bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing therapeutic anti-cancer responses by combining immune checkpoint and tyrosine kinase inhibition
Authors: Daly Roger J. , Scott Andrew M. , Klein Oliver , Ernst Matthias 
Published: September 2022

AbstractOver the past decade, immune checkpoint inhibitor (ICI) therapy has been established as the standard of care for many types of cancer, but the strategies employed have continued to evolve. Recently, much clinical focus has been on combining targeted therapies with ICI for the purpose of manipulating the immune setpoint. The latter concept describes the equilibrium between factors that promote and those that suppress anti-cancer immunity. Besides tumor mutational load and other cancer cell-intrinsic determinants, the immune setpoint is also governed by the cells of the tumor microenvironment and how they are coerced by cancer cells to support the survival and growth of the tumor. These regulatory mechanisms provide therapeutic opportunities to intervene and reduce immune suppression via application of small molecule inhibitors and antibody-based therapies against (receptor) tyrosine kinases and thereby improve the response to ICIs. This article reviews how tyrosine kinase signaling in the tumor microenvironment can promote immune suppression and highlights how therapeutic strategies directed against specific tyrosine kinases can be used to lower the immune setpoint and elicit more effective anti-tumor immunity.
Boosting cisplatin chemotherapy by nanomotor-enhanced tumor penetration and DNA adducts formation
Authors: Xu Lihua , Zhang Kaixiang , Ma Xing , Li Yingying , Jin Yajie , Liang Chenglin , Wang Yong , Duan Wendi , Zhang Hongling , Zhang Zhenzhong , Shi Jinjin , Liu Junjie , Wang Yunlong , Li Wentao 
Published: September 2022

AbstractDespite many nano-based strategies devoted to delivering cisplatin for tumor therapy, its clinical benefits are compromised by poor tissue penetration and limited DNA adducts formation of the drug. Herein, a cisplatin loading nanomotor based janus structured Ag-polymer is developed for cisplatin delivery of deeper tissue and increased DNA adducts formation. The nanomotor displayed a self‐propelled tumor penetration fueled by hydrogen peroxide (H2O2) in tumor tissues, which is catalytically decomposed into a large amount of oxygen bubbles by Ag nanoparticles (NPs). Notably, cisplatin could elevate the intracellular H2O2 level through cascade reactions, further promote the degradation of Ag NPs accompanied with the Ag+ release, which could downregulate intracellular Cl− through the formation of AgCl precipitate, thereby enhancing cisplatin dechlorination and Pt–DNA formation. Moreover, polymer can also inhibit the activity of ALKBH2 (a Fe2+-dependent DNA repair enzyme) by chelating intracellular Fe2+ to increase the proportion of irreparable Pt–DNA cross-links. It is found that deep tissue penetration, as well as the increased formation and maintenance of Pt–DNA adducts induced by the nanomotor afford 80% of tumor growth inhibition with negligible toxicity. This work provides an important perspective of resolving chemotherapeutic barriers for boosting cisplatin therapy.
Graphical Abstract
Value of different anastomoses in laparoscopic radical right hemicolectomy for right-sided colon cancer: retrospective study and literature review
Authors: Wang Xiaoming , Ni Hongyan , Jia Wangqiang , Wang Sen , Zhang Yangyang , Zhao Peng , Yuan Long 
Published: September 2022

Abstract
Background
This study aimed to analyze the safety of circular lateral anastomosis and cross-lateral anastomosis in laparoscopic radical resection of right-sided colon cancer.

Methods
From January 2018 to March 2021, 147 patients with right-sided colon cancer were admitted to the Department of General Surgery, Cancer Hospital, Zhengzhou University. The experimental group comprised patients with circular lateral anastomosis, whereas the control group comprised patients with cruciform lateral anastomosis. The general clinical data, intraoperative features, and postoperative results of the two groups were compared and analyzed.

Results
Both groups successfully underwent laparoscopic lateral ileocolic anastomosis, with significant differences in anastomotic leakage (χ2=4.520, P < 0.05). By contrast, body mass index (t = 1.568, P = 0.119), histological typing (χ2 = 2.067, P = 0.559), intraoperative bleeding (t = 0.418, P = 0.677), and intestinal obstruction (χ2 = 2.564, P = 0.109) were not significantly different between the groups (P > 0.05).

Conclusions
In laparoscopic-assisted radical hemicolectomy for right-sided colon cancer, the incidence of postoperative anastomotic leakage was lower with circular lateral anastomosis than with cross-lateral anastomosis, and circular lateral anastomosis was superior to cross-lateral anastomosis in terms of reducing the length of hospital stay and improving patients' postoperative quality of life.
Prognostic value of lymph node density on cancer staging system for gastric cancer without distal metastasis: a population-based analysis of SEER database
Authors: Liu Yuhua , Cui Hao , Xu Xinxin , Liang Wenquan 
Published: September 2022

Abstract
Background
Accurate tumor staging is the cornerstone of tumor treatment. Current tumor staging system for gastric cancer (GC) is based on regional positive lymph nodes while ignoring the total number of examined lymph nodes. We aim to assess the prognostic value of lymph node density (LND), the ratio of positive nodes to the total number examined nodes, in GC without distal metastasis.

Methods
Clinical information of patients with histologically confirmed GC and without distal metastasis was identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The X-Tile software was used to identify the ideal prognosis-related cutoff point for LND. The prognostic value of LND on cancer-specific survival (CSS) and overall survival (OS) was assessed in Cox regression models. Subgroup analysis stratified by LND was performed on current lymph node staging system to further explore the interaction between LND and current lymph node staging system.

Results
A total of 4281 participants were identified from the SEER database for the final analysis. The optimal prognosis-related cutoff values of LND were calculated as 0.1 and 0.4, and LND was divided into three levels: LND1 (< 0.1), LND2 (> = 0.1, < 0.4), and LND3 (> = 0.4). LND3 was associated with worse CSS and OS in GC patients. Compared to patients with LND1, those with LND2 and LND3 had 2.43 (HR = 2.43, 95% CI 2.09–2.84, P < 0.001) and 4.69 (HR = 4.69, 95% CI 4.02–5.48, P < 0.001) folds increase in mortality in CSS, respectively. Similar results were found in the evaluation of OS in GC patients. Subgroup analysis stratified by LND also found that patients in the same current lymph node stage still had different prognosis due to the different LND levels after adjustment for other prognosis-related covariates (all P values < 0.001).

Conclusion
LND is an independent prognostic factor for GC without distal metastasis. In the current lymph node staging system, LND has potential value in further accurately classifying GC patients without distal metastasis.
A theory-based evaluation of the Leadership for Universal Health Coverage Programme: insights for multisectoral leadership development in global health
Authors: Witter Sophie , Brikci Nouria , Scherer David 
Published: September 2022

Abstract
Background
Leadership to manage the complex political and technical challenges of moving towards universal health coverage (UHC) is widely recognized as critical, but there are few studies which evaluate how to expand capacities in this area. This article aims to fill some of this gap by presenting the methods and findings of an evaluation of the Leadership for UHC (L4UHC) programme in 2019–2020.

Methods
Given the complexity of the intervention and environment, we adopted a theory-driven evaluation approach that allowed us to understand the role of the programme, amongst other factors. Data from a range of sources and tools were compared with a programme theory of change, with analysis structured using an evaluation matrix organized according to the Organisation for Economic Co-operation and Development–Development Assistance Committee (OECD-DAC) criteria. Data sources included key informant (KI) interviews (89 in total); surveys of the 80 workshop participants; a range of secondary data sources; case studies in two countries; and observation of activities and modules by the evaluator.

Results
Participants and KIs at the global and country levels reported high relevance of the programme and a lack of alternatives aiming at similar goals. In relation to effectiveness, at the individual level, there was an increase in some competencies, particularly for those with less experience at the baseline. Less change was observed in commitment to UHC as that started at a relatively high level. Understanding of UHC complexity grew, particularly for those coming from a non-health background. Connections across institutional divides for team members in-country increased, although variably across the countries, but the programme has not as yet had a major impact on national coalitions for UHC. Impacts on health policy and practice outcomes were evident in two out of seven countries. We examined factors favouring success and explanatory factors. We identified positive but no negative unintended effects.

Conclusions
While noting methodological constraints, the theory-based evaluation approach is found suitable for assessing and learning lessons from complex global programmes. We conclude that L4UHC is an important addition to the global and national health ecosystem, addressing a relevant need with some strong results, and also highlight challenges which can inform other programmes with similar objectives.
Operative public values as a tool for healthcare decisions: the social value and clinical criteria of triage
Authors: Cordeiro-Rodrigues Luis 
Published: September 2022

AbstractWith the current pandemic, many scholars have contended that clinical criteria offer the best way to implement triage. Further, they dismiss the criteria of social value as a good one for triage. In this paper, I respond to refute this perspective. In particular, I present two sets of arguments. Firstly, I argue that the objections to the social value criteria they present apply to the clinical criteria they favor. Secondly, they exaggerate the negative aspects of the social value criteria, while I suggest it is reasonable to use this. I end the article by recommending how operative public values can be a good way to make triaging decisions.
Linac-based stereotactic radiosurgery for brain arteriovenous malformations
Authors: Gawish Ahmed , Röllich Burkard , Ochel Hans-Joachim , Brunner Thomas B. 
Published: September 2022

Abstract
Purpose
Linac stereotactic radiosurgery (SRS) is gaining popularity as a form of radiation treatment for cerebral arteriovenous malformations (AVMs) since the theory of combined radiosurgical and endovascular treatment poses much uncertainty and due to significant technical progress for SRS. This study focuses on how to evaluate obliteration and re-bleeding rates, and to determine factors and adverse effects influencing obliteration after linac-based SRS for cerebral AVMs.

Material and methods
From a statistical record of 71 patients, 31 had partial embolisation, five surgery and 29 had no prior treatment. Using Kaplan–Meier survival and life table analyses, actuarial obliteration and annual bleeding hazard rates were calculated after SRS.

Results
After a follow up of 1, 2 and 3 years the actual obliteration rates were 22, 59 and 66%, respectively whereby it was noted that prior embolization had no effect on the obliteration rate. Annual bleeding hazard rates were further analyzed after stereotactic radiosurgery to be 2.1% and 1.4% for the first and second year respectively. Asymptomatic abnormalities were detected after imaging in 33.9% of patients. A dose of less than 18 Gy significantly reduced the obliteration probability.

Conclusion
SRS is a therapeutic option for intracerebral AVM. In general, there is a low rate of morbidity and a high probability of nidus obliteration.
Analgesic efficacy of adding the IPACK block to multimodal analgesia protocol for primary total knee arthroplasty: a meta-analysis of randomized controlled trials
Authors: Tang Xiumei , Lai Yahao , Du Siwei , Ning Ning 
Published: September 2022

Abstract
Background
Total knee arthroplasty (TKA) is a standard treatment for end-stage degenerative knee disease. Most patients will experience moderate-to-severe postoperative knee pain, significantly affecting rehabilitation. However, controversy remains regarding the efficacy of adding the interspace between the popliteal artery and capsule of the knee (IPACK) into multimodal analgesia protocol.

Methods
PubMed, Medline, Embase, Cochrane Library, and other databases were searched from inception to February 1, 2021. Studies comparing patients receiving IPACK to patients not receiving IPACK were included. The primary outcome was the ambulation pain score on a visual analogue scale (VAS) of 0–10. Secondary outcomes included pain score at rest, morphine usage, functional recovery, clinical outcomes, and complications.

Results
Thirteen RCTs involving 1347 knees were included. IPACK was associated with lower ambulation pain scores (weight mean difference [WMD] − 0.49, 95% confidence interval [CI] − 0.72 to − 0.26). The benefits were observed from 2 to 4 h, 6 to 12 h, and beyond one week. IPACK also significantly reduced rest pain scores (WMD − 0.49, 95% CI − 0.74 to − 0.24), and the benefits were observed from 6 to 12 h and beyond one week. IPACK reduced the overall morphine consumption (WMD − 2.56, 95% CI − 4.63 to − 0.49). Subgroup analysis found reduced oral morphine consumption from 24 to 48 h (WMD − 2.98, 95% CI − 5.71 to − 0.24) and reduced rate of morphine requirement from 12 to 24 h (relative risk [RR] = 0.51, 95% CI 0.31 to 0.83). Functional recovery outcomes regarding ambulation distances (on the second postoperative day [POD2]) (WMD = 1.74, 95% CI 0.34 to 3.15) and quadriceps muscle strength (at 0 degree) (WMD = 0.41, 95% CI 0.04 to 0.77) favored IPACK. And IPACK reduced the rate of sleep disturbance (on POD 1) (RR = 0.39, 95% CI 0.19 to 0.81). There was no significant difference in the other outcomes.

Conclusions
Moderate-level evidence confirmed that IPACK was related to better results in pain scores, morphine usage, and functional recovery without increasing the risk of complications.

Registration

CRD42021252156.
Needle-based gastrocnemius lengthening: a novel ultrasound-guided noninvasive technique
Authors: Iborra Marcos Álvaro , Villanueva Martínez Manuel , Fahandezh-Saddi Díaz Homid 
Published: September 2022

Abstract
Background
Gastrocnemius tendon lengthening is performed to treat numerous conditions of the foot and ankle. Gastrocnemius shortening has been associated with more than 30 lower limb disorders, including plantar heel pain/plantar fasciitis, Achilles tendinosis, equinus foot, adult flat foot deformity, and metatarsalgia. Ultrasound-guided ultraminimally invasive lengthening of the gastrocnemius is a step forward in this type of surgery. It can be performed in both legs simultaneously without ischemia using only local anesthesia plus sedation and without the need for a cast or immobilization. The truly novel advantage of the procedure is that it can be performed in the office, without specific surgical instruments. The aim of our research was to prove the effectiveness and safety of a new closed needle-based ultrasound-guided surgical procedure for lengthening the gastrocnemius tendon.

Methods and results
We performed ultrasound-guided gastrocnemius tendon lengthening using a needle in eight fresh frozen specimens (3 left and 5 right). None of the specimens had been affected by disease or undergone previous surgery that could have affected the surgical technique. We used a linear transducer with an 8- to 17-MHz linear transducer and the beveled tip of an Abbocath as a surgical blade to perform the lengthening procedure. The gastrocnemius Achilles tendon recession was entirely transected in all eight specimens, with no damage to the sural nerve or vessels. The improvement in dorsal flexion was 15°.

Conclusion
Needle-based ultrasound-guided gastrocnemius tendon lengthening is safe, since the surgeon can see all structures clearly, thus minimizing the risk of damage. The absence of a wound obviates the need for stitches, and recovery seems to be faster. The procedure can be performed in a specialist's office, as no specific surgical instruments are required. This technique could be a valid option for gastrocnemius lengthening and may even be less traumatic than using a hook-knife, as in our previous description.
Nitidine chloride induces caspase 3/GSDME-dependent pyroptosis by inhibting PI3K/Akt pathway in lung cancer
Authors: Yu Fei , Tan Weidan , Chen Zhiquan , Shen Xiaoju , Mo Xiaoxiang , Mo Xiaocheng , He Jingchuan , Deng Zhihua , Wang Jie , Luo Zhuo , Yang Jie 
Published: September 2022

Abstract
Background
As the increasing mortality and incidence of lung cancer (LC), there is an urgent need to discover novel treatment agent. In this study, we aimed to investigate the anti-LC effects of nitidine chloride (NC), a small molecular compound extracted from Chinese herbal medicine, while detailing its underlying mechanisms.

Methods
Cell viability was detected by MTT assays and five cell death inhibitors, including ferrostatin-1 (Fer-1), Z-VAD-FMK, necrostatin-1 (Nec-1), disulfiram (DSF) and IM-54 were used to explore the type of cell death induced by NC. The microscopic features of NC-induced pyroptosis were assessed by transmission electron microscopy (TEM) and the pyroptotic-related proteins such as caspase and gasdermin family, were examined by western blot. Network pharmacology was employed to predict the potential mechanisms of NC in lung cancer treatment. CETSA and DARTs were used to determine the activity of NC binding to targeted protein. Xenograft mice model was established to further investigate the inhibitory effect and mechanism of NC against LC.

Results
The pyroptosis inhibitor (DSF) and apoptosis inhibitor (Z-VAD-FMK) but not IM-54, necrostatin-1, or Ferrostatin-1 rescued NC-induced cell death. Morphologically, H1688 and A549 cells treated with NC showed notably pyroptotic features, such as cell swelling and large bubbles emerging from the plasma membrane. Gasdermin E (GSDME) rather than GSDMC or GSDMD was cleaved in NC-treated H1688 and A549 cells with an increased cleavage of caspase 3. Combined with network pharmacology and molecule docking, PI3K/Akt signaling axis was predicted and was further verified by CETSA and DARTs assay. In addition, the activation of PI3K is able to rescue the pyroptosis induced by NC in vitro. In xenograft model of LC, NC significantly hindered the transduction of PI3K-AKT pathway, inducing pyroptosis of tumor.

Conclusion
Our data indicated that NC is a potential therapeutic agent for the treatment of LC via triggering GSDME-dependent pyroptosis.
Clinical characteristics, healthcare use, and annual costs among patients with dystrophic epidermolysis bullosa
Authors: Feinstein James A. , Bruckner Anna L. , Chastek Benjamin , Anderson Amy , Roman Juan 
Published: September 2022

Abstract
Background
Dystrophic epidermolysis bullosa (DEB) is a serious, ultra-rare, genetic blistering disease that requires a multidisciplinary care team and lifelong, proactive disease management. To organize and optimize care, we comprehensively examined diagnoses, healthcare use, and annual costs in patients with DEB across all healthcare settings.

Methods
A retrospective study was performed using electronic health record (EHR) data from Optum Clinical Database (January 1, 2016, through June 30, 2020). Patients with an epidermolysis bullosa (EB) diagnosis between July 1, 2016, and December 31, 2019, with ≥ 6 months of baseline and 12 months of follow-up activity were included. Patients were stratified by EB type: recessive DEB (RDEB), dominant DEB (DDEB), DEB (type unknown), and EB unspecified. Demographics, comorbid conditions, and healthcare resource utilization were identified from EHR data. Cost of bandages and total medical costs (US$) were identified from linked claims data.

Results
A total of 412 patients were included, classified as having DDEB (n = 17), RDEB (n = 85), DEB (type unknown; n = 45), and EB unspecified (n = 265). Mean age was 38.4 years, and 41.7% had commercial insurance coverage. The most common comorbidities were mental health disorders, malnutrition, and constipation. Rates of cutaneous squamous cell carcinoma ranged from 0% (DDEB) to 4.4% (RDEB). Prescriptions included antibiotics (56.6%), pain medications (48.3%), and itch medications (50.7%). On average, patients had 19.7 ambulatory visits during the 12-month follow-up, 22.8% had an emergency department visit, and 23.8% had an inpatient stay. Direct medical costs among patients with claims data (n = 92) ranged from $22,179 for EB unspecified to $48,419 for DEB (type unknown).

Conclusions
This study demonstrated the range of comorbidities, multiple healthcare visits and prescription medications, and treatment costs during 1 year of follow-up for patients with DEB. The results underscore that the clinical and economic burden of DEB is substantial and primarily driven by supportive and palliative strategies to manage sequelae of this disease, highlighting the unmet need for treatments that instead directly address the underlying pathology of this disease.
Low dose of morphine to relieve dyspnea in acute respiratory failure (OpiDys): protocol for a double-blind randomized controlled study
Authors: Demoule Alexandre , Deleris Robin , Bureau Côme , Lebbah Said , Decavèle Maxens , Dres Martin , Similowski Thomas , Dechartres Agnes 
Published: September 2022

Abstract
Background
Dyspnea is common and severe in intensive care unit (ICU) patients managed for acute respiratory failure. Dyspnea appears to be associated with impaired prognosis and neuropsychological sequels. Pain and dyspnea share many similarities and previous studies have shown the benefit of morphine on dyspnea in patients with end-stage onco-hematological disease and severe heart or respiratory disease. In these populations, morphine administration was safe. Here, we hypothesize that low-dose opioids may help to reduce dyspnea in patients admitted to the ICU for acute respiratory failure. The primary objective of the trial is to determine whether the administration of low-dose titrated opioids, compared to placebo, in patients admitted to the ICU for acute respiratory failure with severe dyspnea decreases the mean 24-h intensity of dyspnea score.

Methods
In this single-center double-blind randomized controlled trial with 2 parallel arms, we plan to include 22 patients (aged 18–75 years) on spontaneous ventilation with either non-invasive ventilation, high flow oxygen therapy or standard oxygen therapy admitted to the ICU for acute respiratory failure with severe dyspnea. They will be assigned after randomization with a 1:1 allocation ratio to receive in experimental arm administration of low-dose titrated morphine hydrochloride for 24 h consisting in an intravenous titration relayed subcutaneously according to a predefined protocol, or a placebo (0.9% NaCl) administered according to the same protocol in the control arm. The primary endpoint is the mean 24-h dyspnea score assessed by a visual analog scale of dyspnea.

Discussion
To our knowledge, this study is the first to evaluate the benefit of opioids on dyspnea in ICU patients admitted for acute respiratory failure.

Trial registration
ClinicalTrials.govNCT04358133. Registered on 24 April 2020.