bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure S4 from Immune-Related Colitis Is Associated with Fecal Microbial Dysbiosis and Can Be Mitigated by Fecal Microbiota Transplantation
Authors: Elkrief Arielle , Waters Nicholas R. , Smith Natalie , Dai Angel , Slingerland John , Aleynick Nathan , Febles Binita , Gogia Pooja , Socci Nicholas D. , Lumish Melissa , Giardina Paul A. , Chaft Jamie E. , Eng Juliana , Motzer Robert J. , Mendelsohn Robin B. , Markey Kate A. , Zhuang Mingqiang , Li Yanyun , Yang Zhifan , Hollmann Travis J. , Rudin Charles M. , van den Brink Marcel R.M. , Shia Jinru , DeWolf Susan , Schoenfeld Adam J. , Hellmann Matthew D. , Babady N. Esther , Faleck David M. , Peled Jonathan U.
Published: March 2024

Figure S4
Figure S1 from Immune-Related Colitis Is Associated with Fecal Microbial Dysbiosis and Can Be Mitigated by Fecal Microbiota Transplantation
Authors: Elkrief Arielle , Waters Nicholas R. , Smith Natalie , Dai Angel , Slingerland John , Aleynick Nathan , Febles Binita , Gogia Pooja , Socci Nicholas D. , Lumish Melissa , Giardina Paul A. , Chaft Jamie E. , Eng Juliana , Motzer Robert J. , Mendelsohn Robin B. , Markey Kate A. , Zhuang Mingqiang , Li Yanyun , Yang Zhifan , Hollmann Travis J. , Rudin Charles M. , van den Brink Marcel R.M. , Shia Jinru , DeWolf Susan , Schoenfeld Adam J. , Hellmann Matthew D. , Babady N. Esther , Faleck David M. , Peled Jonathan U.
Published: March 2024

Figure S1
Data from LILRB3 Supports Immunosuppressive Activity of Myeloid Cells and Tumor Development
Authors: Huang Ryan , Liu Xiaoye , Kim Jaehyup , Deng Hui , Deng Mi , Gui Xun , Chen Heyu , Wu Guojin , Xiong Wei , Xie Jingjing , Lewis Cheryl , Homsi Jade , Yang Xing , Zhang Chengcheng , He Yubo , Lou Qi , Smith Caroline , John Samuel , Zhang Ningyan , An Zhiqiang , Zhang Cheng Cheng
Published: March 2024

Abstract
The existing T cell–centered immune checkpoint blockade therapies have been successful in treating some but not all patients with cancer. Immunosuppressive myeloid cells, including myeloid-derived suppressor cells (MDSC), that inhibit antitumor immunity and support multiple steps of tumor development are recognized as one of the major obstacles in cancer treatment. Leukocyte Ig-like receptor subfamily B3 (LILRB3), an immune inhibitory receptor containing tyrosine-based inhibitory motifs (ITIM), is expressed solely on myeloid cells. However, it is unknown whether LILRB3 is a critical checkpoint receptor in regulating the activity of immunosuppressive myeloid cells, and whether LILRB3 signaling can be blocked to activate the immune system to treat solid tumors. Here, we report that galectin-4 and galectin-7 induce activation of LILRB3 and that LILRB3 is functionally expressed on immunosuppressive myeloid cells. In some samples from patients with solid cancers, blockade of LILRB3 signaling by an antagonistic antibody inhibited the activity of immunosuppressive myeloid cells. Anti-LILRB3 also impeded tumor development in myeloid-specific LILRB3 transgenic mice through a T cell–dependent manner. LILRB3 blockade may prove to be a novel approach for immunotherapy of solid cancers.
Data from Immune-Related Colitis Is Associated with Fecal Microbial Dysbiosis and Can Be Mitigated by Fecal Microbiota Transplantation
Authors: Elkrief Arielle , Waters Nicholas R. , Smith Natalie , Dai Angel , Slingerland John , Aleynick Nathan , Febles Binita , Gogia Pooja , Socci Nicholas D. , Lumish Melissa , Giardina Paul A. , Chaft Jamie E. , Eng Juliana , Motzer Robert J. , Mendelsohn Robin B. , Markey Kate A. , Zhuang Mingqiang , Li Yanyun , Yang Zhifan , Hollmann Travis J. , Rudin Charles M. , van den Brink Marcel R.M. , Shia Jinru , DeWolf Susan , Schoenfeld Adam J. , Hellmann Matthew D. , Babady N. Esther , Faleck David M. , Peled Jonathan U.
Published: March 2024

Abstract
Colitis induced by treatment with immune-checkpoint inhibitors (ICI), termed irColitis, is a substantial cause of morbidity complicating cancer treatment. We hypothesized that abnormal fecal microbiome features would be present at the time of irColitis onset and that restoring the microbiome with fecal transplant from a healthy donor would mitigate disease severity. Herein, we present fecal microbiota profiles from 18 patients with irColitis from a single center, 5 of whom were treated with healthy-donor fecal microbial transplantation (FMT). Although fecal samples collected at onset of irColitis had comparable α-diversity to that of comparator groups with gastrointestinal symptoms, irColitis was characterized by fecal microbial dysbiosis. Abundances of Proteobacteria were associated with irColitis in multivariable analyses. Five patients with irColitis refractory to steroids and biologic anti-inflammatory agents received healthy-donor FMT, with initial clinical improvement in irColitis symptoms observed in four of five patients. Two subsequently exhibited recurrence of irColitis symptoms following courses of antibiotics. Both received a second “salvage” FMT that was, again, followed by clinical improvement of irColitis. In summary, we observed distinct microbial community changes that were present at the time of irColitis onset. FMT was followed by clinical improvements in several cases of steroid- and biologic-agent-refractory irColitis. Strategies to restore or prevent microbiome dysbiosis in the context of immunotherapy toxicities should be further explored in prospective clinical trials.
Supplemental Figure 2 from Identification and Characterization of a Small Molecule Bcl-2 Functional Converter
Authors: Kopparapu Prasad R. , Pearce Martin C. , Löhr Christiane V. , Duong Cathy , Jang Hyo Sang , Tyavanagimatt Shanthakumar , O'Donnell Edmond F. , Nakshatri Harikrishna , Kolluri Siva K.
Published: March 2024

Bioluminescent imaging of data in Figure 7 for individual mouse treated with vehicle or BFC1108 is shown.
Clinical and Economic Insights into Parkinson’s Disease Hospitalization: A Comprehensive Study of 19,719 Inpatient Cases in Hubei Province, China
Authors: Liu Wen , Nie Pan , Zhang Jibo , Zhou Da , Zhang Jie , Chen Jincao
Published: March 2024

Objective: Parkinson’s disease (PD) is a profoundly incapacitating neurodegenerative disorder, which presents a substantial challenge to the economic sustainability of the global healthcare system. The present study seeks to clarify the factors that contribute to the costs associated with PD hospitalization and analyze the economic burden it imposes. Methods: We examined data of 19,719 patients with a primary diagnosis of PD who were admitted to hospitals in Hubei Province, China, during the study period. Healthcare data were obtained from the database of electronic medical records. The study presents a comprehensive analysis of the demographic characteristics and investigates the factors that affect their healthcare expenditure. Results: The cohort consisted of 10,442 (53.0%) males and 9,277 (47.0%) females. The age-group of 66–70 years experienced the highest incidence of hospitalization among PD patients, with a mortality rate of 0.76‰. The average length of stay for patients was 9.9 ± 8.6 days and the average cost per patient was USD 1,759.9 ± 4,787.7. Surgical interventions were conducted on a mere 2.0% of the total inpatient population. The primary cost component for these interventions was material expenses, accounting for 70.1% of the total. Non-surgical patients primarily incurred expenses related to diagnosis and medication. Notably, surgical patients faced a substantial out-of-pocket rate, reaching up to 90.6%. Surgery was identified as the most influential factor that negatively affected both length of stay and hospitalization costs. Inpatients exhibited significant associations with prolonged length of stay and increased medical expenditure as age increased. Male patients had significantly longer hospital stays and higher medical costs than did females. Additionally, patient’s occupation and type of medical insurance exerted significant effects on both length of stay and medical expense. Conclusion: Age significantly affects PD hospitalization costs. Given the prevailing demographic shift toward an aging population, the government’s medical insurance burden related to PD will continue to escalate. Meanwhile, high treatment expenses and out-of-pocket rates impose substantial financial burdens on patients, limiting surgical intervention access to a small fraction of patients. Addressing these issues is of utmost importance in order to ensure comprehensive disease management for the majority of individuals affected by PD.
C-Type Natriuretic Peptide Analogs: Current and Future Therapeutic Applications
Authors: Galetaki Despoina M. , Dauber Andrew
Published: March 2024

Background: Short stature is one of the most common reasons for referral to a pediatric endocrinologist that can be due to multitude of conditions, including an ever-growing list of genetic etiologies. Despite the numerous different causes, options for medical therapy remain quite limited, with the primary medication available being recombinant human growth hormone. A second option is recombinant insulin-like growth factor 1 (rIGF-1) in select patients with severe primary IGF-1 deficiency. Alternative strategies to increase height have been attempted such as delaying the onset of puberty with a gonadotropin-releasing hormone agonist or delaying epiphyseal fusion with an aromatase inhibitor. However, these options focus on increasing the duration of growth as opposed to directly stimulating growth at the growth plate. Summary: Novel approaches to growth promotion have recently been developed, including analogs of C-type natriuretic peptide (CNP). The purpose of this study is to review the function of CNP and its potential use in different conditions. Key Messages: Alterations in the CNP/FGFR3 pathway can lead to multiple defined genetic causes of short stature. The CNP pathway has become the focus for treatment of children with short stature that suffer from such genetic conditions, with promising outcomes.
Primary Nodal Epstein-Barr Virus-Positive T-Cell/NK-Cell Lymphoma: Real-World Experience
Authors: Choi Dae-Ho , Yoon Sang Eun , Cho Junhun , Kim Seok Jin , Kim Won Seog
Published: March 2024

Introduction: Primary nodal Epstein-Barr virus-positive T-cell/NK-cell lymphoma (PTCL-EBV) is a disease entity newly recognized in the World Health Organization’s classification of hematolymphoid tumors, 5th edition (WHO-HAEMS5) and the International Consensus Classification of Mature Lymphoid Neoplasms (ICC). Previously, it was classified as a subtype within peripheral T-cell lymphoma, not otherwise specified, and was known to have a poor prognosis. However, the clinical features and treatment outcomes are not well known. Methods: This retrospective observational study was conducted on patients diagnosed with PTCL-EBV at Samsung Medical Center through a pathology review from 2000 to 2020. We analyzed the clinical data from 14 patients, immunohistochemistry, and survival outcomes including overall survival (OS) and progression-free survival (PFS) for each treatment regimen. PFS was defined as the time from the start of chemotherapy to the confirmation of disease progression on imaging, and hematopoietic stem-cell transplantation (HSCT) was considered a consolidation treatment. OS was defined as the time from diagnosis to the time of death. Results: 25% (1 out of 4) were beta-F1 positive, and 67% (4 out of 6) were T-cell receptor gamma (TCRγ) positive. T-cell intracellular antigen (TIA-1) and granzyme B exhibited positive results in all cases (3 out of 3), whereas the NK-cell marker CD56 was positive in only 11% of patients (1 out of 9). CD3 was observed in all of the patients (11 out of 11). The CD4 was 43% positive (3 out of 7). The CD8 was investigated in 8 patients, with 37.5% positive (3 out of 8). Hepatosplenomegaly was observed in 55% of patients (6 out of 11), and 70% (7 out of 10) of patients displayed B symptoms at the time of diagnosis. Patients who received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) or CVP (cyclophosphamide, vincristine, prednisolone) treatment had a median PFS of 2.2 months (95% CI: 1.9–2.5 months), and patients who received other treatments had a median PFS of 5.1 months (NA). The objective response rate (ORR) for ICE/dexa (ifosfamide, carboplatin, etoposide, dexamethasone) as the first- or second-line treatment was 100% (3 out of 3). But ORR of CHOP or CVP as the first-line treatment was 33.3% (3 out of 9). The median OS for the group that received HSCT (3 out of 11) after achieving a response was 34.6 months (95% CI: 0–74.6 months), and the median OS for the group that did not receive HSCT (8 out of 11) was 5.0 months (95% CI: 2.1–7.9 months) (p = 0.04). Conclusions: In conclusion, in the context of PTCL-EBV, despite a limited sample size, the ICE/Dexa regimen shows potential benefits in terms of ORR and PFS. Furthermore, the application of HSCT following the attainment of a complete response may prove advantageous.
Torsemide Versus Furosemide After Discharge in Patients Hospitalized With Heart Failure Across the Spectrum of Ejection Fraction: Findings From TRANSFORM-HF
Authors: Kapelios Chris J. , Greene Stephen J. , Mentz Robert J. , Ikeaba Uchechukwu , Wojdyla Daniel , Anstrom Kevin J. , Eisenstein Eric L. , Pitt Bertram , Velazquez Eric J. , Fang James C. ,   TRANSFORM-HF Investigators
Published: March 2024

BACKGROUND:

The TRANSFORM-HF trial (Torsemide Comparison With Furosemide for Management of Heart Failure) found no significant difference in all-cause mortality or hospitalization among patients randomized to a strategy of torsemide versus furosemide following a heart failure (HF) hospitalization. However, outcomes and responses to some therapies differ by left ventricular ejection fraction (LVEF). Thus, we sought to explore the effect of torsemide versus furosemide by baseline LVEF and to assess outcomes across LVEF groups.

METHODS:

We compared baseline patient characteristics and randomized treatment effects for various end points in TRANSFORM-HF stratified by LVEF: HF with reduced LVEF, ≤40% versus HF with mildly reduced LVEF, 41% to 49% versus HF with preserved LVEF, ≥50%. We also evaluated associations between LVEF and clinical outcomes. Study end points were all-cause mortality or hospitalization at 30 days and 12 months, total hospitalizations at 12 months, and change from baseline in Kansas City Cardiomyopathy Questionnaire clinical summary score.

RESULTS:

Overall, 2635 patients (median 64 years, 36% female, 34% Black) had LVEF data. Compared with HF with reduced LVEF, patients with HF with mildly reduced LVEF and HF with preserved LVEF had a higher prevalence of comorbidities. After adjusting for covariates, there was no significant difference in risk of clinical outcomes across the LVEF groups (adjusted hazard ratio for 12-month all-cause mortality, 0.91 [95% CI, 0.59–1.39] for HF with mildly reduced LVEF versus HF with reduced LVEF and 0.91 [95% CI, 0.70–1.17] for HF with preserved LVEF versus HF with reduced LVEF;
P
=0.73). In addition, there was no significant difference between torsemide and furosemide (1) for mortality and hospitalization outcomes, irrespective of LVEF group and (2) in changes in Kansas City Cardiomyopathy Questionnaire clinical summary score in any LVEF subgroup.

CONCLUSIONS:

Despite baseline demographic and clinical differences between LVEF cohorts in TRANSFORM-HF, there were no significant differences in the clinical end points with torsemide versus furosemide across the LVEF spectrum. There was a substantial risk for all-cause mortality and subsequent hospitalization independent of baseline LVEF.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03296813.
Optimising the sensitivity of optically-pumped magnetometer magnetoencephalography to gamma band electrophysiological activity
Authors: Hill Ryan M. , Schofield Holly , Boto Elena , Rier Lukas , Osborne James , Doyle Cody , Worcester Frank , Hayward Tyler , Holmes Niall , Bowtell Richard , Shah Vishal , Brookes Matthew J.
Published: March 2024

The measurement of electrophysiology is of critical importance to our understanding of brain function. However, current non-invasive measurements—electroencephalography (EEG) and magnetoencephalography (MEG)—have limited sensitivity, particularly compared to invasive recordings. Optically-Pumped Magnetometers (OPMs) are a new type of magnetic field sensor which ostensibly promise MEG systems with higher sensitivity; however, the noise floor of current OPMs remains high compared to cryogenic instrumentation and this limits the achievable signal-to-noise ratio of OPM-MEG recordings. Here, we investigate how sensor array design affects sensitivity, and whether judicious sensor placement could compensate for the higher noise floor. Through theoretical analyses, simulations, and experiments, we use a beamformer framework to show that increasing the total signal measured by an OPM array—either by increasing the number of sensors and channels, or by optimising the placement of those sensors—affords a linearly proportional increase in signal-to-noise ratio (SNR) following beamformer reconstruction. Our experimental measurements confirm this finding, showing that by changing sensor locations in a 90-channel array, we could increase the SNR of visual gamma oscillations from 4.8 to 10.5. Using a 180-channel optimised OPM-array, we capture broadband gamma oscillations induced by a naturalistic visual paradigm, with an SNR of 3; a value that compares favourably to similar measures made using conventional MEG. Our findings show how an OPM-MEG array can be optimised to measure brain electrophysiology with the highest possible sensitivity. This is important for the design of future OPM-based instrumentation.
A new species of the genus Trichopagurus de Saint Laurent, 1968 (Crustacea: Decapoda: Anomura: Paguridae) from a semi-submerged marine cave in Okinawa Island, southwestern Japan
Authors: NAKAJIMA HIROKI , FUJITA YOSHIHISA , OSAWA MASAYUKI
Published: March 2024

A new hermit crab species of Paguridae, Trichopagurus spinibrachium n. sp., is described on the basis of a single male specimen collected from the anchialine environment of a semi-submerged marine cave in Okinawa Island, Ryukyu Islands, southwestern Japan. It is morphologically similar to T. macrochela Komai & Osawa, 2005 and T. tenuidactylus Komai, 2013, but differs in the shape and armature of the ocular, antennular and antennal peduncles, chelipeds, and ambulatory legs. The new species may be distinguished from all known congeners by the stronger armature of the carpi and meri of both chelipeds. Trichopagurus spinibrachium n. sp. is the third species of the genus recorded from submarine caves, although it may also occur on nearby coral reefs as does T. macrochela and T. trichophthalmus (Forest, 1954).
Taxonomic review of the monotypic genus Dinahia Bechyně, 1946 (Coleoptera: Chrysomelidae: Chrysomelinae)
Authors: SAMPAIO ALINE , FONSECA CLAUDIO RUY VASCONCELOS DA
Published: March 2024

The monotypic genus Dinahia Bechyně, 1946, endemic to the Atlantic Forest (Rio Grande do Sul, Santa Catarina, and São Paulo), is reviewed. Dinahia privigna Bechyně, 1946 is redescribed, and, for the first time, the aedeagus and spermatheca of this species are described and illustrated herein. Additionally, a diagnosis for the genus, a nomenclatural history, photographs of both non–type specimens and the syntype, a geographic distribution map, and a discussion of Dinahia and similar genera according to the bibliography (Calligrapha Chevrolat, 1836; Cosmogramma Erichson, 1847; Desmogramma Erichson, 1847; Grammomades Achard, 1923; and Zygogramma Chevrolat, 1836) are provided. This discussion incorporates a comparative table encompassing characters extracted from the antennae, maxillary palps, prosternal, mesoventral, and metaventral processes, V tarsomeres, and claws. Additionally, it includes an illustrated replacement couplet for step 22 in Sampaio & Fonseca's (2023) identification key, both to elucidate Dinahia's differentiations and similarities from these five genera.
Reliability analysis of wind turbines considering seasonal weather effects
Authors: Zheng Rui , Song Yanying , Fang Haojun
Published: March 2024

The failure rate of wind turbines shows obvious fluctuation due to seasonal environmental factors. However, few efforts have been devoted to modeling the seasonal failure rate. This paper develops a novel model that consists of a baseline failure rate function, seasonal indices, and a residual term to describe the monthly failure rate of wind turbines. A two-stage procedure is developed to estimate the 16 unknown parameters in the model. The first stage explores the relationship between the parameters in the baseline function and the monthly coefficients by maximum likelihood estimation and then integrates the properties into the genetic algorithm to estimate the main parameters. In the second stage, the variance of the residual term is estimated based on the analysis of the differences between the observed and predicted failure rates. The failure history of 48 months has been used to illustrate the proposed approach. The results show that the monthly failure rate function can well fit the real failure history of wind turbines, and it outperforms the traditional reliability model.
TonEBP/NFAT5 expression is associated with cisplatin resistance and migration in macrophage-induced A549 cells
Authors: Song Hee Ju , Kim Young Hwan , Choi Han Na , Kim Taehee , Kim Soo Jin , Kang Min Woong , Lee Sang Do
Published: March 2024

Background

Macrophages promote angiogenesis, metastasis, and drug resistance in several cancers. Similarly, TonEBP/NFAT5 induces metastasis in renal carcinoma and colon cancer cells. However, the role of this transcription factor and that of macrophages in lung cancer cells remains unclear. Therefore, this study investigated the effects of macrophages and TonEBP/NFAT5 expression on cisplatin resistance and migration in A549 lung adenocarcinoma cells.

Results

A549 cells were cultured alone or indirectly co-cultured with THP-1-derived macrophages using a transwell culture chamber. Cisplatin-induced cell death was markedly decreased and migration increased in co-cultured A549 cells. Macrophage-conditioned media (CM) showed a similar effect on drug resistance and migration. Cisplatin-induced apoptosis, DNA fragmentation, and cleaved apoptotic proteins PARP and caspase-3 were markedly reduced in macrophage CM-induced A549 cells. Here, ERK, p38, JNK, and NF-κB activities were increased by macrophage CM. Furthermore, the proteins involved in cisplatin resistance and cancer cell migration were identified using specific inhibitors of each protein. ERK and NF-κB inhibition considerably reduced cisplatin resistance. The increase in macrophage CM-induced migration was partially reduced by treatment with ERK, JNK, and NF-κB inhibitors. TonEBP/NFAT5 expression was increased by macrophages, resulting in increased cisplatin resistance, cell migration, and invasion. Moreover, RNAi-mediated knockdown of TonEBP/NFAT5 reduced cisplatin resistance, migration, and invasion in macrophage CM-induced A549 cells.

Conclusions

These findings demonstrate that paracrine factors secreted from macrophages can change A549 cells, resulting in the induction of drug resistance against cisplatin and migration. In addition, the TonEBP/NFAT5 ratio, increased by macrophages, is an important regulator of the malignant transformation of cells.
Genome-wide identification, expression profiling, and protein interaction analysis of the CCoAOMT gene family in the tea plant (Camellia sinensis)
Authors: Wang Yiqing , Wang Tao , Qi Siyu , Zhao Jiamin , Kong Jiumei , Xue Zhihui , Sun Weijiang , Zeng Wen
Published: March 2024

Background

The caffeoyl-CoA-O methyltransferase (CCoAOMT) family plays a crucial role in the oxidative methylation of phenolic substances and is involved in various plant processes, including growth, development, and stress response. However, there is a limited understanding of the interactions among CCoAOMT protein members in tea plants.

Results

In this study, we identified 10 members of the CsCCoAOMT family in the genome of Camellia sinensis (cultivar ‘HuangDan’), characterized by conserved gene structures and motifs. These CsCCoAOMT members were located on six different chromosomes (1, 2, 3, 4, 6, and 14). Based on phylogenetic analysis, CsCCoAOMT can be divided into two groups: I and II. Notably, the CsCCoAOMT members of group Ia are likely to be candidate genes involved in lignin biosynthesis. Moreover, through the yeast two-hybrid (Y2H) assay, we established protein interaction networks for the CsCCoAOMT family, revealing 9 pairs of members with interaction relationships.

Conclusions

We identified the CCoAOMT gene family in Camellia sinensis and conducted a comprehensive analysis of their classifications, phylogenetic and synteny relationships, gene structures, protein interactions, tissue-specific expression patterns, and responses to various stresses. Our findings shed light on the evolution and composition of CsCCoAOMT. Notably, the observed interaction among CCoAOMT proteins suggests the potential formation of the O-methyltransferase (OMT) complex during the methylation modification process, expanding our understanding of the functional roles of this gene family in diverse biological processes.
Prodromal Parkinson disease signs are predicted by a whole-blood inflammatory transcriptional signature in young Pink1−/− rats
Authors: Lechner Sarah A. , Barnett David G. S. , Gammie Stephen C. , Kelm-Nelson Cynthia A.
Published: March 2024

Background

Parkinson disease (PD) is the fastest growing neurodegenerative disease. The molecular pathology of PD in the prodromal phase is poorly understood; as such, there are no specific prognostic or diagnostic tests. A validated Pink1 genetic knockout rat was used to model early-onset and progressive PD. Male Pink1−/− rats exhibit progressive declines in ultrasonic vocalizations as well as hindlimb and forelimb motor deficits by mid-to-late adulthood. Previous RNA-sequencing work identified upregulation of genes involved in disease pathways and inflammation within the brainstem and vocal fold muscle. The purpose of this study was to identify gene pathways within the whole blood of young Pink1−/− rats (3 months of age) and to link gene expression to early acoustical changes. To accomplish this, limb motor testing (open field and cylinder tests) and ultrasonic vocalization data were collected, immediately followed by the collection of whole blood and RNA extraction. Illumina® Total RNA-Seq TruSeq platform was used to profile differential expression of genes. Statistically significant genes were identified and Weighted Gene Co-expression Network Analysis was used to construct co-expression networks and modules from the whole blood gene expression dataset as well as the open field, cylinder, and USV acoustical dataset. ENRICHR was used to identify the top up-regulated biological pathways.

Results

The data suggest that inflammation and interferon signaling upregulation in the whole blood is present during early PD. We also identified genes involved in the dysregulation of ribosomal protein and RNA processing gene expression as well as prion protein gene expression.

Conclusions

These data identified several potential blood biomarkers and pathways that may be linked to anxiety and vocalization acoustic parameters and are key candidates for future drug-repurposing work and comparison to human datasets.
Non-alcoholic fatty liver disease in Tanzania: prevalence, determinants, and diagnostic performance of triglycerides-glucose index and triglycerides-glucose index –body mass index compared to the hepatic ultrasound in overweight and obese individuals
Authors: Kilonzo Semvua B. , Kamala Eliud , Jaka Hyasinta , Ngoya Patrick
Published: March 2024

Background

Non-alcoholic fatty liver disease (NAFLD), which is closely associated with metabolic syndrome (MetS), is rarely reported in Tanzania, where MetS is prevalent. The purpose of this study was to determine the prevalence and associated factors of this condition in overweight and obese individuals and to correlate standard ultrasound diagnosis with triglyceride-glucose index (TyG) and TyG-body mass index (TyG-BMI).

Methods

A cross-sectional analysis was performed in 181 adult outpatients attending a general medical clinic. The presence of fatty liver was detected by ultrasound. Demographic, clinical, and laboratory data were collected and analyzed using STATA 15. To compare categorical variables, a chi-square test was employed, while a Student’s t-test was used to compare continuous variables. Additionally, a multivariate regression analysis was conducted to identify the determinants of NAFLD. A significance level was set at p < 0.05. The discriminatory power of TyG and TyG-BMI for diagnosing NAFLD was evaluated using Receiver Operating Characteristic (ROC) Curve analysis and the Area Under the ROC Curve (AUC) was reported.

Results

The overall prevalence of NAFLD was 30.4% (55/181). The prevalence’s of NAFLD in patients with class III obesity, class II obesity, class I obesity and overweight were 50.0% (12/24),, 38% (19/50), 23.7% (18/76), and 19.5% (6/31),respectively. NAFLD was strongly predicted by hyperuricemia (≥ 360 μmol/L) (p = 0.04) and TyG ≥ 8.99 (p = 0.003). The best cut-off values of TyG and TyG-BMI to predict NAFLD were 8.99 [AUC 0.735; sensitivity 70.9%, specificity 79.3%] and 312 [AUC 0.711; sensitivity 60% and specificity 75.4%] respectively.

Conclusions

The prevalence of NAFLD is high among people with overweight and obesity in Tanzania. We did not find sufficient evidence to recommend the use of TyG and TyG-BMI as surrogates for hepatic ultrasound in detecting NAFLD, and further evaluation is recommended.
Comparison of prognostic outcomes between endoscopic submucosal dissection and surgical treatment for early gastric cancer: a retrospective cohort study
Authors: Zhang Yifan , Shi Fangzhen , Fan Yuxiang , Liu Gang , Xia Chengkai , Wang Haodong
Published: March 2024

Background and aim

The optimal management strategy for early gastric cancer (EGC) a topic of contention. This study aims to compare the prognostic outcomes of endoscopic submucosal dissection (ESD) and surgical treatment in patients diagnosed with EGC.

Methods

In thisretrospective cohort study, we analyzed data from539 patients diagnosed with EGC between January 2012 and December 2020 from two centers. We compared Clinicopathological features, procedure-related complications, recurrence rate, overall survival, and disease specific survival between the 262 patients who underwent ESD and the 277 patients who underwent surgical treatment. ESD procedures were conducted using a dual knife by experienced endoscopists, while surgical treatments included laparoscopic or open gastrectomy. Regular ollow-up examinations were conducted post-treatment.

Results

The two groups exhibited comparable baseline characteristics. Multivariable Cox regression analysis identified vascular invasion as a risk factor for worse recurrence-free survival (RFS), and overall survival (OS) in patients with early gastric cancer. The ESD group experienced fewer overall postoperative complications compared to the surgical treatment group. Kaplan-Meier curves demonstrated no significant differences in recurrence rate or overall survival between the two groups.

Conclusions

Both ESD and surgical treatment emerged as safe and effective approaches for managing EGC. The choice of treatment should be tailored to individual patient factors. ESD can be considered an alternative treatment option for selected patients who are not suitable candidates for surgery. Further studies are warranted to determine the long-term outcomes of ESD and surgical treatment for EGC.
Development of a multidisciplinary medication management program in nursing homes: protocol for a randomized controlled trial
Authors: Lee Hye Jun , Jang Sunmee , Lee Ju-Yeun , Ah Young-Mi , Lee Mi-Kyung , Jang Suhyun , An Sena , Kim Jung-Ha
Published: March 2024

Background

Polypharmacy and the use of potentially inappropriate medications are common among nursing home residents and are associated with negative outcomes. Although deprescribing has been proposed as a way to curtail these problems, the best way to implement multidisciplinary comprehensive medication review and deprescribing and its real impact in specific high-risk populations, such as nursing home residents, is still unclear. This multicenter randomized controlled clinical trial aims to assess the effects of a multidisciplinary mediation management program on medication use and health problems.

Methods

A total of 1,672 residents aged ≥ 65 years from 22 nursing homes in South Korea who meet the targeted criteria, such as the use of ≥ 10 medications, are eligible to participate. The experimental group will receive a comprehensive medication review, deprescription, and multidisciplinary case conference with the help of platform. Outcomes will be measured at baseline, at the end of the intervention, as well as at 3, 6, 9, and 12 months after the end of the intervention. The primary endpoints will be the rate of adverse drug events, number of potentially inappropriate medications/potentially inappropriate medication users/two or more central nervous system drug/ central nervous system drug users, delirium, emergency department visits, hospitalization, and falls. The secondary endpoint will be the number of medications taken and polypharmacy users.

Discussion

Our trial design is unique in that it aims to introduce a structured operationalized clinical program focused on reducing polypharmacy and potentially inappropriate medications in a nursing home setting with large samples.

Trial registration

Ethical approval was granted by the public institutional review board of the Ministry of Health and Welfare (2022-1092-009). The study is also registered with the Clinical Research Information Service (Identifier: KCT0008157, Development and evaluation of a multidisciplinary medication management program in long-term care facility residents Status: Approved First Submitted Date: 2023/01/18 Registered Date: 2023/02/03 Last Updated Date: 2023/01/18 (nih.go.kr) https://cris.nih.go.kr/), which includes all items from the World Health Organization Trial Registration Dataset.
The RdRp genotyping of SARS-CoV-2 isolated from patients with different clinical spectrum of COVID-19
Authors: Majchrzak Michał , Madej Łukasz , Łysek-Gładysińska Małgorzata , Zarębska-Michaluk Dorota , Zegadło Katarzyna , Dziuba Anna , Nogal-Nowak Katarzyna , Kondziołka Wioleta , Sufin Iwona , Myszona-Tarnowska Mieczysława , Jaśkowski Mateusz , Kędzierski Mateusz , Maciukajć Jadwiga , Matykiewicz Jarosław , Głuszek Stanisław , Adamus-Białek Wioletta
Published: March 2024

Background

The evolution of SARS-CoV-2 has been observed from the very beginning of the fight against COVID-19, some mutations are indicators of potentially dangerous variants of the virus. However, there is no clear association between the genetic variants of SARS-CoV-2 and the severity of COVID-19. We aimed to analyze the genetic variability of RdRp in correlation with different courses of COVID-19.

Results

The prospective study included 77 samples of SARS-CoV-2 isolated from outpatients (1st degree of severity) and hospitalized patients (2nd, 3rd and 4th degree of severity). The retrospective analyses included 15,898,266 cases of SARS-CoV-2 genome sequences deposited in the GISAID repository. Single-nucleotide variants were identified based on the four sequenced amplified fragments of SARS-CoV-2. The analysis of the results was performed using appropriate statistical methods, with p < 0.05, considered statistically significant. Additionally, logistic regression analysis was performed to predict the strongest determinants of the observed relationships. The number of mutations was positively correlated with the severity of the COVID-19, and older male patients. We detected four mutations that significantly increased the risk of hospitalization of COVID-19 patients (14676C > T, 14697C > T, 15096 T > C, and 15279C > T), while the 15240C > T mutation was common among strains isolated from outpatients. The selected mutations were searched worldwide in the GISAID database, their presence was correlated with the severity of COVID-19.

Conclusion

Identified mutations have the potential to be used to assess the increased risk of hospitalization in COVID-19 positive patients. Experimental studies and extensive epidemiological data are needed to investigate the association between individual mutations and the severity of COVID-19.
Comparison of therapeutic effects between big-bubble deep anterior lamellar keratoplasty and penetrating keratoplasty for medically unresponsive Acanthamoeba keratitis
Authors: Qi Xiaolin , Mao Huilin , Liu Jinhui , Dong Yanling , Du Man , Liu Ting , Zhang Ting , Lu Xiuhai , Gao Hua
Published: March 2024

Purpose

To compare the outcomes of big-bubble deep anterior lamellar keratoplasty (BB-DALK) and penetrating keratoplasty (PKP) in the management of medically unresponsive Acanthamoeba keratitis (AK).

Methods

This retrospective study included 27 eyes of BB-DALK and 24 eyes of PKP from a tertiary ophthalmology care centre. Glucocorticoid eye drops were subsequently added to the treatment plan 2 months postoperatively based on the evaluation using confocal laser scanning microscopy. The clinical presentations, best-corrected visual acuity (BCVA), postoperative refractive outcomes, graft survival, and Acanthamoeba recurrence were analyzed.

Results

The AK patients included in the study were in stage 2 or stage 3, and the percentage of patients in stage 3 was higher in the PKP group (P = 0.003). Clinical presentations were mainly corneal ulcers and ring infiltrates, and endothelial plaques, hypopyon, uveitis and glaucoma were more common in the PKP group (P = 0.007). The BCVA and the graft survival rate showed no statistically significant differences between the two groups at 1 year after surgery. However, 3 years postoperatively, the BCVA of 0.71 ± 0.64 logMAR, the graft survival rate of 89.5%, and the endothelial cell density of 1899 ± 125 cells per square millimeter in the BB-DALK group were significantly better than those of the PKP group (P = 0.010, 0.046, and 0.032, respectively). 3 eyes (11.1%) in the BB-DALK group and 2 eyes (8.3%) in the PKP group experienced Acanthamoeba recurrence, but the rates showed no statistically significant difference between the two groups (P = 1.000). In the PKP group, immune rejection and elevated intraocular pressure were observed in 5 and 6 eyes, respectively.

Conclusion

Corneal transplantation is recommended for AK patients unresponsive to antiamoebic agents. The visual acuity and graft survival can be maintained after BB-DALK surgery. Acanthamoeba recurrence is not related to the surgical approach performed, whereas complete dissection of the infected corneal stroma and delayed prescribing of glucocorticoid eye drops were important to prevent recurrence.
Causal effects of gut microbiome on HIV infection: a two-sample mendelian randomization analysis
Authors: Li Kangjie , Zhang Cong , Deng Jielian , Zeng Haijiao , Zhang Yuan , Lai Guichuan , Zhong Xiaoni , Xie Biao
Published: March 2024

Background

The causal association between gut microbiome and HIV infection remains to be elucidated. We conducted a two-sample mendelian randomization analysis to estimate the causality between gut microbiome and HIV infection.

Methods

Publicly released genome-wide association studies summary data were collected to perform the mendelian analysis. The GWAS summary data of gut microbiome was retrieved from the MiBioGen consortium, which contains 18 340 samples from 24 cohorts. GWAS summary data of HIV infection was collected from the R5 release of FinnGen consortium, including 357 HIV infected cases and 218 435 controls. The SNPs were selected as instrumental variables according to our selection rules. And SNPs with a F-statistics less than ten were regarded as weak instrumental variables and excluded. Mendelian randomization analysis was conducted by five methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode. The Cochran’s Q test and MR-Egger intercept test were performed to identify heterogeneity and pleiotropy. Leave-one-out analysis were used to test the sensitivity of the results.

Results

Fifteen gut microbiota taxa showed causal effects on HIV infection according to the MR methods. Four taxa were observed to increase the risk of HIV infection, including Ruminococcaceae (OR: 2.468[1.043, 5.842], P: 0.039), RuminococcaceaeUCG005 (OR: 2.051[1.048, 4.011], P: 0.036), Subdoligranulum (OR: 3.957[1.762, 8.887], P < 0.001) and Victivallis (OR: 1.605[1.012, 2.547], P=0.044). Erysipelotrichaceae was protective factor of HIV infection (OR: 0.278[0.106, 0.731], P < 0.001) and Methanobrevibacter was also found to be associated with reduced risk of HIV infection (OR: 0.509[0.265, 0.980], P=0.043). Horizontal pleiotropy was found for Fusicatenibacter (P<0.05) according to the MR-Egger regression intercept analysis. No heterogeneity was detected.

Conclusion

Our results demonstrate significant causal effects of gut microbiome on HIV infection. These findings facilitate future studies to develop better strategies for HIV prophylaxis through gut microbiome regulation. Further explorations are also warranted to dissect the mechanism of how gut microbiome affects HIV susceptibility.
Comprehensive evaluation of serum hepatic proteins in predicting prognosis among cancer patients with cachexia: an observational cohort study
Authors: Huang Jia-Xin , Zhang Xi , Tang Meng , Zhang Qi , Deng Li , Song Chun-Hua , Li Wei , Shi Han-Ping , Cong Ming-Hua
Published: March 2024

Background

Hepatic proteins, including albumin, prealbumin, and transferrin have been confirmed to be prognostic predictors in various cancers. This study aimed to comprehensively assess the prognostic value of these three serum markers in patients with cancer cachexia.

Methods

This multicenter prospective cohort study included 1303 cancer cachexia patients, among whom 592 deaths occurred during a median follow-up of 20.23 months. The definition of cachexia was based on the 2011 international consensus. Concordance index (C-index) and receiver operating characteristic (ROC) curves were applied to compare the prognostic performance. The primary outcome was overall survival, which was calculated using the Kaplan–Meier method generated by log-rank test. A Cox proportional hazard regression model was used to identify independent predictors associated with survival. The secondary outcomes included 90-days mortality and quality of life (QoL).

Results

C-index and ROC curves showed that albumin had the most accurate predictive capacity for survival, followed by transferrin and prealbumin. Multivariate Cox analysis confirmed that low albumin (hazard ratio [HR] = 1.51, 95% confidence interval [95%CI] = 1.28–1.80, P < 0.001), prealbumin (HR = 1.42, 95%CI = 1.19–1.69, P < 0.001), and transferrin (HR = 1.50, 95%CI = 1.25–1.80, P < 0.001) were independent risk factors for long-term survival in cancer patients with cachexia. In subgroup analysis, the prognostic value of low albumin was significant in patients with upper gastrointestinal, hepatobiliary and pancreatic, and colorectal cancers; low prealbumin was significant in colorectal cancer; and low transferrin was significant in patients with upper gastrointestinal and colorectal cancer. All three hepatic proteins were valuable as prognostic predictors for patients with advanced (Stage III and IV) cancer with cachexia. The risks of 90-days mortality and impaired QoL were higher in cachexia patients with low albumin, prealbumin, and transferrin levels.

Conclusion

Low albumin, prealbumin, and transferrin levels were all independent prognostic factors affecting patients with cancer cachexia, especially in patients in the advanced stages. These results highlight the value of routinely checking serum hepatic proteins in clinical practice to predict the prognosis of patients with cancer cachexia.
Identification of PANoptosis-related signature reveals immune infiltration characteristics and immunotherapy responses for renal cell carcinoma
Authors: Xu Yan , Hua Jingqi , Que Hongliang , Zeng Tengyue , Li Quan , Deng Junpeng , Xie Jianjun
Published: March 2024

PANoptosis is a specific type of inflammatory programmed cell death (PCD) modality that can be involved in three key modes of cellular programmed cell death-pyroptosis, apoptosis and necroptosis. We analyzed PANoptosis activity in three common renal cell carcinoma subtypes (Clear cell renal cell carcinoma, Papillary renal cell carcinoma, and Chromophobe renal cell carcinoma) separately and constructed a new PANoptosis immunity index (PANII). In three renal cell carcinomas, we found that PANII was an effective predictor of immunotherapy efficacy in KIRC, KIRP and KICH, and the high PANII group was characterized by high immune infiltration and sensitivity to immunotherapy, while the low PANII group was prone to immune escape and immunotherapy resistance. We performed molecular docking prediction of each core protein comprising PANII and identified natural small molecule compounds with the highest affinity to target proteins. In addition, we found that down-regulation of PYCARD inhibited the proliferation and migration of renal clear cell carcinoma cells by in vitro functional assays, suggesting that PYCARD could be a novel target for renal clear cell carcinoma therapy. Our findings that the PANoptosis characterization-based index (PANII) helps to elucidate the tumor microenvironmental features of three common renal cell carcinoma subtypes and identify patient populations that will benefit from immunotherapy, providing a new tool for the clinical diagnosis and treatment of patients with intermediate- and advanced-stage renal cell carcinoma.