor
Authors: Zhang Jared R , Kueht Michael , Lea A Scott , Stevenson Heather L , Gosnell Joseph , Ren Ping , Nielsen Marisa C , Miller Aaron , Mujtaba Muhammad , Fair Jeffrey
Published: July 2022

With a high community transmission rate, SARS-CoV-2 has profoundly exacerbated the shortage of organs. Although the risk of donor-recipient transmission of SARS-CoV-2 is anecdotally low, an organ-specific infection analysis of procured organs from SARS-CoV-2 positive donors has yet to be established. Using a combination of clinically available and research-only polymerase chain reaction methods, organ preservation fluid and renal parenchymal tissues were tested for SARS-CoV-2 from the kidney of a SARS-CoV-2-positive donor prior to transplantation. The recipient has remained SARS-CoV-2 negative and clinically well, with excellent graft function 120 days post-transplantation.
Hydrocele in the canal of nuck in a young female: a rare case report
Authors: Sood Rajan , Trivedi Sourabh , Tanwar Paran
Published: July 2022

Hydrocele of the canal of Nuck is a rare condition seen in younger females which is an extension of the peritoneum into the inguinal canal. Incomplete proximal obliteration and collection of serous fluid in the sac leads to the formation of a hydrocele of the canal of Nuck. A 28-year-old woman presented with swelling in her right groin for 5 months of 6cm × 5 cm. Ultrasound revealed a well-defined tubular cystic structure, measuring 5 cm × 3.5 cm × 5 cm with a volume of 50–60 ml. The cyst was dissected and the neck of the sac was extended up to the deep ring. Clear fluid was found on opening the sac. Clinically, it appears either as a painless or a moderately painful fluctuant inguinal mass. Clinical findings alone do not help in diagnosing the disease. Treatment includes surgical excision of the mass but without puncturing it as aspiration is inadequate and results in recurrence.
LEAfing through literature: late embryogenesis abundant proteins coming of age—achievements and perspectives
Authors: Hernández-Sánchez Itzell E , Maruri-López Israel , Martinez-Martinez Coral , Janis Brett , Jiménez-Bremont Juan Francisco , Covarrubias Alejandra A , Menze Michael A , Graether Steffen P , Thalhammer Anja
Published: July 2022

To deal with increasingly severe periods of dehydration related to global climate change, it becomes increasingly important to understand the complex strategies many organisms have developed to cope with dehydration and desiccation. While it is undisputed that late embryogenesis abundant (LEA) proteins play a key role in the tolerance of plants and many anhydrobiotic organisms to water limitation, the molecular mechanisms are not well understood. In this review, we summarize current knowledge of the physiological roles of LEA proteins and discuss their potential molecular functions. As these are ultimately linked to conformational changes in the presence of binding partners, post-translational modifications, or water deprivation, we provide a detailed summary of current knowledge on the structure–function relationship of LEA proteins, including their disordered state in solution, coil to helix transitions, self-assembly, and their recently discovered ability to undergo liquid–liquid phase separation. We point out the promising potential of LEA proteins in biotechnological and agronomic applications, and summarize recent advances. We identify the most relevant open questions and discuss major challenges in establishing a solid understanding of how these intriguing molecules accomplish their tasks as cellular sentinels at the limits of surviving water scarcity.
A proposed alternative dynamical history for 2P/Encke that explains the taurid meteoroid complex
Authors: Egal A , Wiegert P , Brown P G
Published: July 2022

The Taurid Meteoroid Complex (TMC) is a broad stream of meteoroids that produces several annual meteor showers on Earth. If the linkage between these showers and 2P/Encke is at the centre of most TMC models, the small size and low activity of the comet suggest that 2P/Encke is not the unique parent body of the Taurids. Here, we simulate the formation of the TMC from 2P/Encke and several NEAs. In total, we explored more than a hundred stream formation scenarios using clones of 2P/Encke. Each modelled stream was integrated and compared with present-day Taurid observations. As previously reported, we find that even slight variations of 2P/Encke’s orbit modifie considerably the characteristics of the simulated showers. Most of the comet’s clones, including the nominal one, appear to reproduce the radiant structure of the Taurid meteors but do not match the observed time and duration of the showers. However, the radiants and timing of most Taurid showers are well reproduced by a particular clone of the comet. Our analysis thus suggest that with this specific dynamical history, 2P/Encke is the sole parent of the four major TMC showers that have ages from 7 to 21 ka. Our modelling also predicts that the 2022 Taurid Resonant Swarm return will be comparable in strength to the 1998, 2005, and 2015 returns. While purely dynamical models of Encke’s orbit – limited by chaos – may fail to reveal the comet’s origin, its meteor showers may provide the trail of breadcrumbs needed to backtrack our way out of the labyrinth.
Inappropriate secretion of fibroblast growth factor 23 despite hypophosphataemia with changes in bone turnover markers in a girl with systemic lupus erythematosus: Case report and review of the literature
Authors: Kawaguchi Tadayasu , Inamo Yasuji
Published: July 2022

We report an 11-year-old girl with systemic lupus erythematosus (SLE) who showed hypophosphataemia (1.7 mg/dl, normal range: 3.9–5.8 mg/dl), a decrease in the tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (0.77 mg/dl, normal range: 3.4–5.6 mg/dl), and an elevated serum fibroblast growth factor 23 (FGF23) (circulating phosphate-regulatory hormone) concentration (FGF23: 282 pg/ml, normal range: <52 pg/ml) at the onset. The patient was treated with intravenous pulse methylprednisolone, oral prednisolone, mycophenolate mofetil, hydroxychloroquine, and phosphorus supplement. Serum FGF23 concentrations decreased to near the reference value at 5 months after the onset of SLE, and the TmP/GFR (4.61 mg/dl) simultaneously improved. The urinary deoxypyridinoline (bone resorption marker) concentration on admission (18.9 nmol/mmol creatinine, normal range: 75.4 ± 6.8 nmol/mmol creatinine) was greatly reduced, and the bone-type alkaline phosphatase (bone formation marker) concentration (30.6 µg/l, normal range: 58.6 ± 15.3 µg/l) was also reduced during the increase in FGF23 concentrations before steroid therapy was initiated. The reason for the inappropriate secretion of FGF23, despite hypophosphataemia, remains unknown. The findings in our case suggest that changes in bone turnover markers can occur in patients with SLE and excess inappropriate secretion of FGF23, despite severe and persistent hypophosphataemia.
The Impact of a Music Therapy Support Group on Perceived Stress, Anxiety, and Depression in Long-Term Caregivers: A Pilot Study
Authors: Denk Jennifer G
Published: July 2022

Family members caring for loved ones with Alzheimer’s disease, Parkinson’s disease, or dementia have described elevated levels of stress, anxiety, or depression. Studies have reported the effectiveness of support groups for caregivers in addressing these symptoms. The purpose of this pilot study was to examine the impact of a music therapy support group on the perceived stress, anxiety, and depression of caregivers of loved ones with Alzheimer’s disease, Parkinson’s disease, or dementia. Four female adults (n = 62.50 years, SD = 14.15) participated in multiple music therapy support group sessions. Participants completed 3 visual analog scales rating perceived stress, anxiety, and depression at the beginning and end of each session. Results showed trends of stress, anxiety, and depression ratings decreasing from pre- to post-session in all but one session, in which pretest scores for depression were 0 and remained unchanged. Following the completion of the final music therapy support group, 2 participants engaged in a focus group which yielded 2 themes pertinent to the study purpose: receiving support from group members, and personal support strategies employed outside of the music therapy support group sessions. Focus group and pre- and post-session results support the potential benefit of a music therapy support group on acute feelings of stress, anxiety, and depression in long-term caregivers. Due to the low number of participants, these findings suggest that additional investigations are necessary to adequately establish the effectiveness of a music therapy support group for caregivers of loved ones with Alzheimer’s disease, Parkinson’s disease, or dementia.
KIT-Associated Familial GIST Syndrome: Response to Tyrosine Kinase Inhibitors and Implications for Risk Management
Authors: Brodey Alexandra , Kounnis Valentinos , Hawkes Lara , Jones Robin L , McVeigh Terri P , Cojocaru Elena
Published: July 2022

Sporadic gastrointestinal stromal tumors (GIST) are rare tumors, with a median age at diagnosis of 60 years. Familial GISTs are very rare and typically associated with earlier onset, with an average age at diagnosis of 48 years. To date, just over 50 familial cases associated with a germline variant KIT or PDGFRa genes have been published. Therefore, there are many challenges in managing these patients, including the timing of starting systemic treatment, considering that most patients have been asymptomatic for a long period before being diagnosed, as well as the choice of tyrosine kinase inhibitor and the plan for surveillance.

It is uncertain if early diagnosis through screening of asymptomatic individuals improves overall survival. Screening could start from the age of 18 years but may be considered at earlier ages depending on the underlying genotype and family history. The long-term benefit of early diagnosis or palliative/prophylactic treatment with tyrosine kinase inhibitors is unknown as there are no data available. Long-term side effects of treatment with imatinib are rare but well documented and could be damaging in patients who have no or minimal disease.

We present the case of a 53-year-old Caucasian patient who was diagnosed with multifocal GIST and subsequently found to be a carrier of a pathogenic germline KIT variant in exon 11. We discuss the implication of treatment and genetic testing in this case and in familial KIT associated GISTs.
Chloroplast Acetyltransferase GNAT2 is Involved in the Organization and Dynamics of Thylakoid Structure
Authors: Rantala Marjaana , Ivanauskaite Aiste , Laihonen Laura , Kanna Sai Divya , Ughy Bettina , Mulo Paula
Published: July 2022

Higher plants acclimate to changes in light conditions by adjusting the thylakoid membrane ultrastructure. Additionally, excitation energy transfer between photosystem II (PSII) and photosystem I (PSI) is balanced in a process known as state transition. These modifications are mediated by reversible phosphorylation of Lhcb1 and Lhcb2 proteins in different pools of light-harvesting complex (LHCII) trimers. Our recent study demonstrated that chloroplast acetyltransferase NUCLEAR SHUTTLE INTERACTING (NSI)/GNAT2 (general control non-repressible 5 (GCN5)-related N-acetyltransferase 2) is also needed for the regulation of light harvesting, evidenced by the inability of the gnat2 mutant to perform state transitions although there are no defects in LHCII phosphorylation. Here, we show that despite contrasting phosphorylation states of LHCII, grana packing in the gnat2 and state transition 7 (stn7) mutants possesses similar features, as the thylakoid structure of the mutants does not respond to the shift from darkness to light, which is in striking contrast to wild type (Wt). Circular dichroism and native polyacrylamide gel electrophoresis analyses further revealed that the thylakoid protein complex organization of gnat2 and stn7 resembles each other, but differ from that of Wt. Also, the location of the phosphorylated Lhcb2 as well as the LHCII antenna within the thylakoid network in gnat2 mutant is different from that of Wt. In gnat2, the LHCII antenna remains largely in grana stacks, where the phosphorylated Lhcb2 is found in all LHCII trimer pools, including those associated with PSII. These results indicate that in addition to phosphorylation-mediated regulation through STN7, the GNAT2 enzyme is involved in the organization and dynamics of thylakoid structure, probably through the regulation of chloroplast protein acetylation.
Reducing Opioid Analgesic Prescribing in Dentistry Through Prescribing Defaults: A Cluster-Randomized Controlled Trial
Authors: Bachhuber Marcus A , Nash Denis , Southern William N , Heo Moonseong , Berger Matthew , Schepis Mark , Sugarman Olivia K , Cunningham Chinazo O
Published: July 2022

Objective

To determine the effect of a uniform, reduced, default dispense quantity for new opioid analgesic prescriptions on the quantity of opioids prescribed in dentistry practices.

Methods

We conducted a cluster-randomized controlled trial within a health system in the Bronx, NY, USA. We randomly assigned three dentistry sites to a 10-tablet default, a 5-tablet default, or no change (control). The primary outcome was the quantity of opioid analgesics prescribed in the new prescription. Secondary outcomes were opioid analgesic reorders and health service utilization within 30 days after the new prescription. We analyzed outcomes from 6 months before implementation through 18 months after implementation.

Results

Overall, 6,309 patients received a new prescription. Compared with the control site, patients at the 10-tablet-default site had a significantly larger change in prescriptions for 10 tablets or fewer (38.7 percentage points; confidence interval [CI]: 11.5 to 66.0), lower number of tablets prescribed (–3.3 tablets; CI: –5.9 to –0.7), and lower morphine milligram equivalents (MME) prescribed (–14.1 MME; CI: –27.8 to –0.4), which persisted in the 30 days after the new prescription despite a higher percentage of reorders (3.3 percentage points; CI: 0.2 to 6.4). Compared with the control site, patients at the 5-tablet-default site did not have a significant difference in any outcomes except for a significantly higher percentage of reorders (2.6 percentage points; CI: 0.2 to 4.9).

Conclusions

Our findings further support the efficacy of strategies that lower default dispense quantities, although they indicate that caution is warranted in the selection of the default.

Trial registration

ClinicalTrials.org ID: NCT03030469.
Unequal policy responsiveness in Spain
Authors: Lupu Noam , Tirado Castro Alejandro
Published: July 2022

Major theories of democratic representation posit that elected officials ought to reflect the preferences of their constituents and act accordingly. But a growing body of research finds that the preferences of the most affluent influence policy outcomes more than those of the least affluent. Yet, broad studies of unequal policy responsiveness have so far only examined Northern Europe and the USA. This biased sample limits our ability both to generalize about unequal responsiveness and to build theories about its causes. We address these limitations by studying Spain, which differs from prior cases in important ways. We collected data from Spanish mass surveys fielded over the period 1976–2016 and researched which of these policies were subsequently approved. We find consistent evidence that policy responsiveness in Spain is unequal. We also find that this pattern holds regardless of the ideology of the government and the type of policy, although with some variation.
Lipidomics of Cell Secretome Combined with the Study of Selected Bioactive Lipids in an In Vitro Model of Osteoarthritis
Authors: Casati Sara , Giannasi Chiara , Niada Stefania , Della Morte Elena , Orioli Marica , Brini Anna T
Published: July 2022

Analytical advancements in lipidomics have enabled large-scale investigations of lipid biology. Herein, we focused on four bioactive lipid families, namely polyunsaturated fatty acids, eicosanoids, endocannabinoids, and N-acylethanolamines, and their involvement in the mesenchymal stem cells (MSC)-related inflammatory scenario. Since MSC secretome may represent a valid therapeutic alternative, here, the complete secretome and its vesicular component from adipose- and bone marrow-derived MSC and dermal fibroblasts were characterized by targeted mass spectrometry lipidomics. The 2-arachidonoylglycerol (2AG) and the palmitoylethanolamide (PEA), previously quantified in the MSC’s secretome, were further investigated by assessing hypothetical effects in an in vitro model of osteoarthritis (OA) based on human primary articular chondrocytes (CH) stimulated with tumor necrosis factor alpha (TNFα). TNFα enhances the release of the inflammatory lipid prostaglandin E2 (PGE2), and an additional increment was observed when CH were treated with both TNFα and 2AG. In contrast, PEA downmodulates the PGE2 release to the levels of unstimulated CH suggesting a protective effect. TNFα also increases the expression of cyclooxygenase 2 (COX2), in particular when combined with 2AG, while PEA partly blunts TNFα-induced COX2 expression. In addition, TNFα-stimulated CH produce significantly higher levels of the inflammatory mediator nitric oxide (NO) both in the presence and in the absence of 2AG, and PEA was able to partially reduce NO release. Our results show a first partial lipidomic profile of MSC and DF secretome and suggest a possible implication of bioactive lipids in the OA scenario and in the future use of these cell-free products as innovative therapeutics.
Antifungal Activity and Possible Mechanism of Bacillus amyloliquefaciens FX2 Against the Postharvest Apple Ring Rot Pathogen
Authors: Li Qi , Hou Zhaoqi , Zhou Dongqin , Jia Mingyun , Lu Shipeng , Yu Jinping
Published: July 2022

Botryosphaeria dothidea-induced apple ring rot is one of the most serious postharvest diseases in apple production. In our preliminary work, we isolated a bacterial strain (FX2) from an infested apple orchard. Here, we confirmed the strong antifungal activity of FX2 on B. dothidea. Through phylogenetic analysis and morphological observations, we identified FX2 as a Bacillus amyloliquefaciens strain. We also found that 10% cell-free supernatant (CFS) of FX2 significantly affected mycelial growth and morphology and almost completely inhibited spore germination and germ tube elongation in B. dothidea. Furthermore, 10% CFS damaged the cell ultrastructure, resulting in a remarkable increase in cellular leakage in B. dothidea mycelia. Thus, CFS has the potential to effectively reduce in vivo B. dothidea infection, reduced lesion diameters to 64.7% compared with the control group, and reduced disease incidence by 15%. Finally, ultrafiltration, desalting chromatography, and anion exchange chromatography showed that the antifungal constituents in CFS are composed mainly of antifungal proteins. We further characterized these potential antifungal proteins via liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Herein, we provide novel insights into the antifungal mechanisms of B. amyloliquefaciens FX2, and we highlight its potential as a novel biocontrol agent for controlling postharvest apple ring rot.
“Finding My Piece in That Puzzle”: A Qualitative Study Exploring How Medical Students at Four U.S. Schools Envision Their Future Professional Identity in Relation to Health Systems
Authors: Leep Hunderfund Andrea N. , Kumbamu Ashok , O’Brien Bridget C. , Starr Stephanie R. , Dekhtyar Michael , Gonzalo Jed D. , Rennke Stephanie , Ridinger Heather , Chang Anna
Published: July 2022

Purpose

Health systems science (HSS) curricula equip future physicians to improve patient, population, and health systems outcomes (i.e., to become “systems citizens”), but the degree to which medical students internalize this conception of the physician role remains unclear. This study aimed to explore how students envision their future professional identity in relation to the system and identify experiences relevant to this aspect of identity formation.

Method

Between December 2018 and September 2019, authors interviewed 48 students at 4 U.S. medical schools with HSS curricula. Semistructured interviews were audiorecorded, transcribed, and analyzed iteratively using inductive thematic analysis. Interview questions explored how students understood the health system, systems-related activities they envisioned as future physicians, and experiences and considerations shaping their perspectives.

Results

Most students anticipated enacting one or more systems-related roles as a future physician, categorized as “bottom-up” efforts enacted at a patient or community level (humanist, connector, steward) or “top-down” efforts enacted at a system or policy level (system improver, system scholar, policy advocate). Corresponding activities included attending to social determinants of health or serving medically underserved populations, connecting patients with team members to address systems-related barriers, stewarding health care resources, conducting quality improvement projects, researching/teaching systems topics, and advocating for policy change. Students attributed systems-related aspirations to experiences beyond HSS curricula (e.g., low-income background; work or volunteer experience; undergraduate studies; exposure to systems challenges affecting patients; supportive classmates, faculty, and institutional culture). Students also described future-oriented considerations promoting or undermining identification with systems-related roles (responsibility, affinity, ability, efficacy, priority, reality, consequences).

Conclusions

This study illuminates systems-related roles medical students at 4 schools with HSS curricula envisioned as part of their future physician identity and highlights past/present experiences and future-oriented considerations shaping identification with such roles. These findings inform practical strategies to support professional identity formation inclusive of systems engagement.
Nonoperative Management of Closed Displaced Tibia Shaft Fractures in Patients Under 18 Years of Age: Low Failure Rate
Authors: Cummings Jason L. , Rivera Asdrubal E. , Pereira Daniel E. , Oladeji Afolayan K. , Landau Andrew J. , Hosseinzadeh Pooya
Published: July 2022

Background:

Tibial shaft fractures are the third most common pediatric long bone fracture pattern. Historically, these fractures have been initially treated with closed reduction and casting (CRC). Recently, there has been an increasing trend toward surgical intervention as an initial treatment for these injuries. In an effort to better understand whether this trend is warranted, this study seeks to characterize the clinical and radiographic outcomes of a large number of children who underwent nonoperative treatment with CRC as their initial treatment for pediatric tibial shaft fractures at a single tertiary care center.

Methods:

Outcomes measured included final alignment, other procedures performed, length of time to full radiographic healing, and length of time in each method of immobilization before progressing to full weight-bearing status. Patients were separated by ages into the following cohorts during statistical analysis: 4 to 8 years, 9 to 12 years, and 13+ years. Differences between continuous variables were analyzed with independent-samples t tests. χ2 tests were used to analyze differences in categorical variables. An α<0.05 was considered statistically significant.

Results:

A total of 137 patients met our inclusion criteria. The median age was 10.19 years (4.03 to 17.43). The average initial displacement among all age groups was 27.42% (±15.05%). After the initial intervention with CRC, all age groups demonstrated an average of <5 degrees of residual angulation and <20% of residual displacement. Complete radiographic healing was seen in 127 (92.7%) patients by 3 months. Loss of reduction requiring additional clinical intervention was seen in 30 (21.9%) patients with only 5% requiring surgical intervention, whereas malunion was seen in a total of 16 (11.7%) patients at the final visit. There were no cases of compartment syndrome or deep wound infection. Male and initial angulation were the only factors predictive of loss of reduction.

Conclusion:

Initial intervention with CRC is a safe and effective treatment for the majority of children in all age groups presenting with tibial shaft fractures demonstrating minimal angulation and displacement with surgical intervention being required in only 5% of patients. Further studies are warranted to elucidate the characteristics of patients who may benefit most from initial surgical intervention.

Level of Evidence:

Level III—retrospective study.
Ultrasound-guided Cervical Retro-laminar Block for Cervical Radicular Pain: A Comparative Analysis
Authors: Khashan Morsi , de Santiago Jesus , Pardo Itai , Regev Gilad , Ophir Dror , Salame Khalil , Lidar Zvi , Brill Silviu , Hochberg Uri
Published: July 2022

Study Design and Objective.

Cervical radiculopathy is a common clinical condition, often treated with cervical epidural steroid injections (ESI). Retro-laminar cervical blocks (RLCB) may be considered safer than ESI as they do not require entering the neuroaxis.

In this study, we evaluated the outcome of RLCB in patients with cervical radiculopathy who had failed conservative treatment and were candidates for cervical spine decompression surgery.

Background Data.

Recently, we reported a clinical pilot study investigating the treatment of cervical radiculopathy with an ultrasound-guided RLCB.

Materials and Methods.

A retrospective, comparative analysis of prospectively collected data was carried out on the medical records of all patients who underwent RLCB for cervical radicular pain, between August 2019 and March 2021.

Results.

Ninety-eight patients were included in the analysis, with a total of 139 procedures.

A significant pain reduction was achieved for most patients immediately after the procedure and at the final follow up (16.9±13.4 wk). The mean numerical rating scale for the whole cohort changed from 7.21±2.51 to 4.04±2.51 (P-value <0.01) at the time of discharge, with similar patterns at the subgroup level. A functional evaluation was carried out by a questionnaire (Neck Disability Index—NDI). Overall, 83% of patients had a lower postprocedural NDI than preprocedural NDI. For 80% of patients, the improvement of NDI surpassed the minimal clinically important change at the final assessment. Most patients (61%) were discharged after just one RLCB. Eight patients (8%) eventually underwent surgery. The most frequent complaint was injection site soreness; however, there were no major adverse events reported.

Conclusions.

These findings suggest that RLCB can be performed as an alternative to cervical ESI and decompressive surgery in patients with cervical radicular pain that’s refractory to noninvasive treatment. More comparative and prospective studies are needed to confirm our results.
Reoperation for Misplaced Pedicle Screws: A Multicenter Retrospective Study
Authors: Odate Seiichi , Fujibayashi Shunsuke , Otsuki Bungo , Shikata Jitsuhiko , Tsubouchi Naoya , Tsutsumi Ryosuke , Ota Masato , Yusuke Kanba , Kimura Hiroaki , Onishi Eijiro , Tanida Shimei , Ito Hideo , Ishibe Tatsuya , Matsuda Shuichi
Published: July 2022

Study Design.

A multicenter retrospective analysis

Objective.

To investigate reoperation of misplaced pedicle screws (MPSs) after posterior spinal fusion (PSF), focusing on neurological complications.

Summary of Background Data.

The management strategy for MPSs and the clinical results after reoperation are poorly defined.

Methods.

Subjects were 10,754 patients (73,777 pedicle screws) who underwent PSF at 11 hospitals over 15 years. The total number of reoperations for MPS and patient clinical data were obtained from medical records at each hospital.

Results.

The rate of reoperation for screw misplacement per screw was 0.17%. A total of 69 patients (mean age, 67.4±16.5 y) underwent reoperation because of 82 MPS. Reasons for reoperation were neurological symptoms (58 patients), contact with vessels (5), suboptimal bone purchase (4), and misplacement recognized during operation (2). Neurological symptoms were the major reason for reoperation in cervical (5/5 screws, 100%) and lumbo-sacral (60/67 screws, 89.6%) regions. Contact with vessels was the major reason for reoperation in the thoracic spine (6/10 screws, 60.0%). We further evaluated 60 MPSs in the lumbo-sacrum necessitating reoperation because of neurological symptoms. The majority of MPSs necessitating reoperation were placed in the lower lumbar spine (43/60 screws, 71.7%). The mean pedicle breach tended to be larger in the incomplete recovery group than in the complete recovery group (6.8±2.4 mm vs. 5.9±2.2 mm, P=0.146), and the cutoff value resulting in incomplete resolution was 5.0 mm. Multivariate analysis revealed that medial-caudal breaches (vs. medial breach, OR 25.8, 95%CI 2.58-258, P=0.0057) and sensory and motor disturbances (vs. sensory only, OR 8.57, 95%CI 1.30-56.6, P=0.026) were significant factors for incomplete resolution of neurological symptoms.

Conclusions.

After reoperation, 70.1% of the patients acquired complete resolution of neurological symptoms. Features of possible residual neurological symptoms were sensory and motor disturbance, medial-caudal breach, and larger pedicle breach (>5 mm).
Complications, Readmissions, Revisions, and Patient-reported Outcomes in Patients With Parkinson Disease Undergoing Elective Spine Surgery: A Propensity-matched Analysis
Authors: Steinle Anthony M. , Nian Hui , Pennings Jacquelyn S. , Bydon Mohamad , Asher Anthony , Archer Kristin R. , Gardocki Raymond J. , Zuckerman Scott L. , Stephens Byron F. , Abtahi Amir M.
Published: July 2022

Study Design.

Retrospective analysis on prospectively collected data.

Objective.

To determine the effectiveness of elective spine surgery in patients with Parkinson disease (PD).

Background Context.

PD has become increasingly prevalent in an aging population. While surgical treatment for degenerative spine pathology is often required in this population, previous literature has provided mixed results regarding its effectiveness.

Methods.

Data from the Quality Outcomes Database (QOD) was queried between April 2013 and January 2019. Three surgical groups were identified: (1) elective lumbar surgery, (2) elective cervical surgery for myelopathy, (3) elective cervical surgery for radiculopathy. Patients without PD were propensity matched against patients with PD in a 5:1 ratio without replacement based on American Society of Anesthesiology grade, arthrodesis, surgical approach, number of operated levels, age, and baseline Oswestry Disability Index, Numerical Rating Scale (NRS) extremity pain, NRS back pain, and EuroQol 5-Dimensions (EQ-5D). The mean difference was calculated for continuous outcomes (Oswestry Disability Index, NRS leg pain, NRS back pain, and EQ-5D at 3 and 12 mo after surgery) and the risk difference was calculated for binary outcomes (patient satisfaction, complications, readmission, reoperation, and mortality).

Results.

For the lumbar analysis, PD patients had a higher rate of reoperation at 12 months (risk difference=0.057, P=0.015) and lower mean EQ-5D score at 12 months (mean difference=−0.053, P=0.005) when compared with patients without PD. For the cervical myelopathy cohort, PD patients had lower NRS neck pain scores at 3 months (mean difference=−0.829, P=0.005) and lower patient satisfaction at 3 months (risk difference=−0.262, P=0.041) compared with patients without PD. For the cervical radiculopathy cohort, PD patients demonstrated a lower readmission rate at 3 months (risk difference=−0.045, P=0.014) compared with patients without PD.

Conclusion.

For the matched analysis, in general, patients with and without PD had similar patient-reported outcomes and complication, readmission, and reoperation rates. These results demonstrate that a diagnosis of PD alone should not represent a major contraindication to elective spine surgery.
Risk factors for CMV infection within 100 days posttransplantation in patients with acute leukemia
Authors: Chen Juan , Pang Aiming , Zhao Yuanqi , Liu Li , Ma Runzhi , Wei Jialin , Chen Xin , He Yi , Yang Donglin , Zhang Rongli , Zhai Weihua , Ma Qiaoling , Jiang Erlie , Han Mingzhe , Zhou Jiaxi , Feng Sizhou
Published: July 2022

Objective:

To investigate the risk factors for cytomegalovirus (CMV) infection within 100 days and the relationship between early CMV infection and 1-year relapse for patients with acute leukemia following allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods:

Three hundred fifty-nine patients with acute leukemia who received allo-HSCT at our center between January 2015 and January 2020 were retrospectively reviewed.

Results:

Of 359 patients, 48.19% (173) patients experienced CMV infection within 100 days posttransplantation. In univariate and multivariate logistic analysis, haploidentical-related donor (HRD) (P < 0.001; odds ratio [OR], 5.542; 95% confidence interval [CI], 3.186–9.639), and ratio of CD3+CD8+ cells in lymphocytes <14.825% (P < 0.001; OR, 3.005; 95% CI, 1.712–5.275) were identified as 2 independent risk factors. One-year relapse rate (RR) between the CMV infection group and the non-CMV infection group was not statistically significant (18.5% vs 19.9%, P = 0.688). When we divided the total cohort into AML, ALL, and MAL subgroups, there were no significant differences as well (P = 0.138; P = 0.588; P = 0.117; respectively).

Conclusion:

In conclusion, donor type (HRD) and the insufficient recovery of CD3+CD8+ cells were independent risk factors for CMV infection within 100 days posttransplantation in patients with acute leukemia. CMV infection within 100 days did not influence the incidence of relapse in 1 year for patients with acute leukemia.