bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ablative Treatment of Inflammatory and Other Diseases With Monoclonal Antibodies (Mabs) or Janus Kinases (Nibs) Increases Risk for Infection
Authors: Santana Eric , Rosenthal Ken S. 
Published: October 2023

Abstract
Monoclonal antibodies (mabs) and small molecule Janus kinase (JAK) inhibitors (nibs) are useful for treating inflammatory disease, autoimmune disease, and tumors, especially leukemia. Inhibition or depletion of the cytokines or cells with these drugs can result in loss of important protection against certain microbial infections. Recurrences of tuberculosis, hepatitis B and C, and zoster are especially sensitive to immune depletion. The consequences of inhibition of cytokines, molecules, pathways and cells by these drugs are described, depicted, and tabulated.
Efficacy of rehabilitation after provision of ICRC lower limb prostheses in low-income and middle-income countries: A quantitative assessment from Myanmar
Authors: Weerasinghe Stephney , Aranceta-Garza Alejandra , Murray Laura 
Published: October 2023

Background:
Low-income and middle-income countries (LMICs) have poorly resourced health services. Lack of access to assistive devices, such as prosthetics, may limit the functional outcomes of persons with amputation and affect quality of life (QoL).

Objective:
The objective of this study was to assess the functional level and QoL of prosthetic users in LMICs when prescribed a prosthesis made from International Committee for Red Cross (ICRC) components.

Study design:
The study design included a quantitative descriptive methodology assessing functional outcomes and QoL after prosthetic provision.

Methods:
Participants were identified from the prosthetic service in Mandalay, Myanmar. Included participants were those with unilateral, traumatic, lower limb amputations, with ICRC devices delivered at least 6 months earlier. Participants attended the prosthetic service and were assessed using the Amputee Mobility Predictor with Prosthesis tool and the World Health Organization Quality of Life Brief and Disability modules.

Results:
Thirty-five participants completed the study; of them, 63% were persons with transtibial level amputation and 37% were with transfemoral level amputation. Approximately 83% achieved a score of more than 37 using the Amputee Mobility Predictor with Prosthesis. There is a strong positive correlation between QoL and physical health (r = 0.55; p < 0.001), social relationships (r = 0.66; p < 0.001), and inclusion (r = 0.53; p < 0.001). Participants had a better QoL and overall health when they had better psychological health.

Conclusion:
The patient-based results presented within this study could be considered as a contribution to the evidence base and importance of provision of prosthetic services in LMICs. It was observed that participants with an amputation were able to achieve a high level of physical function with the ICRC prostheses while also reporting a high QoL.
ASSOCIATION BETWEEN PLASMA TRANSFUSION AND IN-HOSPITAL MORTALITY IN CRITICALLY ILL PATIENTS WITH SEPSIS-INDUCED COAGULOPATHY
Authors: Wang Renli , Liu Rongjun , Xu Zhaojun 
Published: October 2023

ABSTRACT

Background: Plasma is commonly used in patients with coagulopathy; however, its role in patients with sepsis-induced coagulopathy (SIC) is unclear. This study aimed to evaluate the effect of plasma transfusion on the prognosis of patients with SIC. Methods: Data were collected from the Medical Information Mart for Intensive Care IV database. Multivariable logistic regression analysis was used to determine the association between plasma transfusion and the incidence of in-hospital mortality, pulmonary embolism, and lower extremity deep vein thrombosis in critically ill patients with SIC. Propensity score matching (PSM) and propensity score–based inverse probability of treatment weighting (IPTW) models were used to ensure the robustness of our findings. Furthermore, the nonparametric relationship between in-hospital mortality and plasma transfusion volume was analyzed using restricted cubic spline. Subgroups analyses were performed for age, sex, Charlson score, Sequential Organ Failure Assessment score, SIC score, and with hemorrhage. Results: A total of 8,747 patients with SIC were enrolled: of them, 1874 were in the plasma infusion group, and 6,873 were in the no plasma infusion group. Compared with the no plasma infusion group, the plasma infusion group had higher in-hospital mortality (odds ratio [OR], 1.4411; 95% confidence interval [CI], 1.2280–1.6897, P < 0.05), and the results were robust after PSM (OR, 1.3227; 95% CI, 1.1152–1.5697; P < 0.05) and IPTW (OR, 1.1541; 95% CI, 1.0738–1.2404; P < 0.05). Similar results were also observed in different subgroups. However, because of conflicting results after PSM and IPTW, we were unable to definitively link plasma transfusion with pulmonary embolism and deep vein thrombosis. Compared with the no early plasma transfusion group (≥12 h), the in-hospital mortality rate was lower in the early plasma transfusion group (<12 h) (OR, 0.5426; 95% CI, 0.4398–0.6844; P < 0.05). The restricted cubic spline analysis indicated that increased plasma transfusion was associated with increased in-hospital mortality in patients with SIC. Conclusion: Plasma transfusion increases in-hospital mortality in patients with SIC, and the mortality rate increases with the amount of plasma transfusion. Patients with SIC who received early plasma infusion had lower in-hospital mortality than those who received no early plasma transfusion.
Improving the Access of Highly Sensitized Patients to Kidney Transplantation From Deceased Donors: The Spanish PATHI Program With Allocation Based on the Virtual Crossmatch
Authors: Valentin Maria O. , Crespo Marta , Fernandez Constantino , Muro Manuel , Vega Rocio , Palou Eduard , Ruiz Juan Carlos , Diekman Fritz , Padilla Maria , Mancebo Esther , Perez Isabel , Andres Amado , Ontañon Jesus , Dominguez-Gil Beatriz ,   on behalf of the Working Group PATHI
Published: October 2023

Background.
In 2015, the Spanish National Transplant Organization developed a prioritization system (Program for Access to Transplantation for Highly Sensitized Patients [PATHI]) to increase transplant options for patients with calculated panel-reactive antibodies (cPRAs) ≥98%, based on virtual crossmatch. We describe the experience with the implementation of PATHI and assess its efficacy.

Methods.
PATHI registry was used to collect characteristics of donors and patients between June 15, 2015, and March 1, 2018. One-year graft and patient survival and acute rejection were also measured. A Cox model was used to identify factors related to patient death and graft loss and logistical regression for those associated with rejection.

Results.
One thousand eighty-nine patients were included, and 272 (25%) were transplanted. Transplant rate by cPRA was 54.9%, 40.5%, and 12.8% in patients with cPRA98%, cPRA99%, and cPRA100%, respectively. One-year patient survival was 92.5%. Recipient age ≥60, time under dialysis >7 y, and delayed graft function were mortality risk factors. One-year graft survival was 88.7%. The factor related to graft loss was delayed graft function. The rejection rate was 22%. Factors related to rejection were sex, older recipients, and posttransplant donor-specific antibodies.

Conclusions.
A prioritization approach increases transplant options for highly sensitized patients with appropriate short-term postransplant outcomes. Along with other programs, PATHI may inspire other countries to adopt strategies to meet transplant needs of these patients.
Long-Term Outcomes and Predictors of Response in Breast Cancer Patients with Advanced Nodal Involvement
Authors: Sun Susie X , Piotrowski Matthew J , Adesoye Taiwo , Mitchell Melissa P , Garber Haven R , Teshome Mediget , Kuerer Henry M , Tamirisa Nina , Singh Puneet 
Published: October 2023

BACKGROUND:
Advanced nodal disease is associated with poor prognosis. However, modern neoadjuvant systemic therapy (NST) regimens have resulted in higher pathologic complete response (pCR) rates, which are associated with improved survival. We sought to assess contemporary outcomes in patients with advanced nodal involvement and response to NST.

STUDY DESIGN:
We conducted a single-institution, retrospective study of 521 patients with cN2–3 primary nonmetastatic breast cancer treated with NST followed by surgery and radiation from 2012 to 2018. Descriptive statistics, multivariate Cox regression, and Kaplan–Meier analyses were performed.

RESULTS:
The mean age was 50.5 years, and median follow-up was 61 (4.7 to 197) months. The majority of patients had hormone receptor–positive (HR+)/HER2-negative tumors (HER2−; n = 242, 47.8%). Most were cT2 (n = 243; 46.6%) or cT3 (n = 139; 26.7%) and 73.3% (n = 382) had cN3 disease. Rate of axillary pCR was 34.2%, and breast and axillary pCR was 19.4% (n = 101). Event-free survival (EFS) at 5 years was 75.1% (95% CI, 0.71 to 0.79). Rate of locoregional recurrence was 6.7%; distant metastatic rate was 29.4%. Axillary pCR with or without breast pCR was significantly associated with longer EFS (p = 0.001). Achieving breast/axillary pCR was an independent predictor of improved EFS (hazard ratio 0.22, p < 0.0001). Having triple-negative disease was associated with worse EFS (hazard ratio 1.74, p = 0.008).

CONCLUSIONS:
In a high-risk cohort of patients with cN2–3 disease, trimodality therapy was effective in achieving durable EFS. Approximately one-third of patients achieved axillary pCR, which was associated with improved survival. Further studies are needed to accurately determine axillary response in cN2–3 breast cancer after NST in order to develop de-escalation strategies to reduce morbidity associated with axillary surgery.
Genetic diversity of clinical isolates of Mycobacterium tuberculosis complex circulating in Western Kenya
Authors: Chelimo Charles Komen , Angienda Paul Oyieng , Olwal Charles Ochieng , Nyamogoba Henry 
Published: October 2023

Tuberculosis (TB) remains a burden in many countries, including Kenya, especially, Western Kenya. Mycobacterium tuberculosis complex (MTBC) is the etiological agent of tuberculosis. TB burden is majorly linked to development of drug resistant strains. For treatment of TB, there is need for close surveillance of MTBC circulating in a given region. Hence, this study aimed to determine the proportion of MTBC species, strains and genetic diversity in circulation in an HIV prevalent region, western Kenya. Clinical isolates archived between 2013 and 2014 at Moi Teaching and Referral Hospital, Eldoret, Kenya with confirmed tuberculosis following Lowenstein-Jensen medium cultures were used. A 12-loci MIRU-VNTR genotyping was performed to determine the circulating species and strains of MTBC using www.MIRU-VNTRplus web platform. Allelic diversity was calculated using Hunters-Gaston diversity index (HGDI). The species identified in this population were M. tuberculosis, M. bovis and M. africanum, M. pinnipedii, M. microti, M. caprae and M. canetti. The strains were Beijing, Latin American Mediterranean (LAM), Uganda 1 and 2, East African Indian (EAI), Ilama, West African 1 and 2, Haelem, URAL, Ghana, Seal, Cameroon, Vole etc. Notably, some isolates had unknown (new/unassigned) species. The strains were grouped into nine clusters with clustering rate of 31.18%. The study revealed that there are multiple species and strains of Mycobacterium circulating in Western Kenya. These strains were moderately diverse as seen in the high allelic diversity index of 0.53. The present findings suggest that there is need for more awareness among healthcare and other stakeholders on the existence of foreign MTBC species and strains in Kenya. Furthermore, 12-loci MIRU-VNTR may not be suitable for surveillance of MTBC strains in circulation. High resolution techniques such as Whole Genome Sequencing need to be adopted to resolve the genetic diversityand establish evolutionary trends for future and archived samples. The knowledge will be crucial in curbing TB, giving insights into new drug development, TB prevention, control and treatment strategies.
The impact of light and thioredoxins on the plant thiol-disulfide proteome
Authors: Hou Liang-Yu , Sommer Frederik , Poeker Louis , Dziubek Dejan , Schroda Michael , Geigenberger Peter 
Published: October 2023

AbstractThiol-based redox regulation is a crucial post-translational mechanism to acclimate plants to changing light availability. Here, we conduct a biotin-switch-based redox proteomics study to systematically investigate dynamics of the thiol-redox network in response to temporal changes in light availability and across genotypes lacking parts of the thioredoxin (Trx) or NADPH-Trx-reductase C (NTRC) systems in the chloroplast. Time-resolved dynamics revealed light leading to marked decreases in the oxidation states of many chloroplast proteins with photosynthetic functions during the first 10 min, followed by their partial re-oxidation after 2-6 hours into the photoperiod. This involvedf,mandx-type Trx proteins showing similar light-induced reduction-oxidation dynamics, while NTRC, 2-Cys-Prx and Trxy2 showed an opposing pattern, being more oxidized in the light than the dark. In Arabidopsistrxf1f2,trxm1m2orntrcmutants, in the light most proteins showed increased oxidation states than wild type, suggesting their light-dependent dynamics being related to the NTRC/Trx networks. While NTRC deficiency had a strong influence in all light conditions, deficiencies inf- orm-type Trxs showed differential impacts on the thiol-redox proteome depending on the light environment, being higher in constant or fluctuating light, respectively. Results indicate plant redox proteomes to be subject to dynamic changes in reductive and oxidative pathways to cooperatively fine-tune photosynthetic and metabolic processes in the light. This involvesf-type Trxs and NTRC to play a role in constant medium light, while bothm-type Trxs and NTRC being important to balance changes in protein redox-pattern during dynamic alterations in fluctuating light intensities.One sentence summaryThe plant protein redoxome shows light-dependent reduction and reoxidation dynamics linked to Trxsf1/f2,m1/m2 and NTRC, being of different importance depending on the extent of light variability.
Dissolved gases from pressure changes in the lungs elicit an immune response in human peripheral blood
Authors: Harrell Abigail G. , Thom Stephen R. , Shields C. Wyatt 
Published: October 2023

AbstractConventional dogma suggests that decompression sickness (DCS) is caused by nitrogen bubble nucleation in the blood vessels and/or tissues; however, the abundance of bubbles does not correlate with DCS severity. Since immune cells respond to chemical and environmental cues, we hypothesized that the elevated partial pressures of dissolved gases drive aberrant immune cell phenotypes in the alveolar vasculature. To test this hypothesis, we measured immune responses within human lung-on–a-chip devices established with primary alveolar cells and microvascular cells. Devices were pressurized to 1.0 or 3.5 atm and surrounded by normal alveolar air or oxygen-reduced air. Phenotyping of neutrophils, monocytes, and dendritic cells as well as multiplexed ELISA revealed that immune responses occur within 1 hour and that normal alveolar air (i.e., hyperbaric oxygen and nitrogen) confer greater immune activation. This work strongly suggests innate immune cell reactions initiated at elevated partial pressures contribute to the etiology of DCS.Translational Impact StatementOur work reveals that the elevated partial pressures of dissolved gases within the vasculature drives immune cell activation. These findings have broad implications in identifying novel biomarkers for high-risk individuals (e.g., divers, pilots) through screening differential immune markers across patients. Further, this work offers a lens through which novel strategies to mitigate DCS in clinical scenarios may be employed by the delivery of prophylactic drugs that temper immune reactions.
Co-existence ofblaKPC-2andblaVIM-2in highly carbapenem-resistantPseudomonas aeruginosaisolated in the ICU of a public hospital
Authors: Zheng Lin , Wang Zixian , Guo Jingyi , Guan Jiayao , Li Quanliang , Lu Gejin , Jing Jie , Sun Shiwen , Sun Yang , Ji Xue , Jiang Bowen , Chen Ping , Wang Yongjie , Yang Yanling , Zhu Lingwei , Guo Xuejun 
Published: October 2023

AbstractIn this study, highly carbapenem-resistantPseudomonas aeruginosa(h-CRPA) 18102011 [the minimum inhibitory concentration (MIC) value of carbapenem antimicrobial imipenem (IP) for h-CRPA is 4,096 μg/mL] was isolated from the bile of an intensive care unit (ICU) burn patient in China, and genomic sequencing revealed a complete genome. The genome’s molecular characteristics were analyzed to assess the genetic environment ofblaKPC-2andblaVIM-2. Average nucleotide identity (ANI) comparisons were used for precise species-level identification, while serotyping, multi-locus sequence typing, and the identification of acquired resistance genes, and virulence genes were also carried out. The h-CRPA 18102011 strain carryingblaKPC-2andblaVIM-2was identified as strain ST2374 and the O4 serotype. Virulence genes (plcH,exoST) and resistance genes (aph(3’)-IIb,aac(6’)-Ib-cr,ant(2’’)-Ia,blaOXA-396,blaPAO,blaKPC-2,blaVIM-2,blaPER-1,sul1,catB7,qnrVC6,fosA) were both identified in the genome. In addition, the IncpRBL16type mega-plasmid pP2011-1 carryingblaVIM-2and the IncP6 type plasmid pP2011-2 carryingblaKPC-2were identified in the strain. The genetic environment ofblaVIM-2andblaKPC-2was specifically evaluated to assess their origins.blaVIM-2was located in the region of In2075 (a novel type 1 integron) that was inserted into plasmid pP2011-1, this plasmid contained 3 novel recombination sites, as well as the typical recombination site 2 (umuC) observed for IncpRBL16type plasmids. However, the core module Tn3-ISKpn27-blaKPC-ΔISKpn6was identified as theblaKPC-2platform in plasmid pP2011-2. Conjugation experiments revealed that the plasmids pP2011-1 and pP2011-2 of the h-CRPA 18102011 strain could be transferred intoEscherichia coliwith a conjugation transfer efficiency of 10-6. TheE. colitransconjugant carriedblaKPC-2andblaVIM-2from the donor and the MIC value of IP to theE. colitransconjugant was 4,096 μg/mL, which was the same as observed for the donor. Overall, this study revealed the molecular characteristics of a VIM-2 and KPC-2-co-producing strain that was typed as O4 and ST2374. The continuous monitoring of bacteria, such as the strain investigated here, that co-harbor different types of carbapenemase genes is critical for preventing the spread of these genes.
Bacterial vitamin B6 required for post-embryonic development inC. elegans
Authors: Feng Min , Gao Baizhen , Ruiz Daniela , Garcia L. Rene , Sun Qing 
Published: October 2023

AbstractNutritional intake influences animal growth, reproductive capacity, and survival of animals. Under nutrition deficiency, animal developmental arrest occurs as an adaptive strategy to survive. However, the nutritional basis and the underlying nutrient sensing mechanism essential for initiating animal regrowth after developmental arrest remain to be explored. InCaenorhabditis elegans, larvae undergo early developmental arrest are stress resistant, and they require certain nutrients to initiate postembryonic development. Here, we investigated the developmental arrest inC. elegansfeeding onLactobacillus plantarum, and the rescue of the diapause state with trace supplementation ofEscherichia coli. We performed a genome-wide screen using 3983 individual gene deletionE. colimutants and identifiedE. coligenes that are indispensable forC. eleganslarval growth on original not nutritionally sufficient bacteriaL. plantarum. Among these crucial genes, we confirmedE. coli pdxH, and the downstream metabolite pyridoxal 5-P (PLP, Vitamin B6) as essential nutritional factors initiatingC. eleganspostembryonic development. Transcriptome results suggest that bacterialpdxHaffects host development by coordinating host metabolic processes and PLP binding. Additionally, bacterial PLP may act as a cofactor for host tyrosine aminotransferase, thereby promoting the translocation of daf-16 to nucleus. Altogether, these results highlight the role of microbial metabolite PLP as a crucial micronutrient to recover postembryonic development inC. elegans.
ALCAM-mediated synapses between DC1 and CD8 T cells are inhibited in advanced lung tumors
Authors: Morosi Luciano G. , Piperno Giulia M. , Joshi Sonal , Amadio Roberto , Vodret Simone , López-Rodríguez Lucía , Benvenuti Federica 
Published: October 2023

AbstractConventional type 1 dendritic cells (DC1) control anti-tumoral CD8 T responses, in lymph nodes and tumor tissues. T-cell activation depends on the establishment of a tight physical interaction with antigen-presenting cell, the immunological synapse (IS). The molecular determinants of DC1-CD8 IS in tumor tissues and how they are regulated during cancer progression remain poorly investigated. Using a reporter for DC1 in a genetic model of non-small cell lung cancer (KP-XCR1venus) we show that IS in lung tissues are abundant and productive at early stages of tumor development but progressively diminish in advanced tumors. Transcriptional profiling and flow cytometry of lung resident DC1 identified a module of adhesion molecules downregulated in advanced tumors. We focused on ALCAM and LFA-1, ligands for CD6 and ICAM-1 on T cells, to investigate their role and functional impact. By immobilizing single receptor agonists on artificial cell surfaces, we demonstrate that ALCAM and LFA-1 are sufficient to trigger cytoskeletal remodeling in early tumor DC1, whereas late tumors DC1 are not responsive. Blocking ALCAM-CD6 interactions in functional assays impairs the acquisition of effector functions in CD8 T cells. Together these data highlight that adhesion molecules required to establish IS in early, immune-reactive, tumors are targeted during tumor progression blunting cross-talk within the IS.
Shoot-to-root mobile CEPD proteins regulate TGA transcription factors to allow nitrate root-to-shoot transport inArabidopsis thaliana
Authors: Pelizaeus Anja Maren , Thurow Corinna , Oskam Lisa , Hoßbach Ben Moritz , Budimir Jelena , Pierik Ronald , Gatz Christiane 
Published: October 2023

AbstractInArabidopsis thaliana, nitrogen (N) starvation leads to increased synthesis of CEPD (C-TERMINALLY ENCODED PEPTIDE DOWNSTREAM) proteins in the shoot. CEPDs travel to the roots, where they activate expression of genes required for high affinity nitrate transport. CEPDs belong to a plant-specific class of glutaredoxin-like proteins that interact with TGACG-binding transcription factors (TGAs). Here we identified the redundant clade-I TGAs TGA1 and TGA4 as the link between CEPDs and target promoters. In the absence of CEPDs, TGA1/4 have a strong negative effect on N starvation-induced gene expression leading to reduced translocation of N from the root to the shoot and to reduced shoot fresh weight. Basal levels of CEPDs were sufficient to completely release TGA1/4-mediated repression of nitrate acquisition. The antagonism between CEPDs and TGA1/4 was also detected in shoots, where CEPDs dampened the activating function of TGA1/4 on hyponasty and defense. CEPDs encode the conserved putative active site motif CxxC/S that was suggested to mediate redox regulation of target proteins. Complementation of thetga1 tga4mutant with a TGA1 variant containing amino acid substitutions of all four potentially redox-active cysteines showed that CEPDs do not regulate TGA1/4 by modulating their redox state.