bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network pharmacology explores the mechanisms of Eucommia ulmoides cortex against postmenopausal osteoporosis
Authors: Shao Yan , Chen Song , Zhou Ke , Gan Kaifeng , Li Jin , Xia Chenjie 
Published: May 2022

Abstract
Postmenopausal osteoporosis (PMOP) has become one of most frequent chronic disease worldwide with aging population. Eucommia ulmoides cortex (EU), a traditional Chinese medicine, has long since been used to treat PMOP. The aim of this study is to explore pharmacological mechanisms of EU against PMOP through using network pharmacology approach.
The active ingredients of EU were obtained from Traditional Chinese Medicine System Pharmacology database, and target fishing was performed on these ingredients in UniProt database for identification of their relative targets. Then, we screened the targets of PMOP using GeneCards database and DisGeNET database. The overlapping genes between PMOP and EU were obtained to performed protein–protein interaction, Gene Ontology analysis, Kyoto encyclopedia of genes, and genomes analysis.
Twenty-eight active ingredients were identified in EU, and corresponded to 207 targets. Also, 292 targets were closely associated with PMOP, and 50 of them matched with the targets of EU were considered as therapeutically relevant. Gene ontology enrichment analysis suggested that EU exerted anti-PMOP effects via modulating multiple biological processes including cell proliferation, angiogenesis, and inflammatory response. Kyoto encyclopedia of genes and genomes enrichment analysis revealed several pathways, such as PI3K-AKT pathway, mitogen-activated protein kinase pathway, hypoxia-inducible factors-1 pathway, tumor necrosis factor pathway, and interleukin-17 pathway that might be involved in regulating the above biological processes.
Through the method of network pharmacology, we systematically investigated the mechanisms of EU against PMOP. The multi-targets and multi-pathways identified here could provide new insights for further determination of more exact mechanisms of EU.
Postoperative early and proactive grip strength training program for distal radius fractures promotes earlier recovery of grip strength
Authors: Kaji Yoshio , Yamaguchi Konosuke , Nomura Yumi , Oka Kunihiko , Nakamura Osamu , Ishibashi Yoichi , Yamamoto Tetsuji 
Published: May 2022

Abstract
The use of volar locking plates (VLPs) for distal radius fractures has remarkably improved clinical outcomes; however, there are some reports of delayed recovery of grip strength. Since January 2019, we have been conducting an early and proactive grip strength training program (EGTP). In this program, 20 minutes of grip strength training—using a gripper with a load of 0.7 kg—was initiated from 2 weeks after surgery; the load was then gradually increased. From 6 weeks postsurgery, daily home grip strength training was performed using a gripper with a load of 5 kg, provided to the patient.
We investigated whether the introduction of the EGTP could lead to earlier recovery of grip strength. We also examined whether the EGTP caused postoperative correction loss at the fractured site, or contributed to the early improvement of wrist function.
Thirty-nine patients who underwent surgery using VLPs for distal radius fractures were included in this study; 20 followed the EGTP (EGTP group) and 19 patients did not (NGTP group). For these patients, grip strength and range of motion of the wrist joint were evaluated both 3 and 6 months postoperatively. The Quick Disabilities of the Arm, Shoulder, and Hand (qDASH) scores were also evaluated 6 months postoperatively. Additionally, corrective losses of radial inclination (RI), palmar tilt (PT), and ulnar variance (UV)—occurring from immediately postsurgery to 6 months after surgery—were evaluated.
At both 3 and 6 months postoperatively, the grip strength of the EGTP group was significantly higher than that of the NGTP group. Regarding range of motion, only palmar flexion was significantly improved in the EGTP group at 3 months postoperatively. Conversely, no differences in corrective losses of RI, PT, and UV, or in qDASH scores, were observed between the two groups.
The results of this study suggest that the EGTP can provide early recovery of grip strength and palmar flexion of the wrist without causing corrective loss at the fracture site.
Survival and clinicopathological characteristics of cT4b oral squamous cell carcinoma based on different treatment modalities
Authors: Lin Nan-Chin , Hsu Jui-Ting , Chen Michael Y.C. , Tsai Kuo-Yang 
Published: May 2022

Abstract

Introduction:
Primary surgical treatment for oral squamous cell carcinoma (OSCC) is reserved for T1 to T4a tumors, but not for T4b tumors, according to the present National Comprehensive Cancer Network clinical practice guidelines. In this retrospective study, we aimed to determine the association between the clinicopathological characteristics and different treatment modalities for T4b OSCC based on whether patients received primary surgical treatment. Therefore, we conducted a survival analysis based on different treatment modalities.

Methods:
This retrospective cohort study enrolled 125 patients with clinical stage T4b OSCC who received treatment and were followed up at Changhua Christian Hospital between January 1, 2008 and December 31, 2018.

Results:
Overall, 81 patients received primary surgical treatment and 44 received primary nonsurgical treatment. Comparison of the clinicopathological characteristics between those who did and did not undergo surgery revealed no significant differences in age at tumor diagnosis, tumor location, clinical N stage, and involved tumor area based on computed tomography or magnetic resonance imaging, or stratified Charlson Comorbidity Index scores. In the survival analysis, Kaplan–Meier curves revealed that patients who received treatment modalities including surgery exhibited better survival than those who received treatment modalities that did not include surgery.

Conclusions:
In the present study, patients with T4b OSCC treated with primary surgery had a better overall survival rate than those who received nonsurgical treatment. In the future, it will be necessary for clinicians worldwide to report the treatment outcomes of patients with T4b OSCC based on the common criteria.
Management strategy for extracranial carotid artery aneurysms
Authors: Choi Eol , Gwon Jun Gyo , Kwon Sun U. , Lee Deok Hee , Kwon Tae-Won , Cho Yong-Pil 
Published: May 2022

Abstract
This single-center, retrospective study aimed to describe the anatomic and clinical characteristics of extracranial carotid artery aneurysms (ECAAs) and to compare various ECAA management strategies in terms of outcomes.
A total of 41 consecutive patients, who underwent treatment for ECAAs between November 1996 and May 2020, were included in this study. The ECAAs were anatomically categorized using the Attigah and Peking Union Medical College Hospital (PUMCH) classifications. The possible study outcomes were restenosis or occlusion of the ipsilateral carotid artery after treatment and treatment-associated morbidity or mortality.
The 41 patients were stratified into three groups according to the management strategies employed: surgical (n = 25, 61.0%), endovascular (n = 10, 24.4%), and conservative treatment (n = 6, 14.6%). A palpable, pulsatile mass was the most common clinical manifestation (n = 16, 39.0%), and degenerative aneurysms (n = 29, 65.9%) represented the most common pathogenetic or etiological mechanism. According to the Attigah classification, type I ECAAs (n = 24, 58.5%) were the most common. Using the PUMCH classification, type I ECAAs (n = 26, 63.4%) were the most common. There was a higher prevalence of Attigah type I ECAAs among patients who underwent surgical treatment compared with those who underwent endovascular treatment (64.0% vs 40.0%, P = .09), whereas patients with PUMCH type IIa aneurysms were more likely to receive endovascular treatment (12.0% vs 30.0%). False aneurysms were more likely to be treated using endovascular techniques (20% vs 70%, P = 0.02). Except for two early internal carotid artery occlusions (one each among patients who underwent surgical and endovascular treatments, respectively), there were no early or late restenoses or occlusions during follow-up. Cranial nerve injuries were noted in three patients after surgical treatment, and late ipsilateral strokes occurred in two patients (one each among patients who underwent endovascular and conservative treatment, respectively). There were no other treatment-associated complications or deaths during the study period.

Conclusions:
Both surgical and endovascular treatments could be performed safely for ECAAs with good long-term results according to anatomic location and morphology.
Prevalence and Time Course of Thiamine Deficiency in Critically Ill Children: A Multicenter, Prospective Cohort Study in Turkey
Authors: Akkuzu Emine , Yavuz Sinan , Ozcan Serhan , Sincar Sahin , Bayrakci Benan , Kendirli Tanil , Pasaoglu Hatice , Kalkan Gokhan 
Published: May 2022

OBJECTIVES:
To determine the prevalence and time course of thiamine deficiency (TD) in PICU patients.

DESIGN:
Multicenter, prospective, cohort study between May 2019 and November 2019.

SETTING:
Three university-based tertiary care, mixed medical-surgical PICUs in Ankara, Turkey.

PATIENTS:
PICU patients 1 month to 18 years old.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
We studied 476 patients and grouped them by TD status on days 1 and 3 of the PICU admission. There might be a risk of unintended bias since we excluded 386 patients because of the absence of consent, inadequate blood samples, loss of identifier information, and recent vitamin supplementation. On day 1, TD was present in 53 of 476 patients (11.1%) and median (minimum–maximum) thiamine levels were 65.5 ng/mL (5–431 ng/mL). On day 3, TD was present in 27 of 199 patients (13.6%) with repeated measurement. The median (minimum–maximum) thiamine levels were 63 ng/mL (13–357 ng/mL). The time course of TD from day 1 to day 3 in these 199 patients was as follows. In 21 of 199 patients (10.6%) with TD on day 1, 11 of 21 (52%) continued to have TD on day 3 and the other 10 of 21 patients (48%) improved to no longer having TD. In 178 of 199 patients (89.4%) without TD on day 1, 16 of 178 (9%) went on to develop TD by day 3, and the other 162 of 178 (91%) continued to have normal thiamine status.

CONCLUSIONS:
In the PICU population in three centers in Turkey, the prevalence of TD in the sample of patients was 11.1%. In those TD patients who had serial studies, we also identified that by day 3 some continued to be TD, and some patients improved to normal thiamine status. Of concern, however, is the population who develop TD over the course of PICU stay.
Current Concepts in Maxillary Reconstruction
Authors: Lee Z-Hye , Cripps Courtney , Rodriguez Eduardo D. 
Published: May 2022

Summary:
Defects involving the midface and maxilla pose unique challenges to reconstructive surgeons. The maxilla serves as the central keystone of the face and interfaces with various other facial subunits to affect form and function. Reconstructive methods range from prosthetics to free tissue transfer, and the indications for different options are reviewed here. Finally, special considerations including management of the orbit, dental rehabilitation, and future directions are discussed.
Solitary Sphenoid Sinus Lesion Presenting as Chronic Headache
Authors: Kim Seo Bin , Kim Jooyeon , Kwon Jae Hwan 
Published: May 2022

Background and Objectives:
Headache is a common symptom with etiologies that are difficult to distinguish, 1 of which is sinusitis. A solitary sphenoid lesion, which is rare, can also cause acute or chronic headaches. The authors investigated whether endoscopic sinus surgery (ESS) for solitary sphenoid lesions could reduce headache symptoms.

Subjects and Methods:
The authors reviewed the charts of patients who underwent ESS from 2012 to 2017, whose main symptom was a chronic headache for several years. There were no remarkable pathologic findings in the nasal cavity upon endoscopic examination. Medications for reducing headaches had transient effect. Brain magnetic resonance imaging or computed tomography scans showed a solitary sphenoid lesion and the patients underwent ESS by the same otolaryngologist. In total, 16 out of 547 ESS cases that met the above conditions were included in this study. The authors evaluated the duration, character, and degree of the headaches pre- and post-operatively. The authors also determined if there was a correlation between headaches, sphenoidal lesions, and pathologic outcomes.

Results:
There were significant improvements in headaches after surgery. The pre- and post-operative mean visual analog scale score for headaches was 7.27 ± 1.67 and 3.80 ± 1.82, respectively. The pathologic outcomes revealed chronic inflammation in 11 patients, nasal polyp in 1 patient, inverted papilloma in 1 patient, and fungal infections in 3 patients, but there was no clinical correlation between the headache, lesion site, and pathology.

Conclusions:
A solitary sphenoid lesion can be the cause of acute or chronic headaches. Headaches from a solitary sphenoid sinus lesion, which were not controlled by medical treatments, could be improved by surgical procedures.
Endovascular Perfusion Augmentation for Critical Care Decreases Vasopressor Requirements while Maintaining Renal Perfusion
Authors: Patel Nathan T.P. , Gaffley Michaela , Leblanc Mathias J.R. , Lane Magan R. , Kratky Lauren E. , Hoareau Guillaume L. , Johnson M. Austin , Jordan James E. , Neff Lucas P. , Williams Timothy K. 
Published: May 2022

ABSTRACT

Background:
Ischemia reperfusion injury causes a profound hyperdynamic distributive shock. Endovascular perfusion augmentation for critical care (EPACC) has emerged as a hemodynamic adjunct to vasopressors and crystalloid. The objective of this study was to examine varying levels of mechanical support for the treatment of ischemiareperfusion injury in swine.

Methods:
Fifteen swine underwent anesthesia and then a controlled 30% blood volume hemorrhage followed by 30 min of supra-celiac aortic occlusion to create an ischemia-reperfusion injury Animals were randomized to standardized critical care (SCC), EPACC with low threshold (EPACC-Low), and EPACC with high threshold (EPACC-High). The intervention phase lasted 270 min after injury Hemodynamic markers and laboratory values of ischemia were recorded.

Results:
During the intervention phase, SCC spent 82.4% of the time avoiding proximal hypotension (>60 mm Hg), while EPACC-Low spent 97.6% and EPACC-High spent 99.5% of the time avoiding proximal hypotension, P
< 0.001. Renal artery flow was statistically increased in EPACC-Low compared with SCC (2.29 mL/min/kg vs. 1.77 mL/ min/kg, P
< 0.001), while renal flow for EPACC-High was statistically decreased compared with SCC (1.25 mL/min/kg vs. 1.77 mL/min/kg, P
< 0.001). EPACC animals required less intravenous norepinephrine, (EPACC-Low: 16.23mcg/kg and EPACC-High: 13.72 mcg/kg), compared with SCC (59.45 mcg/kg), P = 0.049 and P = 0.013 respectively.

Conclusions:
Compared with SCC, EPACC-High and EPACC-Low had decreased norepinephrine requirements with decreased frequency of proximal hypotension. EPACC-Low paradoxically had increased renal perfusion despite having a mechanical resistor in the aorta proximal to the renal arteries. This is the first description of low volume mechanical hemodynamic support in the setting of profound shock from ischemia-reperfusion injury in swine demonstrating stabilized proximal hemodynamics and augmented distal perfusion.
Contribution of IL-38 in Lung Immunity during Pseudomonas Aeruginosa-induced Pneumonia
Authors: Wei Qiang , Chen Xi , Chen Xia , Yuan Zhongzhen , Wang Chuanjiang 
Published: May 2022

ABSTRACT

Objective:
Interleukin-38 (IL-38), a new type of cytokine, is involved in processes such as tissue repair, inflammatory response, and immune response. However, its function in pneumonia caused by Pseudomonas aeruginosa (P. aeruginosa) is still unclear.

Methods:
In this study, we detected circulating IL-38 and cytokines such as IL-1β, IL-6, IL-17A, TNF-α, IL-8, and IL-10 in adults affected by early stage pneumonia caused by P. aeruginosa. Collected clinical data of these patients, such as the APACHE II score, levels of PCT, and oxygenation index when they entering the ICU. Using P. aeruginosa-induced pneumonia WT murine model to evaluate the effect of IL-38 on Treg differentiation, cell apoptosis, survival, tissue damage, inflammation, and bacterial removal.

Results:
In clinical research, although IL-38 is significantly increased during the early stages of clinical P. aeruginosa pneumonia, the concentration of IL-38 in the serum of patients who died with P. aeruginosa pneumonia was relatively lower than that of surviving patients. It reveals IL-38 may insufficiently secreted in patients who died with P. aeruginosa pneumonia. Besides, the serum IL-38 level of patients with P. aeruginosa pneumonia on the day of admission to the ICU showed significantly positive correlations with IL-10 and the PaO2/FiO2 ratio but negative correlations with IL-1β, IL-6, IL-8, IL-17, TNF-α, APACHE II score, and PCT In summary, IL-38 might be a molecule for adjuvant therapy in P. aeruginosa pneumonia. In experimental animal models, first recombinant IL-38 improved survival, whereas anti-IL-38 antibody reduced survival in the experimental pneumonia murine model. Secondly, IL-38 exposure reduced the inflammatory response, as suggested by the lung injury, and reduced cytokine levels (IL-1β, IL-6, IL- 17A, TNF-α, and IL-8, but not IL-10). It also increased bacterial clearance and reduced cell apoptosis in the lungs. Furthermore, IL-38 was shown to reduce TBK1 expression in vitro when naive CD4+ T lymphocytes were differentiated to Tregs and played a protective role in P. aeruginosa pneumonia.

Conclusions:
To summarize, the above findings provide additional insights into the mechanism of IL-38 in the treatment of P. aeruginosa pneumonia.
Impact of Underlying Disease and Preoperative Factors on Postoperative Outcomes After Laparoscopic Splenectomy: A Bicentric Retrospective Analysis
Authors: Peltrini Roberto , Di Nuzzo Maria M. , De Capua Michele , Andreuccetti Jacopo , D’Alessio Rossella , Baldoni Daniele , Bracale Umberto , Pignata Giusto , Corcione Francesco 
Published: May 2022

Background:
Although the laparoscopic approach is considered the gold standard for elective splenectomy, it is still debated whether the underlying disease affects postoperative outcomes. Given the importance of good patient selection in the early stages of the learning curve for laparoscopic splenectomy (LS), this study aimed to compare the postoperative outcomes following LS for malignant diseases and benign diseases (MDs and BDs).

Materials and Methods:
A retrospective review of patients who underwent LS was performed at 2 different institutions between January 2013 and September 2020. Patients were classified into 2 groups based on the underlying BDs or MDs, and the 30 days postoperative outcomes were compared. Risk factors for overall complications were determined using logistic regression analysis.

Results:
LS was performed for BDs and MDs in 51 (67%) and 25 (33%) patients, respectively. The overall morbidity rate and the intraoperative and postoperative complication rates were significantly higher in the MD group (P<0.05). In the univariate analysis, the underlying MD, age above 49.5 years, body mass index >24.9, the long axis of the spleen >16 cm, and spleen weight >600 g were significantly associated with increased postoperative morbidity.

Conclusion:
In addition to the underlying disease, preoperative conditions may also affect the complication rates after LS. These findings may be helpful in patient selection, especially in the early stages of the learning curve for minimally invasive splenectomies.
Delivering siRNA Compounds During HOPE to Modulate Organ Function: A Proof-of-concept Study in a Rat Liver Transplant Model
Authors: Bonaccorsi-Riani Eliano , Gillooly Andrew R. , Iesari Samuele , Brüggenwirth Isabel M.A. , Ferguson Chantal M. , Komuta Mina , Xhema Daela , Daumerie Aurélie , Maistriaux Louis , Leuvenink Henri , Kupiec-Weglinski Jerzy , Porte Robert J. , Khvorova Anastasia , Cave David R , Gianello Pierre , Martins Paulo N. 
Published: May 2022

Background.
Apoptosis contributes to the severity of ischemia-reperfusion injury (IRI), limiting the use of extended criteria donors in liver transplantation (LT). Machine perfusion has been proposed as a platform to administer specific therapies to improve graft function. Alternatively, the inhibition of genes associated with apoptosis during machine perfusion could alleviate IRI post-LT. The aim of the study was to investigate whether inhibition of an apoptosis-associated gene (FAS) using a small interfering RNA (siRNA) approach could alleviate IRI in a rat LT model.

Methods.
In 2 different experimental protocols, FASsiRNA (500 µg) was administered to rat donors 2 h before organ procurement, followed by 22 h of static cold storage, (SCS) or was added to the perfusate during 1 h of ex situ hypothermic oxygenated perfusion (HOPE) to livers previously preserved for 4 h in SCS.

Results.
Transaminase levels were significantly lower in the SCS-FASsiRNA group at 24 h post-LT. Proinflammatory cytokines (interleukin-2, C-X-C motif chemokine 10, tumor necrosis factor alpha, and interferon gamma) were significantly decreased in the SCS-FASsiRNA group, whereas the interleukin-10 anti-inflammatory cytokine was significantly increased in the HOPE-FASsiRNA group. Liver absorption of FASsiRNA after HOPE session was demonstrated by confocal microscopy; however, no statistically significant differences on the apoptotic index, necrosis levels, and FAS protein transcription between treated and untreated groups were observed.

Conclusions.
FAS inhibition through siRNA therapy decreases the severity of IRI after LT in a SCS protocol; however the association of siRNA therapy with a HOPE perfusion model is very challenging. Future studies using better designed siRNA compounds and appropriate doses are required to prove the siRNA therapy effectiveness during liver HOPE liver perfusion.
MICNet: Prediction of antibiotic susceptibility from microscopic images using transfer learning
Authors: Viehweger Adrian , Hölzer Martin , Brandt Christian 
Published: May 2022

AbstractRapid susceptibility testing of bacterial isolates is crucial for anti-infective therapy, especially in critical cases such as bacteriaemia and sepsis. Nevertheless, empiric therapy is often initiated immediately and without testing because two days and more pass between a positive blood culture and a susceptibility profile, so in the meantime, the most likely pathogens are treated. However, current empiric recommendations are very generic. They often remain unmodified even in light of incoming, early data specific to a patient’s case, such as positive blood culture microscopy. Part of the hesitancy to change treatments presumably stems from a lack of systematic integration of early information beyond expert intuition. To enable targeted antimicrobial therapy earlier in a case’s progression, we developed a method to predict antimicrobial susceptibility from microscopy images of bacteria alone. Our proof-of-concept MICNet combines two neural nets in a new chimerical architecture. It is pre-trained on about 100 thousand antibiograms and fine-tuned with only five thousand microscopic images through transfer learning. Predicting susceptibility profiles of four representative species, we show high predictive performance with a mean F-score of nearly 85%. In addition, several qualitative assessments show that our chimerical net has learned substantial expert knowledge. Therefore, MICNet is the first step towards personalized empiric therapy, combining prior pathogen probabilities with patient-specific data.