bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Prospective, Single-Arm Study to Evaluate the Safety and Efficacy of RD2-Ver.02, an Autologous Blood Clot, in the Treatment of Anal Fistula
Authors: Ram Edward , Zager Yaniv , Carter Dan , Saukhat Olga , Anteby Roi , Nachmany Ido , Horesh Nir 
Published: December 2023

BACKGROUND:
Surgical treatment of complex perianal fistula is technically challenging, associated with risk of failure, and may require multiple procedures. In recent years, several biologic agents have been developed for the purpose of permanently eradicating anal fistulous disease with variable success. RD2-Ver.02 treatment is an autologous whole blood product created from the patients’ blood, which forms a provisional matrix that was found to be safe and effective in healing acute and chronic cutaneous wounds.

OBJECTIVE:
To assess the efficacy and safety of RD2-Ver.02 as a treatment for transsphincteric perianal fistulas.

DESIGN:
A prospective single-arm study.

SETTINGS:
A single tertiary medical center.

PATIENTS:
Patients with simple or complex transsphincteric fistulas confirmed by magnetic resonance imaging were included in the study. Etiology was either cryptoglandular or Crohn’s related (in the absence of active luminal bowel disease).

INTERVENTION:
The outpatient procedure was performed under general anesthesia and consisted of: 1) physical debridement and cleansing of the fistula tract; 2) suture closure of the internal opening; and 3) instillation of RD2-Ver.02 into the entire tract.

MAIN OUTCOME MEASURES:
Safety and efficacy at 6- and 12-months following surgery.

RESULTS:
Fifty-three patients (77% male) with a median age of 42 (20-72) years were included in the study. Three patients withdrew consent, and 1 patient was lost to follow-up. At the time of this interim analysis, 49 and 33 patients completed the 6 and 12 months follow-up period, respectively. Thirty-four (34) patients achieved complete healing (69%) at 6 months while 20 patients out of 33 (60%) achieved healing after 1 year. All patients who achieved healing at 6 months remained healed at the 1 year mark. In a subgroup analysis of Crohn’s patients, 7 of 9 patients completed 1-year follow-up, with 5 patients (71%) achieving clinical remission. No major side effects or postoperative complications were noted, while 2 adverse events occurred (admission for pain control and COVID-19 infection).

LIMITATIONS:
Noncomparative single-arm pilot study.

CONCLUSIONS:
Treatment with RD2-Ver.02 in perianal fistular disease was found to be feasible and safe, with an acceptable healing rate in both cryptoglandular and Crohn’s fistula in ano. Further comparative assessment is required to determine its potential role in the treatment paradigm of fistula-in-ano. See Video Abstract.
Effects of Wuzhi Capsule on Whole-Blood Tacrolimus Concentration Levels: A Systematic Review and Meta-Analysis
Authors: Zhang Chunyan , Ren Xiaolei , Liu Yi , Huang Lin , Feng Yufei , Zhang Xiaohong 
Published: December 2023

Background:
Wuzhi Capsule (WZC) is a traditional Chinese medicinal herb widely used to treat drug-induced hepatitis or liver dysfunction and is usually prescribed in China to increase tacrolimus concentration. Several studies with small sample sizes have shown that WZC can increase tacrolimus concentration levels in clinical practice. This study aimed to evaluate the effect of WZC on whole-blood tacrolimus concentration levels and safety.

Methods:
We searched 7 databases for randomized clinical trials (RCTs) and observational studies (OSs) comparing whole-blood tacrolimus concentration levels between WZC and non-WZC treatments. Data analysis was performed using Review Manager version 5.3. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines.

Results:
Eleven studies involving 6 RCTs and 5 OSs were included. The meta-analysis indicated that whole-blood tacrolimus concentration levels in the WZC group was significantly higher than that of the non-WZC group [weighted mean difference = 1.38, 95% CI (confidence interval), 1.21–1.56, P < 0.001], and similar results were shown in all the subgroups of follow-up time, different primary disease, and different WZC doses. In the self-control OSs, the whole-blood tacrolimus concentration levels in the WZC group was significantly higher than the non-WZC group (weighted mean difference = 1.17, 95% CI, 0.71–1.64, P < 0.001). WZC was generally well tolerated and there was no significant difference in the incidence of adverse reactions between the 2 groups.

Conclusions:
WZC can increase whole-blood tacrolimus concentration levels. This may be an economical and practical treatment choice for patients, especially those with poor oral tacrolimus absorption capabilities. Nevertheless, RCTs and OSs with large sample sizes and high quality are needed in the future to confirm these positive results.
Fluorescein Angiography Evaluation of Children Previously Treated with Anti-VEGF Monotherapy for Retinopathy of Prematurity
Authors: Karademir Fatma Poslu , Vural Aslı , Özbaş Mehmet , Demirayak Bengi 
Published: December 2023

Purpose:
To determine the level of vascularization and peripheral vascular findings by fluorescence angiography (FA) in patients with aggressive retinopathy of prematurity (A-ROP) or type 1 retinopathy of prematurity (ROP) treated with a single dose of anti-vascular endothelial growth factor (VEGF).

Methods:
Data of patients referred to our clinic for FA examination between June 2016 and September 2021 were retrospectively analyzed. Patients who had their first FA examination at the age of 1 year or older were included in the study.

Results:
A total of 486 eyes of 250 patients were included. Of these, 83 eyes (17.1%) had vascular termination in zone II and 403 eyes (82.9%) in zone III. In 62.7% of eyes, the distance from the vascular terminals to the temporal ora serrata was less than 2 disc diameters (DD) and in 20.2% it was more than 2 DD. Abnormal vascular findings were noted, including circumferential vessels (41.2%), finger-like projection anomaly (36.2%), hyperfluorescence (16.9%), fine branching and blunt termination (15%), and arteriovenous shunt (9.9%).

Conclusion:
FA performed late in the course of treatment can clearly define the vascular termini and detect abnormalities that cannot be detected by indirect ophthalmoscopy. Follow-up with FA can help prevent complications that can lead to vision loss.
Neighborhood Perceptions Are Associated With Intrinsic Amygdala Activity and Resting-State Connectivity With Salience Network Nodes Among Older Adults
Authors: Ortiz-Whittingham Lola R. , Zhan Liang , Ortiz-Chaparro Erika N. , Baumer Yvonne , Zenk Shannon , Lamar Melissa , Powell-Wiley Tiffany M. 
Published: December 2023

ABSTRACT

Objective
Neighborhood perceptions are associated with physical and mental health outcomes; however, the biological associates of this relationship remain to be fully understood. Here, we evaluate the relationship between neighborhood perceptions and amygdala activity and connectivity with salience network (i.e., insula, anterior cingulate, thalamus) nodes.

Methods
Forty-eight older adults (mean age = 68 [7] years, 52% female, 47% non-Hispanic Black, 2% Hispanic) without dementia or depression completed the Perceptions of Neighborhood Environment Scale. Lower scores indicated less favorable perceptions of aesthetic quality, walking environment, availability of healthy food, safety, violence (i.e., more perceived violence), social cohesion, and participation in activities with neighbors. Participants separately underwent resting-state functional magnetic resonance imaging.

Results
Less favorable perceived safety (β = −0.33, p
FDR = .04) and participation in activities with neighbors (β = −0.35, p
FDR = .02) were associated with higher left amygdala activity, independent of covariates including psychosocial factors. Less favorable safety perceptions were also associated with enhanced left amygdala functional connectivity with the bilateral insular cortices and the left anterior insula (β = −0.34, p
FDR = .04). Less favorable perceived social cohesion was associated with enhanced left amygdala functional connectivity with the right thalamus (β = −0.42, p
FDR = .04), and less favorable perceptions about healthy food availability were associated with enhanced left amygdala functional connectivity with the bilateral anterior insula (right: β = −0.39, p
FDR = .04; left: β = −0.42, p
FDR = .02) and anterior cingulate gyrus (β = −0.37, p
FDR = .04).

Conclusions
Taken together, our findings document relationships between select neighborhood perceptions and amygdala activity as well as connectivity with salience network nodes; if confirmed, targeted community-level interventions and existing community strengths may promote brain-behavior relationships.
ENDOCANNABINOID SYSTEM IN THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS MODULATES AUTONOMIC AND CARDIOVASCULAR CHANGES BUT NOT VASOPRESSIN RESPONSE IN A RAT HEMORRHAGIC SHOCK MODEL
Authors: Busnardo Cristiane , Fassini Aline , Lopes-Azevedo Silvana , Omena-Giatti Luana , Goulart Melissa T. , Antunes-Rodrigues José , Alves Fernando H.F. , Corrêa Fernando M.A. , Crestani Carlos C. 
Published: December 2023

ABSTRACT
We evaluated the participation of the endocannabinoid system in the paraventricular nucleus of the hypothalamus (PVN) on the cardiovascular, autonomic, and plasma vasopressin (AVP) responses evoked by hemorrhagic shock in rats. For this, the PVN was bilaterally treated with either vehicle, the selective cannabinoid receptor type 1 antagonist AM251, the selective fatty acid amide hydrolase amide enzyme inhibitor URB597, the selective monoacylglycerol-lipase enzyme inhibitor JZL184, or the selective transient receptor potential vanilloid type 1 antagonist capsazepine. We evaluated changes on arterial pressure, heart rate, tail skin temperature (ST), and plasma AVP responses induced by bleeding, which started 10 min after PVN treatment. We observed that bilateral microinjection of AM251 into the PVN reduced the hypotension during the hemorrhage and prevented the return of blood pressure to baseline values in the posthemorrhagic period. Inhibition of local 2-arachidonoylglycerol metabolism by PVN treatment with JZL184 induced similar effects in relation to those observed in AM251-treated animals. Inhibition of local anandamide metabolism via PVN treatment with URB597 decreased the depressor effect and ST drop induced by the hemorrhagic stimulus. Bilateral microinjection of capsazepine mitigated the fall in blood pressure and ST. None of the PVN treatments altered the increased plasma concentration of AVP and tachycardia induced by hemorrhage. Taken together, present results suggest that endocannabinoid neurotransmission within the PVN plays a prominent role in cardiovascular and autonomic, but not neuroendocrine, responses evoked by hemorrhage.
REVIEWING THE DYSREGULATION OF ADAMTS13 AND VWF IN SEPSIS
Authors: Madarati Hasam , Singh Kanwal , Sparring Taylor , Andrisani Peter , Liaw Patricia C. , Fox-Robichaud Alison E. , Kretz Colin A. 
Published: December 2023

ABSTRACT
Sepsis is defined as a life-threatening organ dysfunction caused by excessive host response to infection, and represents the most common cause of in-hospital deaths. Sepsis accounts for 30% of all critically ill patients in the intensive care unit (ICU), and has a global mortality rate of 20%. Activation of blood coagulation during sepsis and septic shock can lead to disseminated intravascular coagulation, which is characterized by microvascular thrombosis. Von Willebrand factor (VWF) and ADAMTS13 are two important regulators of blood coagulation that may be important links between sepsis and mortality in the ICU. Herein we review our current understanding of VWF and ADAMTS13 in sepsis and other critical illnesses and discuss their contribution to disease pathophysiology, their use as markers of severe illness, and potential targets for new therapeutic development.
Role of microglia in sepsis-associated encephalopathy pathogenesis: an update
Authors: Yu Zhijie , Shi Hui , Zhang Jingjing , Ma Chunhan , He Chen , Yang Fei , Zhao Lina 
Published: December 2023

Abstract
Sepsis-associated encephalopathy (SAE) is a serious complication of sepsis, which is characterized by cognitive dysfunction, a poor prognosis, and high incidences of morbidity and mortality. Substantial levels of systemic inflammatory factors induce neuroinflammatory responses during sepsis, ultimately disrupting the central nervous system's (CNS) homeostasis. This disruption results in brain dysfunction through various underlying mechanisms, contributing further to SAE’s development. Microglia, the most important macrophage in the CNS, can induce neuroinflammatory responses, brain tissue injury, and neuronal dysregulation, resulting in brain dysfunction. They serve an important regulatory role in CNS homeostasis and can be activated through multiple pathways. Consequently, activated microglia are involved in several pathogenic mechanisms related to SAE and play a crucial role in its development. This article discusses the role of microglia in neuroinflammation, dysfunction of neurotransmitters, disruption of the blood-brain barrier (BBB), abnormal control of cerebral blood flow, mitochondrial dysfunction, and reduction in the number of good bacteria in the gut as main pathogenic mechanisms of SAE, and focuses on studies targeting microglia to ameliorate SAE to provide a theoretical basis for targeted microglial therapy for SAE.
Progressive Reduction in Preventable Mortality in a State Trauma System Using Continuous Preventable Mortality Review to Drive Provider Education: Results of Analyzing 1,979 Trauma Deaths from 2015 to 2022
Authors: Mabry Charles D , Davis Benjamin , Sutherland Michael , Robertson Ronald , Carger Jennifer , Wyrick Deidre , Collins Terry , Porter Austin , Kalkwarf Kyle 
Published: December 2023

BACKGROUND:
The state legislature codified and funded the Arkansas Trauma System (ATS) in 2009. Quarterly preventable mortality reviews (PMRs) by the ATS began in 2015 and were used to guide state-wide targeted education to reduce preventable or potentially preventable (P/PP) deaths. We present the results of this PMR-education initiative from 2015 to 2022.

STUDY DESIGN:
The ATS uses a statistical sampling model of the Arkansas Trauma Registry to select ~40% of the deaths for quarterly review, reflecting the overall the Arkansas Trauma Registry mortality population. A multispecialty PMR committee reviews the medical records from prehospital care to death, and hospital and regional advisory council reviews for each death. The PMR committee assigns opportunities for improvement (OFIs), cause(s) of death, and the likelihood of preventability for each case. Education to improve trauma care includes annual state-wide trauma meetings, novel classes targeted at level III/IV trauma center hospital providers, trauma evidence–based guidelines, and PMR “pearls.”

RESULTS:
We reviewed 1,979 deaths with 211 (10.6%) deaths judged to be P/PP deaths. There was a progressive decrease in P/PP deaths and OFIs for P/PP deaths. Five OFI types targeted by education accounted for 72% of the 24 possible OFI types in the P/PP cases, and 94% of the “contributory OFIs.” Reductions in “delay in treatment” resulted in the most rapid decrease in P/PP deaths.

CONCLUSIONS:
Using ongoing PMR studies to target provider education led to a reduction in P/PP deaths and OFIs for P/PP deaths. Focusing on education designed to improve preventable mortality can result in a substantial decrease in P/PP deaths by 43% (14% to 8%) for trauma systems.
Association between the oral microbiome and brain resting state connectivity in schizophrenia
Authors: Lin Dongdong , Fu Zening , Liu Jingyu , Perrone-Bizzozero Nora , Hutchison Kent E. , Bustillo Juan , Du Yuhui , Pearlson Godfrey , Calhoun Vince D. 
Published: December 2023

AbstractRecent microbiome-brain axis findings have shown evidence of the modulation of microbiome community as an environmental mediator in brain function and psychiatric illness. This work is focused on the role of the microbiome in understanding a rarely investigated environmental involvement in schizophrenia (SZ), especially in relation to brain circuit dysfunction. We leveraged high throughput microbial 16s rRNA sequencing and functional neuroimaging techniques to enable the delineation of microbiome-brain network links in SZ. N=213 SZ and healthy control (HC) subjects were assessed for the oral microbiome. Among them, 139 subjects were scanned by resting-state functional magnetic resonance imaging (rsfMRI) to derive brain functional connectivity. We found a significant microbiome compositional shift in SZ beta diversity (weighted UniFrac distance, p= 6×10−3; Bray-Curtis distance p = 0.021). Fourteen microbial species involving pro-inflammatory and neurotransmitter signaling and H2S production, showed significant abundance alterations in SZ. Multivariate analysis revealed one pair of microbial and functional connectivity components showing a significant correlation of 0.46. Thirty five percent of microbial species and 87.8% of brain functional network connectivity from each component also showed significant differences between SZ and HC with strong performance in classifying SZ from HC, with an area under curve (AUC) = 0.84 and 0.87, respectively. The results suggest a potential link between oral microbiome dysbiosis and brain functional connectivity alteration in relation to SZ, possibly through immunological and neurotransmitter signaling pathways and the hypothalamic-pituitary-adrenal axis, supporting for future work in characterizing the role of oral microbiome in mediating effects on SZ brain functional activity.
SEAD: an augmented reference panel with 22,134 haplotypes boosts the rare variants imputation and GWAS analysis in Asian population
Authors: Yang Meng-Yuan , Zhong Jia-Dong , Li Xin , Tian Geng , Bai Wei-Yang , Fang Yi-Hu , Qiu Mo-Chang , Yuan Cheng-Da , Yu Chun-Fu , Li Nan , Yang Ji-Jian , Liu Yu-Heng , Yu Shi-Hui , Zhao Wei-Wei , Liu Jun-Quan , Sun Yi , Cong Pei-Kuan , Khederzadeh Saber , Zhao Pian-Pian , Qian Yu , Guan Peng-Lin , Gu Jia-Xuan , Gai Si-Rui , Yi Xiang-Jiao , Tao Jian-Guo , Chen Xiang , Miao Mao-Mao , Lei Lan-Xin , Xu Lin , Xie Shu-Yang , Li Jin-Chen , Guo Ji-Feng , Karasik David , Yang Liu , Tang Bei-Sha , Huang Fei , Zheng Hou-Feng 
Published: December 2023

AbstractHere, we present theSouth andEastAsian referenceDatabase (SEAD) panel (https://imputationserver.westlake.edu.cn/), which comprises whole genome sequencing data from 11,067 individuals across 17 countries in Asia. The SEAD panel, which excludes singleton variants, consists of 22,134 haplotypes and 88,294,957 variants. The SEAD panel demonstrated higher accuracy compared to 1kGP, TOPMed and ChinaMAP in South Asian population. And as the proportion of South Asian ancestry increased, the proportion of low-frequency and rare well-imputed variants imputed using the SEAD panel progressively increased, whereas those imputed with TOPMed panel significantly decreased. Additionally, when imputing the East Asian population, the SEAD showed comparable concordance in imputation with ChinaMAP panel, while the TOPMed panel was inferior. Finally, we applied the augmented SEAD panel to conduct a discovery and replication genome-wide association study (GWAS) for hip and femoral neck (FN) bone mineral density (BMD) traits within the 5,369 Westlake BioBank for Chinese (WBBC) genotyped samples. The single-variant test suggests that rare variants nearSNTG1gene are associated with hip BMD (rs60103302, MAF=0.0092,P=1.67×10−7). The variant-set analysis also suggests the association of this gene (Pslide_window=9.08×10−9,Pgene_centric=5.27×10−8). The gene and variants achieved a suggestive level for FN BMD. This gene was not reported previously and can only be detected by using Asian reference panel. The preliminary experiment in-vitro demonstrated that the identified rare variant could upregulate theSNTG1expression, which in turn inhibits the proliferation and differentiation of preosteoblast.
Evaluating HIV-1 Infectivity and Virion Maturation Across Varied Producer Cells with a Novel FRET-Based Detection and Quantification Assay
Authors: McGraw Aidan , Hillmer Grace , Choi Jeongpill , Narayan Kedhar , Marquez Dacia , Tibebe Hasset , Izumi Taisuke 
Published: December 2023

AbstractThe maturation of HIV-1 virions is a crucial process in viral replication. Although T cells are a primary source of virus production, much of our understanding of virion maturation comes from studies using the HEK293T human embryonic kidney cell line. Notably, there is a lack of comparative analyses between T cells and HEK293T cells in terms of virion maturation efficiency in existing literature. We previously developed an advanced virion visualization system based on the FRET principle, enabling the effective distinction between immature and mature virions via fluorescence microscopy. In this study, we utilized pseudotyped, single-round infectious viruses tagged with FRET labels (HIV-1 Gag-iFRETΔEnv) derived from Jurkat (a human T lymphocyte cell line) and HEK293T cells to evaluate their virion maturation rates. HEK293T-derived virions demonstrated a maturity rate of 81.79%, consistent with other studies and our previous findings. However, virions originating from Jurkat cells demonstrated a significantly reduced maturation rate of 68.67% (p < 0.0001). Correspondingly, viruses produced from Jurkat cells exhibited significantly reduced infectivity compared to those derived from HEK293T cells, with the relative infectivity measured at 65.3%. This finding is consistent with the observed relative maturation rate of viruses produced by Jurkat cells. These findings suggest that initiation of virion maturation directly correlates with viral infectivity. Our observation highlights the dynamic nature of virus-host interactions and their implications for virion production and infectivity.
TMEM41B is an endoplasmic reticulum Ca2+release channel maintaining T cell metabolic quiescence and responsiveness
Authors: Ma Yuying , Wang Yi , Zhao Xiaocui , Jin Gang , Xu Jing , Li Zhuoyang , Yin Na , Gao Zhaobing , Xia Bingqing , Peng Min 
Published: December 2023

SUMMARYNaive T cells are metabolically quiescent. Here, we report an unexpected role of endoplasmic reticulum (ER) Ca2+in preserving T cell metabolic quiescence. TMEM41B, an ER-resident membrane protein previously known for its crucial roles in autophagy, lipid scrabbling and viral infections, is identified as a novel type of concentration-dependent ER Ca2+release channel. Ablation of TMEM41B induces ER Ca2+overload, triggering the upregulation of IL-2 and IL-7 receptors in naive T cells. Consequently, this leads to increased basal signaling of the JAK-STAT, AKT-mTOR, and MAPK pathways, propelling TMEM41B-deficient naive T cells into a metabolically activated yet immunologically naive state. ER Ca2+overload also downregulates CD5, a suppressor of TCR signaling, thereby reducing the activation threshold of TMEM41B-deficient T cells, resulting in attenuated tolerance and heightened T cell responses during infections. In summary, TMEM41B-mediated ER Ca2+release is a pivotal determinant governing metabolic quiescence and responsiveness of naive T cells.