bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of comprehensive rehabilitation in the care of degenerative cervical myelopathy
Authors: Catz Amiram , Watts Yaron , Amir Hagay , Front Lilach , Gelernter Ilana , Michaeli Dianne , Bluvshtein Vadim , Aidinoff Elena 
Published: March 2024

Abstract
Study design
Retrospective cohort study.

Objective
To find out if comprehensive rehabilitation itself can improve daily performance in persons with DCM.

Setting
The spinal department of a rehabilitation hospital.

Methods
Data from 116 DCM inpatients who underwent comprehensive rehabilitation after spinal surgery were retrospectively analyzed. The definitions of the calculated outcome variables made possible analyses that distinguished the effect of rehabilitation from that of spinal surgery. Paired t-tests were used to compare admission with discharge outcomes and functional gains. Spearman’s correlations were used to assess relationships between performance gain during rehabilitation and between time from surgery to rehabilitation.

Results
The Spinal Cord Injury Ability Realization Measurement Index (SCI-ARMI) increased during rehabilitation from 57 (24) to 78 (19) (p < 0.001). The Spinal Cord Independence Measure 3rd version (SCIM III) gain attributed to neurological improvement (dSCIM-IIIn) was 6.3 (9.2), and that attributed to rehabilitation (dSCIM-IIIr) 16 (18.5) (p < 0.001). dSCIM-IIIr showed a rather weak negative correlation with time from spinal surgery to rehabilitation (r = −0.42, p < 0.001).

Conclusions
The study showed, for the first time, that comprehensive rehabilitation can achieve considerable functional improvement for persons with DCM of any degree, beyond that of spinal surgery. Combined with previously published evidence, this indicates that comprehensive rehabilitation can be considered for persons with DCM of any functional degree, before surgery.
Pharmacogenetic and clinical risk factors for bevacizumab-related gastrointestinal hemorrhage in prostate cancer patients treated on CALGB 90401 (Alliance)
Authors: Patel Jai N. , Jiang Chen , Owzar Kouros , Hertz Daniel L. , Wang Janey , Mulkey Flora A. , Kelly William K. , Halabi Susan , Furukawa Yoichi , Lassiter Cameron , Dorsey Susan G. , Friedman Paula N. , Small Eric J. , Carducci Michael A. , Kelley Michael J. , Nakamura Yusuke , Kubo Michiaki , Ratain Mark J. , Morris Michael J. , McLeod Howard L. 
Published: March 2024

AbstractThe objective of this study was to discover clinical and pharmacogenetic factors associated with bevacizumab-related gastrointestinal hemorrhage in Cancer and Leukemia Group B (Alliance) 90401. Patients with metastatic castration-resistant prostate cancer received docetaxel and prednisone ± bevacizumab. Patients were genotyped using Illumina HumanHap610-Quad and assessed using cause-specific risk for association between single nucleotide polymorphisms (SNPs) and gastrointestinal hemorrhage. In 1008 patients, grade 2 or higher gastrointestinal hemorrhage occurred in 9.5% and 3.8% of bevacizumab (n = 503) and placebo (n = 505) treated patients, respectively. Bevacizumab (P < 0.001) and age (P = 0.002) were associated with gastrointestinal hemorrhage. In 616 genetically estimated Europeans (n = 314 bevacizumab and n = 302 placebo treated patients), grade 2 or higher gastrointestinal hemorrhage occurred in 9.6% and 2.0% of patients, respectively. One SNP (rs1478947; HR 6.26; 95% CI 3.19–12.28; P = 9.40 × 10−8) surpassed Bonferroni-corrected significance. Grade 2 or higher gastrointestinal hemorrhage rate was 33.3% and 6.2% in bevacizumab-treated patients with the AA/AG and GG genotypes, versus 2.9% and 1.9% in the placebo arm, respectively. Prospective validation of these findings and functional analyses are needed to better understand the genetic contribution to treatment-related gastrointestinal hemorrhage.
Hematopoietic cell transplantation and cellular therapies in Europe 2022. CAR-T activity continues to grow; transplant activity has slowed: a report from the EBMT
Authors: Passweg Jakob R. , Baldomero Helen , Ciceri Fabio , de la Cámara Rafael , Glass Bertram , Greco Raffaella , Hazenberg Mette D. , Kalwak Krzysztof , McLornan Donal P. , Neven Bénédicte , Perić Zinaida , Risitano Antonio M. , Ruggeri Annalisa , Snowden John A. , Sureda Anna 
Published: March 2024

AbstractIn 2022, 46,143 HCT (19,011 (41.2%) allogeneic and 27,132 (58.8%) autologous) in 41,854 patients were reported by 689 European centers. 4329 patients received advanced cellular therapies, 3205 of which were CAR-T. An additional 2854 patients received DLI. Changes compared to the previous year were an increase in CAR-T treatments (+27%) and decrease in allogeneic (−4.0%) and autologous HCT (−1.7%). Main indications for allogeneic HCT were myeloid malignancies (10,433; 58.4%), lymphoid malignancies (4,674; 26.2%) and non-malignant disorders (2572; 14.4%). Main indications for autologous HCT were lymphomas (7897; 32.9%), PCD (13,694; 57.1%) and solid tumors (1593; 6.6%). In allogeneic HCT, use of sibling donors decreased by −7.7%, haploidentical donors by −6.3% and unrelated donors by −0.9%. Overall cord blood HCT decreased by −16.0%. Use of allogeneic, and to a lesser degree autologous HCT, decreased for lymphoid malignancies likely reflecting availability of new treatment modalities, including small molecules, bispecific antibodies, and CAR-T cells. Pediatric HCT activity remains stable (+0.3%) with differences between allogeneic and autologous HCT. Use of CAR-T continues to increase and reached a cumulative total of 9039 patients treated with wide differences across European countries. After many years of continuous growth, increase in application of HCT seems to have slowed down.
Somatic CAG repeat instability in intermediate alleles of the HTT gene and its potential association with a clinical phenotype
Authors: Ruiz de Sabando Ainara , Ciosi Marc , Galbete Arkaitz , Cumming Sarah A. ,   Spanish HD Collaborative Group, Álvarez Victoria , Martinez-Descals Asunción , Mila Montserrat , Trujillo-Tiebas Maria José , López-Sendón Jose Luis , Fenollar-Cortés María , Legarda Inés , Bernal Noguera Sara , Millán Jose M. , Durán-Herrera Camen , Ruiz-Martínez Javier , Ruiz Onandi Rebeca , Monckton Darren G. , Ramos-Arroyo Maria A. 
Published: March 2024

AbstractHuntington disease (HD) is a neurodegenerative disorder caused by ≥36 CAGs in the HTT gene. Intermediate alleles (IAs) (27–35 CAGs) are not considered HD-causing, but their potential association with neurocognitive symptoms remains controversial. As HTT somatic CAG expansion influences HD onset, we hypothesised that IAs are somatically unstable, and that somatic CAG expansion may drive phenotypic presentation in some IA carriers. We quantified HTT somatic CAG expansions by MiSeq sequencing in the blood DNA of 164 HD subjects and 191 IA (symptomatic and control) carriers, and in the brain DNA of a symptomatic 33 CAG carrier. We also performed genotype-phenotype analysis. The phenotype of symptomatic IA carriers was characterised by motor (85%), cognitive (27%) and/or behavioural (29%) signs, with a late (58.7 ± 18.6 years), but not CAG-dependent, age at onset. IAs displayed somatic expansion that were CAG and age-dependent in blood DNA, with 0.4% and 0.01% of DNA molecules expanding by CAG and year, respectively. Somatic expansions of +1 and +2 CAGs were detected in the brain of the individual with 33 CAGs, with the highest expansion frequency in the putamen (10.3%) and the lowest in the cerebellum (4.8%). Somatic expansion in blood DNA was not different in symptomatic vs. control IA carriers. In conclusion, we show that HTT IAs are somatically unstable, but we found no association with HD-like phenotypes. It is plausible, however, that some IAs, close to the HD pathological threshold and with a predisposing genetic background, could manifest with neurocognitive symptoms.
The inclusion of Amazon mangroves in Brazil’s REDD+ program
Authors: Bernardino Angelo F. , Mazzuco Ana Carolina A. , Costa Rodolfo F. , Souza Fernanda , Owuor Margaret A. , Nobrega Gabriel N. , Sanders Christian J. , Ferreira Tiago O. , Kauffman J. Boone 
Published: March 2024

AbstractThe Legal Amazon of Brazil holds vast mangrove forests, but a lack of awareness of their value has prevented their inclusion into results-based payments established by the United Nations Framework Convention on Climate Change. Based on an inventory from over 190 forest plots in Amazon mangroves, we estimate total ecosystem carbon stocks of 468 ± 67 Megagrams (Mg) ha−1; which are significantly higher than Brazilian upland biomes currently included into national carbon offset financing. Conversion of mangroves results in potential emissions of 1228 Mg CO2e ha−1, which are 3-fold higher than land use emissions from conversion of the Amazon rainforest. Our work provides the foundation for the inclusion of mangroves in Brazil’s intended Nationally Determined Contribution, and here we show that halting mangrove deforestation in the Legal Amazon would generate avoided emissions of 0.9 ± 0.3 Teragrams (Tg) CO2e yr−1; which is equivalent to the annual carbon accumulation in 82,400 ha of secondary forests.
Inactivation of cytidine triphosphate synthase 1 prevents fatal auto-immunity in mice
Authors: Soudais Claire , Schaus Romane , Bachelet Camille , Minet Norbert , Mouasni Sara , Garcin Cécile , Souza Caique Lopes , David Pierre , Cousu Clara , Asnagli Hélène , Parker Andrew , Palmquist-Gomes Paul , Sepulveda Fernando E. , Storck Sébastien , Meilhac Sigolène M. , Fischer Alain , Martin Emmanuel , Latour Sylvain 
Published: March 2024

AbstractDe novo synthesis of the pyrimidine, cytidine triphosphate (CTP), is crucial for DNA/RNA metabolism and depends on the CTP synthetases, CTPS1 and −2. Partial CTPS1 deficiency in humans has previously been shown to lead to immunodeficiency, with impaired expansion of T and B cells. Here, we examine the effects of conditional and inducible inactivation of Ctps1 and/or Ctps2 on mouse embryonic development and immunity. We report that deletion of Ctps1, but not Ctps2, is embryonic-lethal. Tissue and cells with high proliferation and renewal rates, such as intestinal epithelium, erythroid and thymic lineages, activated B and T lymphocytes, and memory T cells strongly rely on CTPS1 for their maintenance and growth. However, both CTPS1 and CTPS2 are required for T cell proliferation following TCR stimulation. Deletion of Ctps1 in T cells or treatment with a CTPS1 inhibitor rescued Foxp3-deficient mice from fatal systemic autoimmunity and reduced the severity of experimental autoimmune encephalomyelitis. These findings support that CTPS1 may represent a target for immune suppression.
A humanized mouse model for adeno-associated viral gene therapy
Authors: Barzi Mercedes , Chen Tong , Gonzalez Trevor J. , Pankowicz Francis P. , Oh Seh Hoon , Streff Helen L. , Rosales Alan , Ma Yunhan , Collias Sabrina , Woodfield Sarah E. , Diehl Anna Mae , Vasudevan Sanjeev A. , Galvan Thao N. , Goss John , Gersbach Charles A. , Bissig-Choisat Beatrice , Asokan Aravind , Bissig Karl-Dimiter 
Published: March 2024

AbstractClinical translation of AAV-mediated gene therapy requires preclinical development across different experimental models, often confounded by variable transduction efficiency. Here, we describe a human liver chimeric transgene-free Il2rg−/−/Rag2−/−/Fah−/−/Aavr−/− (TIRFA) mouse model overcoming this translational roadblock, by combining liver humanization with AAV receptor (AAVR) ablation, rendering murine cells impermissive to AAV transduction. Using human liver chimeric TIRFA mice, we demonstrate increased transduction of clinically used AAV serotypes in primary human hepatocytes compared to humanized mice with wild-type AAVR. Further, we demonstrate AAV transduction in human teratoma-derived primary cells and liver cancer tissue, displaying the versatility of the humanized TIRFA mouse. From a mechanistic perspective, our results support the notion that AAVR functions as both an entry receptor and an intracellular receptor essential for transduction. The TIRFA mouse should allow prediction of AAV gene transfer efficiency and the study of AAV vector biology in a preclinical human setting.
Prediction of highly stable 2D carbon allotropes based on azulenoid kekulene
Authors: Zhang Zhenzhe , Pham Hanh D. M. , Perepichka Dmytro F. , Khaliullin Rustam Z. 
Published: March 2024

AbstractDespite enormous interest in two-dimensional (2D) carbon allotropes, discovering stable 2D carbon structures with practically useful electronic properties presents a significant challenge. Computational modeling in this work shows that fusing azulene-derived macrocycles – azulenoid kekulenes (AK) – into graphene leads to the most stable 2D carbon allotropes reported to date, excluding graphene. Density functional theory predicts that placing the AK units in appropriate relative positions in the graphene lattice opens the 0.54 eV electronic bandgap and leads to the appearance of the remarkable 0.80 eV secondary gap between conduction bands – a feature that is rare in 2D carbon allotropes but is known to enhance light absorption and emission in 3D semiconductors. Among porous AK structures, one material stands out as a stable narrow-multigap (0.36 and 0.56 eV) semiconductor with light charge carriers (me = 0.17 m0,  mh = 0.19 m0), whereas its boron nitride analog is a wide-multigap (1.51 and 0.82 eV) semiconductor with light carriers (me = 0.39 m0,  mh = 0.32 m0). The multigap engineering strategy proposed here can be applied to other carbon nanostructures creating novel 2D materials for electronic and optoelectronic applications.
PsAF5 functions as an essential adapter for PsPHB2-mediated mitophagy under ROS stress in Phytophthora sojae
Authors: Li Wenhao , Zhu Hongwei , Chen Jinzhu , Ru Binglu , Peng Qin , Miao Jianqiang , Liu Xili 
Published: March 2024

AbstractHost-derived reactive oxygen species (ROS) are an important defense means to protect against pathogens. Although mitochondria are the main intracellular targets of ROS, how pathogens regulate mitochondrial physiology in response to oxidative stress remains elusive. Prohibitin 2 (PHB2) is an inner mitochondrial membrane (IMM) protein, recognized as a mitophagy receptor in animals and fungi. Here, we find that an ANK and FYVE domain-containing protein PsAF5, is an adapter of PsPHB2, interacting with PsATG8 under ROS stress. Unlike animal PHB2 that can recruit ATG8 directly to mitochondria, PsPHB2 inPhytophthora sojaecannot recruit PsATG8 to stressed mitochondria without PsAF5.PsAF5deletion impairs mitophagy under ROS stress and increases the pathogen’s sensitivity to H2O2, resulting in the attenuation ofP. sojaevirulence. This discovery of a PsPHB2-PsATG8 adapter (PsAF5) in plant-pathogenic oomycetes reveals that mitophagy induction by IMM proteins is conserved in eukaryotes, but with differences in the details of ATG8 recruitment.
A coarse-grained bacterial cell model for resource-aware analysis and design of synthetic gene circuits
Authors: Sechkar Kirill , Steel Harrison , Perrino Giansimone , Stan Guy-Bart 
Published: March 2024

AbstractWithin a cell, synthetic and native genes compete for expression machinery, influencing cellular process dynamics through resource couplings. Models that simplify competitive resource binding kinetics can guide the design of strategies for countering these couplings. However, in bacteria resource availability and cell growth rate are interlinked, which complicates resource-aware biocircuit design. Capturing this interdependence requires coarse-grained bacterial cell models that balance accurate representation of metabolic regulation against simplicity and interpretability. We propose a coarse-grained E. coli cell model that combines the ease of simplified resource coupling analysis with appreciation of bacterial growth regulation mechanisms and the processes relevant for biocircuit design. Reliably capturing known growth phenomena, it provides a unifying explanation to disparate empirical relations between growth and synthetic gene expression. Considering a biomolecular controller that makes cell-wide ribosome availability robust to perturbations, we showcase our model’s usefulness in numerically prototyping biocircuits and deriving analytical relations for design guidance.
The search for CDK4/6 inhibitor biomarkers has been hampered by inappropriate proliferation assays
Authors: Foy Reece , Lew Kah Xin , Saurin Adrian T. 
Published: March 2024

AbstractCDK4/6 inhibitors are effective at treating advanced HR+ /HER2- breast cancer, however biomarkers that can predict response are urgently needed. We demonstrate here that previous large-scale screens designed to identify which tumour types or genotypes are most sensitive to CDK4/6 inhibitors have misrepresented the responsive cell lines because of a reliance on metabolic proliferation assays. CDK4/6-inhibited cells arrest in G1 but continue to grow in size, thereby producing more mitochondria. We show that this growth obscures the arrest using ATP-based proliferation assays but not if DNA-based assays are used instead. Furthermore, lymphoma lines, previously identified as the most sensitive, simply appear to respond the best using ATP-based assays because they fail to overgrow during the G1 arrest. Similarly, the CDK4/6 inhibitor abemaciclib appears to inhibit proliferation better than palbociclib because it also restricts cellular overgrowth through off-target effects. DepMap analysis of screening data using reliable assay types, demonstrates that palbociclib-sensitive cell types are also sensitive to Cyclin D1, CDK4 and CDK6 knockout/knockdown, whereas the palbociclib-resistant lines are sensitive to Cyclin E1, CDK2 and SKP2 knockout/knockdown. Potential biomarkers of palbociclib-sensitive cells are increased expression of CCND1 and RB1, and reduced expression of CCNE1 and CDKN2A. Probing DepMap with similar data from metabolic assays fails to reveal these associations. Together, this demonstrates why CDK4/6 inhibitors, and any other anti-cancer drugs that arrest the cell cycle but permit continued cell growth, must now be re-screened against a wide-range of cell types using an appropriate proliferation assay. This would help to better inform clinical trials and to identify much needed biomarkers of response.
Acute and short-term fluctuations in gravity are associated with changes in circulatory plasma protein levels
Authors: Lang Alexander , Binneboessel Stephan , Nienhaus Fabian , Bruno Raphael Romano , Wolff Georg , Piayda Kerstin , Pfeiler Susanne , Ezzahoini Hakima , Oehler Daniel , Kelm Malte , Winkels Holger , Gerdes Norbert , Jung Christian 
Published: March 2024

AbstractGravitational changes between micro- and hypergravity cause several adaptations and alterations in the human body. Besides muscular atrophy and immune system impairment, effects on the circulatory system have been described, which can be associated with a wide range of blood biomarker changes. This study examined nine individuals (seven males, two females) during a parabolic flight campaign (PFC). Thirty-one parabolas were performed in one flight day, resulting in ~22 s of microgravity during each parabola. Each participant was subjected to a single flight day with a total of 31 parabolas, totaling 11 min of microgravity during one parabolic flight. Before and after (1 hour (h) and 24 h), the flights blood was sampled to examine potential gravity-induced changes of circulating plasma proteins. Proximity Extension Assay (PEA) offers a proteomic solution, enabling the simultaneous analysis of a wide variety of plasma proteins. From 2925 unique proteins analyzed, 251 (8.58%) proteins demonstrated a differential regulation between baseline, 1 h and 24 h post flight. Pathway analysis indicated that parabolic flights led to altered levels of proteins associated with vesicle organization and apoptosis up to 24 h post microgravity exposure. Varying gravity conditions are associated with poorly understood physiological changes, including stress responses and fluid shifts. We provide a publicly available library of gravity-modulated circulating protein levels illustrating numerous changes in cellular pathways relevant for inter-organ function and communication.
A register and questionnaire study of long-term general health symptoms following SARS-CoV-2 vaccination in Denmark
Authors: O’Regan Elisabeth , Svalgaard Ingrid Bech , Sørensen Anna Irene Vedel , Spiliopoulos Lampros , Bager Peter , Nielsen Nete Munk , Hansen Jørgen Vinsløv , Koch Anders , Meder Inger Kristine , Videbech Poul , Ethelberg Steen , Hviid Anders 
Published: March 2024

AbstractMany individuals who refuse COVID-19 vaccination have concerns about long-term side effects. Here, we report findings on self-reported symptoms from a Danish survey- and register study. The study included 34,868 vaccinated primary course recipients, 95.8% of whom received mRNA vaccines, and 1,568 unvaccinated individuals. Participants had no known history of SARS-CoV-2 infection. Using g-computation on logistic regression, risk differences (RDs) for symptoms between vaccinated and unvaccinated persons were estimated with adjustments for possible confounders. Within six weeks after vaccination, higher risks were observed for physical exhaustion (RD 4.9%, 95% CI 1.1% to 8.4%), fever or chills (RD 4.4%, 95% CI 2.1% to 6.7%), and muscle/joint pain (RD 7.0%, 95% CI 3.1% to 10.7%), compared to unvaccinated individuals. Beyond twenty-six weeks, risks were higher among the vaccinated for sleeping problems (RD 3.0, 95% 0.2 to 5.8), fever or chills (RD 2.0, 95% CI 0.4 to 3.6), reduced/altered taste (RD 1.2, 95% CI 0.2 to 2.3) and shortness of breath (RD 2.6, 95% CI 0.9 to 4.0). However, when examining pre-omicron responses only, the difference for reduced/altered taste was significant. As expected, the risk of experiencing physical exhaustion, fever or chills, and muscle/joint pain was higher among persons who responded within six weeks of completing the primary course. No significant differences were observed for the 7-25-week period after vaccination. Associations for the period beyond 26 weeks must be interpreted with caution and in the context of undetected SARS-CoV-2 infection, wide confidence intervals, and multiple testing. Overall, we observe no concerning signs of long-term self-reported physical, cognitive, or fatigue symptoms after vaccination.
Phage proteins target and co-opt host ribosomes immediately upon infection
Authors: Gerovac Milan , Chihara Kotaro , Wicke Laura , Böttcher Bettina , Lavigne Rob , Vogel Jörg 
Published: March 2024

AbstractBacteriophages must seize control of the host gene expression machinery to replicate. To bypass bacterial anti-phage defence systems, this host takeover occurs immediately upon infection. A general understanding of phage mechanisms for immediate targeting of host transcription and translation processes is lacking. Here we introduce an integrative high-throughput approach to uncover phage-encoded proteins that target the gene expression machinery of Pseudomonas aeruginosa immediately upon infection with the jumbo phage ΦKZ. By integrating biochemical, genetic and structural analyses, we identify an abundant and conserved phage factor ΦKZ014 that targets the large ribosomal subunit by binding the 5S ribosomal RNA, and rapidly promotes replication in several clinical isolates. ΦKZ014 is among the earliest ΦKZ proteins expressed after infection and remains bound to ribosomes during the entire translation cycle. Our study provides a strategy to decipher molecular components of phage-mediated host takeover and argues that phage genomes represent an untapped discovery space for proteins that modulate the host gene expression machinery.