bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative sintilimab plus transarterial chemoembolization for hepatocellular carcinoma exceeding the Milan criteria: A phase II trial
Authors: Guo Chengxiang , Zhang Junlei , Huang Xin , Chen Yiwen , Sheng Jianpeng , Huang Xing , Sun Junhui , Xiao Wenbo , Sun Ke , Gao Shunliang , Que Risheng , Shen Yan , Zhang Min , Wu Jian , Bai Xueli , Liang Tingbo 
Published: February 2023

Background and aims:
Many patients with HCC of Barcelona Clinic Liver Cancer (BCLC) stage A exceeding the Milan criteria, or of BCLC stage B, can undergo resection after successful preoperative therapy, but an optimal approach has not been identified. We investigated preoperative drug-eluting bead transarterial chemoembolization (DEB-TACE) plus sintilimab, in this setting.

Approach and Results:
In this prospective, phase II study (NCT04174781), adults with HCC of BCLC stage A exceeding the Milan criteria, or BCLC stage B, and ineligible for surgical resection, received sintilimab 200 mg and DEB-TACE. The primary endpoint was progression-free survival by modified RECIST. Secondary endpoints included objective response rate, pathologic response rate, and safety. At the data cutoff (July 2022), among 60 patients, the objective response rate was 62% (37/60) and 51 patients had undergone surgery. After a median follow-up of 26.0 months (range, 3.4–31.8), the median progression-free survival was 30.5 months (95% CI: 16.1–not reached). Among patients undergoing surgery, median progression-free survival was not reached and the 12-month progression-free survival rate was 76% (95% CI: 67–91). A pathologic complete response was achieved in 14% (7/51) of these patients. All patients experienced at least one adverse event, but these were generally manageable. Exploratory analyses showed an association between cytokeratin, V-domain Ig-containing Suppressor of T-cell Activation, CD68, CD169, and cluster 13 fibroblasts and recurrence after surgery.

Conclusions.
Sintilimab plus DEB-TACE before surgery showed good efficacy and safety in patients with HCC of BCLC stage A exceeding the Milan criteria or BCLC stage B.
A series of homeopathic remedies-related severe drug-induced liver injury from South India
Authors: Theruvath Arif Hussain , Raveendran Resmi , Philips Cyriac Abby , Ahamed Rizwan , Abduljaleel Jinsha K , Tharakan Ajit , Rajesh Sasidharan , Augustine Philip 
Published: February 2023

Introduction:
Homeopathic remedies are highly diluted formulations without proven clinical benefits, traditionally believed not to cause adverse events. Nonetheless, published literature reveals severe local and non–liver-related systemic side effects. We present the first series on homeopathy-related severe drug-induced liver injury (DILI) from a single center.

Methods:
A retrospective review of records from January 2019 to February 2022 identified 9 patients with liver injury attributed to homeopathic formulations. Competing causes were comprehensively excluded. Chemical analysis was performed on retrieved formulations using triple quadrupole gas chromatography-mass spectrometry and inductively coupled plasma atomic emission spectroscopy.

Results:
Males predominated with a median age of 54 years. The most typical clinical presentation was acute hepatitis, followed by acute on chronic liver failure. All patients developed jaundice, and ascites were notable in one-third of the patients. Five patients had underlying chronic liver disease. COVID-19 prevention was the most common indication for homeopathic use. Probable DILI was seen in 77.8%, and hepatocellular injury predominated (66.7%). Four (44.4%) patients died (3 with chronic liver disease) at a median follow-up of 194 days. Liver histopathology showed necrosis, portal and lobular neutrophilic inflammation, and eosinophilic infiltration with cholestasis. A total of 29 remedies were consumed between 9 patients, and 15 formulations were analyzed. Toxicology revealed industrial solvents, corticosteroids, antibiotics, sedatives, synthetic opioids, heavy metals, and toxic phyto-compounds, even in ‘supposed’ ultra-dilute formulations.

Conclusion:
Homeopathic remedies potentially result in severe liver injury, leading to death in those with underlying liver disease. The use of mother tinctures, insufficient dilution, poor manufacturing practices, adulteration and contamination, and the presence of direct hepatotoxic herbals were the reasons for toxicity. Physicians, the public, and patients must realize that Homeopathic drugs are not ‘gentle placebos.’
Urine as liquid gold: the transcriptional landscape of acute rejection defined by urinary cell mRNA profiling of kidney allograft recipients
Authors: Suthanthiran Manikkam 
Published: February 2023

Purpose of review
Because all functioning nephrons contribute to urine formation, we reasoned that urine would be a suitable substitute to kidney allograft biopsy to discern human kidney allograft status. In view of compelling data that ribonucleic acid (RNA) sequencing outperforms microarray-based profiling, we performed RNA sequencing of urinary cells and kidney allograft biopsies to define the transcriptional landscape of allograft rejection.

Recent findings
Whole genome transcriptome profiling identified unique and shared gene signatures of acute T cell mediated rejection (TCMR) and antibody mediated rejection (AMR). We found that biopsy rejection signatures are enriched in urinary cells and that the immune cellular landscape is more diverse and enriched in urine compared to biopsies. Towards a patient friendly protocol for urinary cell messenger RNA (mRNA) profiling, we developed a filtration-based protocol for the initial processing of urine at home and demonstrated excellent performance characteristics of the filter- based protocol.

Summary
Acute rejection signatures are enriched in urinary cells. Urinary cell mRNA profiles are diagnostic and prognostic of acute rejection and could serve as yardsticks of in-vivo immune status. RNA sequencing yields insights into mechanisms of rejection and helps prioritize therapeutic targets. The filtration protocol for home processing of urine may optimize immune surveillance.
Incidental Adiposis Dolorosa (Dercum’s Disease) Detected on 18F-DCFPyL PET/CT
Authors: Mardasi Ebtesam , Russon Andrew , Mansberg Victor , Bui Chuong , Mansberg Robert 
Published: February 2023

Abstract
A 64-year-old man with recently diagnosed prostate adenocarcinoma and Gleason score 4 + 3 = 7 with a mildly elevated prostate-specific antigen of 5.17 μg/L was referred for 18F-DCFPyL PET/CT for primary staging. The scan demonstrated incidental innumerable moderately avid subcutaneous nodules due to adiposis dolorosa (Dercum’s disease), which is a rare adipose tissue disease.
Superiority of 18F-FDG PET/CT to 68GA-FAPI PET/CT in Adrenocortical Tumor Imaging
Authors: Kaplan İhsan , Can Canan , Kepenek Ferat , Ibiloğlu İbrahim , Güzel Yunus 
Published: February 2023

Abstract

18F-FDG PET/CT was performed to evaluate the response to treatment in a 62-year-old female patient who was operated for adrenocortical carcinoma. High FDG uptake was observed in recurrent lesion in the left adrenal gland site and metastatic lesions. In the 68Ga-FAPI-04 PET/CT study, low FAPI uptake was observed in both recurrences and metastases. In this case, we demonstrated the superiority of 18F-FDG PET/CT over 68Ga-FAPI-04 PET/CT in the evaluation of adrenocortical carcinoma.
Does an Additional Bile Duct Flush With Low-viscosity Preservation Solution Reduce Bile Duct Injury? A Single-blinded Randomized Clinical Trial
Authors: Ly Mark , Lau Ngee-Soon , McKenzie Catriona , Kench James G. , McCaughan Geoffrey , Crawford Michael , Pulitano Carlo 
Published: February 2023

Introduction.
Biliary complications are a common cause of morbidity after liver transplantation and associated with bile duct injury. To reduce injury, a bile duct flush is performed with high-viscosity preservation solution. It has been suggested that an earlier additional bile duct flush with low-viscosity preservation solution may reduce bile duct injury and biliary complications. This study aimed to investigate whether an earlier additional bile duct flush would reduce bile duct injury or biliary complications.

Methods.
A randomized trial was conducted using 64 liver grafts from brain dead donors. The control group received a bile duct flush with University of Wisconsin (UW) solution after donor hepatectomy. The intervention group received a bile duct flush using low-viscosity Marshall solution immediately after the onset of cold ischemia and a bile duct flush with University of Wisconsin solution after donor hepatectomy. The primary outcomes were the degree of histological bile duct injury, assessed using the bile duct injury score, and biliary complications within 24 mo of transplant.

Results.
Bile duct injury scores were not different between the 2 groups. Similar rates of biliary complications occurred in the intervention group (31% [n = 9]) and controls (23% [n = 8]) (P = 0.573). No difference between groups was observed for anastomotic strictures (24% versus 20%, P = 0.766) or nonanastomotic strictures (7% versus 6%, P = 1.00).

Conclusions.
This is the first randomized trial to investigate an additional bile duct flush using low-viscosity preservation solution during organ procurement. The findings from this study suggest that performing an earlier additional bile duct flush with Marshall solution does not prevent biliary complications and bile duct injury.
Three-year Outcomes After Conversion From Monthly to Every 2-month Belatacept Maintenance Therapy in Kidney Transplant Recipients: Results From a Randomized Controlled Trial
Authors: Johnson Aileen C. , Karadkhele Geeta M. , Shenvi Neeta , Easley Kirk A. , Larsen Christian P. , Badell I. Raul 
Published: February 2023

Background.
Maintenance immunosuppression with belatacept following kidney transplantation results in improved long-term graft function as compared with calcineurin inhibitors. However, broad application of belatacept has been limited, in part related to logistical barriers surrounding a monthly (q1m) infusion requirement.

Methods.
To determine whether every 2-mo (q2m) belatacept is noninferior to standard q1m maintenance, we conducted a prospective, single-center randomized trial in low-immunologic-risk, stable renal transplant recipients. Here, post hoc analysis of 3-y outcomes, including renal function and adverse events, are reported.

Results.
One hundred sixty-three patients received treatment in the q1m control group (n = 82) or q2m study group (n = 81). Renal allograft function as measured by baseline-adjusted estimated glomerular filtration rate was not significantly different between groups (time-averaged mean difference of 0.2 mL/min/1.73 m2; 95% confidence interval: −2.5, 2.9). There were no statistically significant differences in time to death or graft loss, freedom from rejection, or freedom from donor-specific antibodies (DSAs). During the extended 12- to 36-mo follow-up, 3 deaths, 1 graft loss occurred in the q1m group, compared with 2 deaths, and 2 graft losses in the q2m group. In the q1m group, 1 patient developed DSAs and acute rejection. In the q2m group, 3 patients developed DSAs and 2 associated with acute rejection.

Conclusions.
Based on the similar renal function and survival at 36 mo compared with q1m, q2m belatacept is a potentially viable maintenance immunosuppressive strategy in low immunologic risk kidney transplant recipients that may facilitate increased clinical utilization of costimulation blockade-based immunosuppression.
Maintenance and transformation of representational formats during working memory prioritization
Authors: Estefan Daniel Pacheco , Fellner Marie Christin , Kunz Lukas , Zhang Hui , Reinacher Peter , Roy Charlotte , Brandt Armin , Schulze-Bonhage Andreas , Yang Linglin , Wang Shuang , Liu Jing , Xue Gui , Axmacher Nikolai 
Published: February 2023

AbstractVisual working memory depends on both material-specific brain areas in the ventral visual stream (VVS) that support the maintenance of stimulus representations and on regions in prefrontal cortex (PFC) that control these representations. Recent studies identified stimulus-specific working memory contents via representational similarity analysis (RSA) and analyzed their representational format using deep neural networks (DNNs) as models of the multi-layered hierarchy of information processing. How executive control prioritizes relevant working memory contents and whether this affects their representational formats remains an open question, however. Here, we addressed this issue using a multi-item working memory task involving a retro-cue that prompted participants to maintain one particular item. We exploited the excellent spatiotemporal resolution of intracranial EEG (iEEG) recordings in epilepsy patients and analyzed activity at electrodes in VVS (n=28 patients) and PFC (n=16 patients). During encoding, we identified category-specific information in both VVS and PFC. During maintenance, this information re-occurred in VVS but not in the PFC – suggesting a transformation of PFC representations from encoding to maintenance which putatively reflects the prioritization process. We thus applied RSA in combination with different DNN architectures to investigate the representational format of prioritized working memory contents. Representations during the maintenance period matched representations in deep layers of recurrent but not feedforward DNNs, in both VVS and PFC. While recurrent DNN representations matched PFC representations in the beta band following the retro-cue, they corresponded to VVS representations in a lower theta-alpha frequency range (3-14Hz) towards the end of the maintenance period. Findings could be replicated in recurrent DNNs with two different architectures and using two different training sets. Together, these results demonstrate that VWM relies on representational transformations in VVS and PFC that give rise to distinct coding schemes of prioritized contents.
Photosynthetic response ofChara brauniitowards different bicarbonate concentrations
Authors: Heise Carolin Magdalene , Hagemann Martin , Schubert Hendrik 
Published: February 2023

AbstractA variety of inorganic carbon acquisition modes have been proposed in Characean algae, however, the specific inorganic carbon uptake mechanism is unknown for the genusChara. In the present study, we analyzed ifC. brauniican efficiently use HCO3-as a carbon source for photosynthesis. For this purpose,C. brauniiwas exposed to different concentrations of NaHCO3-for different time scales. The photosynthetic electron transport through photosystem I (PSI) and II (PSII), the maximal electron transport rate (ETRmax), the efficiency of the electron transport rate (α, the initial slope of the ETR), and the light saturation point of photosynthesis (Ek) were evaluated. Additionally, pigment contents (chlorophylla, chlorophyllb, and carotenoids) were determined. Bicarbonate addition positively affected ETRmaxafter direct HCO3-application of both PSII and PSI, but this effect decreased after 1 h and 24 h. Similar trends were seen forEk, but no significant effect was observed for α. Pigment contents showed no significant changes in relation to different HCO3-concentrations. To evaluate if cyclic electron flow around PSI was involved in active HCO3-uptake, the ratio of PSI ETRmax/PSII ETRmaxwas calculated but did not show a distinctive trend. These results suggest thatC. brauniican utilize NaHCO3-in short time periods as a carbon source but relies on other carbon acquisition mechanisms over prolonged time periods. These observations differentiateC. brauniifrom other examinedCharaspp. and suggest a minor direct role of HCO3-as a carbon source for photosynthesis in this alga.
A Multi-omic and Multi-Species Analysis of Right Ventricular Failure
Authors: Mendelson Jenna B. , Sternbach Jacob D. , Doyle Michelle J. , Mills Lauren , Hartweck Lynn M. , Tollison Walt , Carney John P. , Lahti Matthew T. , Bianco Richard W. , Kalra Rajat , Kazmirczak Felipe , Hindmarch Charles , Archer Stephen L , Prins Kurt W. , Martin Cindy M. 
Published: February 2023

AbstractRight ventricular failure (RVF) is a leading cause of morbidity and mortality in multiple cardiovascular diseases, but there are no approved treatments for RVF as therapeutic targets are not clearly defined. Contemporary transcriptomic/proteomic evaluations of RVF are predominately conducted in small animal studies, and data from large animal models are sparse. Moreover, a comparison of the molecular mediators of RVF across species is lacking. Here, we used transcriptomics and proteomics analyses to define the molecular pathways associated with cardiac MRI-derived values of RV hypertrophy, dilation, and dysfunction in pulmonary artery banded (PAB) piglets. Publicly available data from rat monocrotaline-induced RVF and pulmonary arterial hypertension patients with preserved or impaired RV function were used to compare the three species.Transcriptomic and proteomic analyses identified multiple pathways that were associated with RV dysfunction and remodeling in PAB pigs. Surprisingly, disruptions in fatty acid oxidation (FAO) and electron transport chain (ETC) proteins were different across the three species. FAO and ETC proteins and transcripts were mostly downregulated in rats, but were predominately upregulated in PAB pigs, which more closely matched the human data. Thus, the pig PAB metabolic molecular signature was more similar to human RVF than rodents. These data suggest there may be divergent molecular responses of RVF across species, and that pigs more accurately recapitulate the metabolic aspects of human RVF.
The density of doublecortin cells in the piriform cortex is affected by transition to adulthood but not first pregnancy in female mice
Authors: Esteve-Pérez Rafael , Abellán-Álvaro María , Navarro-Moreno Cinta , Prina Michele , Barneo-Muñoz Manuela , Lanuza Enrique , Sánchez-Catalán María José , Martínez-García Fernando , Torres-Pérez Jose Vicente , Agustín-Pavón Carmen 
Published: February 2023

AbstractMotherhood is a critical period modulating behavioural changes to favour survival in mammals. In mice, olfaction is a key driver of social behaviours, and adult neurogenesis in the olfactory bulb is modulated at this stage, contributing to pup recognition. However, whether motherhood would also promote changes in the population of immature neurons of the piriform cortex is unknown. To investigate this question, we analysed the expression of doublecortin (DCX), a marker of immature neurons, in prepubescentvsyoung adults, in virginvspregnant and in pup-sensitized virginsvslactating female mice. We found that the density of DCX cells sharply decreased in the piriform cortex with age, but pregnancy and lactation failed to significantly alter the density of these cells. To further analyse how motherhood could affect DCX-ir cells, we co-labelled DCX cells with NeuN, an archetypical marker of mature neurons. We did not find significant differences in the percentage of double-labelled cells nor in features related to maturation like number of neurites or main diameter in lactating dams as compared to pup-sensitized virgin females. Our results suggest that the first pregnancy does not significantly affect the differentiation of immature neurons of the piriform cortex.
Temporal control by co-factors prevents kinetic trapping in retroviral Gag lattice assembly
Authors: Qian Yian , Evans Daniel , Mishra Bhavya , Fu Yiben , Liu Zixiu Hugh , Guo Sikao , Johnson Margaret E. 
Published: February 2023

AbstractFor retroviruses like HIV to proliferate, they must form virions shaped by the self-assembly of Gag polyproteins into a rigid lattice. This immature Gag lattice has been structurally characterized and reconstitutedin vitro, revealing the sensitivity of lattice assembly to multiple co-factors. Due to this sensitivity, the energetic criterion for forming stable lattices is unknown, as are their corresponding rates. Here, we use a reaction-diffusion model designed from the cryo-ET structure of the immature Gag lattice to map a phase diagram of assembly outcomes controlled by experimentally constrained rates and free energies, over experimentally relevant timescales. We find that productive assembly of complete lattices in bulk solution is extraordinarily difficult due to the large size of this ∼3700 monomer complex. Multiple Gag lattices nucleate before growth can complete, resulting in loss of free monomers and frequent kinetic trapping. We therefore derive a time-dependent protocol to titrate or ‘activate’ the Gag monomers slowly within the solution volume, mimicking the biological roles of co-factors. This general strategy works remarkably well, yielding productive growth of self-assembled lattices for multiple interaction strengths and binding rates. By comparing to thein vitroassembly kinetics, we can estimate bounds on rates of Gag binding to Gag and the cellular co-factor IP6. Our results show that Gag binding to IP6 can provide the additional time-delay necessary to support smooth growth of the immature lattice with relatively fast assembly kinetics, mostly avoiding kinetic traps. Our work provides a foundation for predicting and disrupting formation of the immature Gag lattice via targeting specific protein- protein binding interactions.
Accurate and Efficient Estimation of Local Heritability using Summary Statistics and LD Matrix
Authors: Li Hui , Mazumder Rahul , Lin Xihong 
Published: February 2023

ABSTRACTExisting SNP-heritability estimation methods that leverage GWAS summary statistics produce estimators that are less efficient than the restricted maximum likelihood (REML) estimator using individual-level data under linear mixed models (LMMs). Increasing the precision of a heritability estimator is particularly important for regional analyses, as local genetic variances tend to be small. We introduce a new estimator for local heritability, “HEELS”, which attains comparable statistical efficiency as REML (i.e. relative efficiency greater than 92%) but only requires summary-level statistics – Z-scores from the marginal association tests plus the empirical LD matrix. HEELS significantly improves the statistical efficiency of the existing summary-statistics-based heritability estimators– for instance, HEELS produces heritability estimates that are more than 3-fold and 7-times less variable than GRE and LDSC, respectively. Moreover, we introduce a unified framework to evaluate and compare the performance of different LD approximation strategies. We propose representing the empirical LD as the sum of a low-rank matrix and a banded matrix. This approximation not only reduces the storage and memory cost of using the LD matrix, but also improves the computational efficiency of the HEELS estimation. We demonstrate the statistical efficiency of HEELS and the advantages of our proposed LD approximation strategies both in simulations and through empirical analyses of the UK Biobank data.