bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between oligo-residual disease and patterns of failure during EGFR-TKI treatment in EGFR-mutated non-small cell lung cancer: a retrospective study
Authors: Miyawaki Taichi , Kenmotsu Hirotsugu , Kodama Hiroaki , Nishioka Naoya , Miyawaki Eriko , Mamesaya Nobuaki , Kobayashi Haruki , Omori Shota , Ko Ryo , Wakuda Kazushige , Ono Akira , Naito Tateaki , Murakami Haruyasu , Mori Keita , Harada Hideyuki , Endo Masahiro , Takahashi Kazuhisa , Takahashi Toshiaki 
Published: November 2021

Abstract
Background
Local ablative therapy (LAT) may be beneficial for patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) with oligo-residual disease after treatment with EGFR tyrosine kinase inhibitor (EGFR-TKI). However, this has not been fully established. This study aimed to evaluate the predominant progressive disease (PD) pattern limited to residual sites of disease after treatment with EGFR-TKI.

Methods
Patients with advanced EGFR-mutated NSCLC treated with EGFR-TKIs as first-line therapy were retrospectively analysed during a 7-year period. Oligo-residual disease was defined as the presence of 1 – 4 lesions (including the primary site) at 3 months from the start of EGFR-TKI treatment. The predictive factors of PD patterns after EGFR-TKI treatment were evaluated.

Results
A total of 207 patients were included. Three months after the start of EGFR-TKI treatment, 66 patients (32%) had oligo-residual disease. A total of 191 patients had PD, 60 with oligo-residual disease and 131 with non-oligo-residual disease. Regarding the pattern, 44 patients (73%) with oligo-residual disease and 37 patients (28%) with non-oligo-residual disease had PD limited to the residual sites. Multivariate logistic regression analysis at 3 months from the start of EGFR-TKI treatment revealed that oligo-residual disease (P < 0.001), the lack of residual central nervous system metastases (P = 0.032), and initial treatment with osimertinib (P = 0.028) were independent predictors of PD limited to residual disease sites.

Conclusions
This study provided a rationale for LAT to all sites of residual disease in patients with oligo-residual disease during EGFR-TKI treatment.
Stepwise correlation of TP53 mutations from pancreaticobiliary maljunction to gallbladder carcinoma: a retrospective study
Authors: Kawakami Satoshi , Takano Shinichi , Fukasawa Mitsuharu , Shindo Hiroko , Takahashi Ei , Fukasawa Yoshimitsu , Hayakawa Hiroshi , Kuratomi Natsuhiko , Kadokura Makoto , Hosomura Naohiro , Amemiya Hidetake , Kawaida Hiromichi , Kono Hiroshi , Maekawa Shinya , Ichikawa Daisuke , Enomoto Nobuyuki 
Published: November 2021

Abstract
Background
The genetic changes underlying carcinogenesis in patients with risk factors of gallbladder carcinoma (GBC) remains controversial, especially in patients with pancreaticobiliary maljunction (PBM). This study aimed to clarify the association between risk factors of GBC and genetic changes using next-generation sequencing (NGS).

Methods
We retrospectively analyzed resected tissues of 64 patients who were diagnosed with GBC (n = 26), PBM [with GBC (n = 8), without GBC (n = 20)], and chronic cholecystitis, used as a control group (n = 10). DNA was extracted from tumors and their surrounding tissues, which were precisely separated by laser-capture microdissection. Gene alterations of 50 cancer-related genes were detected by NGS and compared with clinical information, including PBM status.

Results
The most frequent gene alterations in GBC tissues occurred in TP53 (50%), followed by EGFR (20.6%), RB1 (17.6%), and ERBB2 (17.6%). Gene alterations that were targetable by molecular targeted drugs were detected in 20 cases (58.8%). Statistical analysis of gene alterations and risk factors revealed that TP53 alteration rate was higher in GBC patients with PBM than those without PBM (p = 0.038), and the TP53 mutation rates in the epithelium of control patients, epithelium of PBM patients without GBC, peritumoral mucosa of GBC patients with PBM, and tumor tissue of GBC patients with PBM were 10, 10, 38, and 75%, respectively (p <  0.01).

Conclusions
TP53 alteration more than KRAS mutation was revealed to underlie carcinogenesis in patients with PBM.
Methylphenidate augmentation of escitalopram to enhance adherence to antidepressant treatment: a pilot randomized controlled trial
Authors: Paulus Martin P. , Kuplicki Rayus , Victor Teresa A. , Yeh Hung-Wen , Khalsa Sahib S. 
Published: November 2021

Abstract
Background
Adherence to treatment, i.e. the extent to which a patient’s therapeutic engagement coincides with the prescribed treatment, is among the most important problems in mental health care. The current study investigated the influence of pairing an acute positive reinforcing dopaminergic/noradrenergic effect (methylphenidate, MPH) with a standard antidepressant on the rates of adherence to medication treatment. The primary objective of this study was to determine whether MPH + escitalopram resulted in higher rates of medication adherence relative to placebo + escitalopram.

Methods
Twenty participants with moderate to severe depression were 1–1 randomized to either (1) 5 mg MPH + 10 mg escitalopram or (2) placebo + 10 mg escitalopram with the possibility for a dose increase at 4 weeks. A Bayesian analysis was conducted to evaluate the outcomes.

Results
First, neither percent Pill count nor Medication Electronic Monitoring System adherence showed that MPH was superior to placebo. In fact, placebo showed slightly higher adherence rates on the primary (7.82% better than MPH) and secondary (7.07% better than MPH) outcomes. There was a less than 25% chance of MPH augmentation showing at least as good or better adherence than placebo. Second, both groups showed a significant effect of treatment on the QIDS-SR with a median effect of an 8.6-point score reduction. Third, neither subjective measures of adherence attitudes nor socio-demographic covariates had a significant influence on the primary or secondary outcome variables.

Conclusions
These data do not support the use of MPH to increase adherence to antidepressant medication in individuals with moderate to severe depression.

ClinicalTrials.gov identifier
NCT03388164, registered on 01/02/2018.
Farsi version of the CLEFT-Q: translation, cultural adaptation process and reliability
Authors: Ajami Shabnam , Torabi Shiva , Dehghanpour Samaneh , Ajami Maryam 
Published: November 2021

Abstract
Background
The purpose of this study was the translation and cultural adaptation of the CLEFT-Q to Farsi and evaluating the reliability of it.

Methods
The English version of the CLEFT-Q was translated to Farsi following the guidelines set forth by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). To calculate the reliability, 50 participants filled out the Farsi version of the questionnaire twice at 2-week intervals.

Results
The difficulties during the translation and cultural adaptation process were as follows: 7.56% of items from the independent forward translations, 62.18% of items from the comparison between two forward translations, and 21% of items from the comparison between post-back translation and the original version. The internal consistency and stability of the Farsi version of the CLEFT-Q were 0.979 and 0.997, which both were categorized as excellent.

Conclusion
The Farsi version of the CLEFT-Q is a valid and reliable tool currently available for Farsi-speaking families around the world.
Pathological investigations and correlation research of microfibrillar-associated protein 4 and tropoelastin in oral submucous fibrosis
Authors: Liu Binjie , Gou Wenqun , Feng Hui 
Published: November 2021

Abstract
Background
Oral submucous fibrosis (OSF), distinguished by abnormal collagen deposition, is a potentially malignant disorder with 4.2% (95% CI 2.7–5.6%) of malignant transformation and rising global prevalence. However, the precise pathogenesis and effective treatment remain elusive and controversial despite the abundance of literature on this topic. Therefore, it is crucial to explore the clinicopathological characteristics and potential markers for the diagnosis and prognosis of OSF. The objective of this study was to evaluate the influence and correlation of Microfibrillar-associated protein 4 (MFAP4) and tropoelastin (TE) in the development of OSF patients.

Material and methods
Clinicopathological factors, hematoxylin–eosin (HE) and Masson trichome staining, immunohistochemical characteristics and the correlation between MFAP4 and TE were recorded and compared among different stages of OSF progression among cases (n = 60) and controls (n = 10). Student's t test, ANOVA analysis, and the chi-square test were performed to compare the categorical variables for clinicopathological characteristics and the expression level of MFAP4 and TE between the fibrotic and normal tissues. Correlation analysis of MFAP4 and TE was performed using Pearson's correlation test and linear regression.

Results
MFAP4 and TE proteins are upregulated and increased gradually in patients with varying stages of OSF, relative to the control group. Furthermore, statistical analyses revealed that the expression level of MFAP4 was positively associated with TE, with a Pearson correlation coefficient of 0.3781 (p = 0.0048). Clinically, we found that OSF affected more males than females, with a ratio of 29:1. The age range was 16–60 years, and the mean age was 36.25 ± 10.25 years. In patients younger than 40 years, the positive expression rate of MFAP4 and TE was higher than in those over 40 years. All OSF cases had chewed areca nut, with 51.67% smoking tobacco.

Conclusions
Our study elucidates that the accumulation of MFAP4 and TE proteins may play a vital role in the occurrence and development of OSF and may be promising candidate moleculars for prevention, diagnosis, and treatment strategies for OSF in the future.
Hospitalisation events in people with chronic kidney disease as a component of multimorbidity: parallel cohort studies in research and routine care settings
Authors: Sullivan Michael K. , Jani Bhautesh Dinesh , McConnachie Alex , Hanlon Peter , McLoone Philip , Nicholl Barbara I. , Carrero Juan-Jesus , Nitsch Dorothea , McAllister David , Mair Frances S. , Mark Patrick B. 
Published: November 2021

Abstract
Background
Chronic kidney disease (CKD) typically co-exists with multimorbidity (presence of 2 or more long-term conditions: LTCs). The associations between CKD, multimorbidity and hospitalisation rates are not known. The aim of this study was to examine hospitalisation rates in people with multimorbidity with and without CKD. Amongst people with CKD, the aim was to identify risk factors for hospitalisation.

Methods
Two cohorts were studied in parallel: UK Biobank (a prospective research study: 2006-2020) and Secure Anonymised Information Linkage Databank (SAIL: a routine care database, Wales, UK: 2011-2018). Adults were included if their kidney function was measured at baseline. Nine categories of participants were used: zero LTCs; one, two, three and four or more LTCs excluding CKD; and one, two, three and four or more LTCs including CKD. Emergency hospitalisation events were obtained from linked hospital records.

Results
Amongst 469,339 UK Biobank participants, those without CKD had a median of 1 LTC and those with CKD had a median of 3 LTCs. Amongst 1,620,490 SAIL participants, those without CKD had a median of 1 LTC and those with CKD had a median of 5 LTCs. Compared to those with zero LTCs, participants with four or more LTCs (excluding CKD) had high event rates (rate ratios UK Biobank 4.95 (95% confidence interval 4.82–5.08)/SAIL 3.77 (3.71–3.82)) with higher rates if CKD was one of the LTCs (rate ratios UK Biobank 7.83 (7.42–8.25)/SAIL 9.92 (9.75–10.09)). Amongst people with CKD, risk factors for hospitalisation were advanced CKD, age over 60, multiple cardiometabolic LTCs, combined physical and mental LTCs and complex patterns of multimorbidity (LTCs in three or more body systems).

Conclusions
People with multimorbidity have high rates of hospitalisation. Importantly, the rates are two to three times higher when CKD is one of the multimorbid conditions. Further research is needed into the mechanism underpinning this to inform strategies to prevent hospitalisation in this very high-risk group.
Detection of toxoplasmosis in pets and stray cats through molecular and serological techniques in Khyber Pakhtunkhwa, Pakistan
Authors: Majid Abdul , Ahmad Nisar , Haleem Sumbal , Akbar Noor ul , Zareen Shehzad , Taib Muhammad , Khan Sanaullah , Hussain Rafiq , Sohail  
Published: November 2021

Abstract
Background
Toxoplasma gondii is an important parasite that belongs to the phylum Apicomplexa, distributed globally, causing major health issues for a wide range of hosts, including humans, native and wild animals.

Methods
In the present study, we detected IgG and IgM antibodies through an ELISA kit and DNA of T. gondii through PCR in 197 pets and stray cats in Peshawar, Charsadda, Mardan, and Kohat districts of Khyber Pakhtunkhwa (Pakistan) to estimate the existence of feline toxoplasmosis.

Results
The current study revealed that stray cats have a significant infection rate of T. gondii (74.6%) as compared to pet cats (25.4%). In all the four districts, the prevalence of T. gondii was pointedly higher in district Kohat (95.5%) in the feline population. In comparison to the female (75.18%) and male (both pets and stray) cats have a maximum infection of (81.66%) non-significantly. The prevalence of T. gondii was observed to be significantly higher (91.66%) in the older and greater than 4 year old population of cats as compared to the younger ones. In poor health condition, the cat populations has a higher risk of infection of 92.3% as compared to healthy and poor body condition (73.91%) and (82.6%) respectively. The chronic and reactivated chronic conditions of toxoplasmosis were higher (58.37%) as compared to the acute condition.

Conclusion
It has been concluded that toxoplasmosis is widely spread in the studied population.The outcomes of the present study show that T. gondii infection has a significant impact on the type of cat, age, and area, which implies a serious threat to human beings. Therefore, genotyping of T. gondii strains from different hosts is needed to forecast the current approach for prevention and control of this zoonotic parasite.
Atomically precise silver clusterzymes protect mice from radiation damages
Authors: Guo Jiao , Yang Haiyu , Liu Ya , Liu Wei , Zhao Ruiying , Li He , Long Wei , Xu Wenqing , Guo Meili , Zhang Xiaodong 
Published: November 2021

Abstract
Background
As we know, radiotherapy plays an irreplaceable role in the clinical management on solid tumors. However, due to the non-specific killing effects of ionizing radiation, normal tissues damages would be almost simultaneous inevitably. Therefore, ideal radioprotective agents with high efficiency and low toxicity are always desirable. In this work, atomically precise Ag14 clusterzymes were developed, and their applications in radioprotection were studied in vitro and in vivo for the first time.

Methods
The ultra-small glutathione supported Ag14 clusterzymes were synthesized by convenient sodium borohydride (NaBH4) reduction of thiolate-Ag (I) complexes and then they were purified by desalting columns. The enzyme-like activity and antioxidant capacity of Ag14 clusterzymes have been tested by various commercial kits, salicylic acid method and electron spin resonance (ESR). Next, they were incubated with L929 cells to evaluate whether they could increase cell viability after γ-ray irradiation. And then Ag14 clusterzymes were intravenously injected into C57 mice before 7 Gy whole-body γ-ray irradiation to evaluate the radioprotection effects in vivo. At last, the in vivo toxicities of Ag14 clusterzymes were evaluated through biodistribution test, hematological details, serum biochemical indexes and histological test in female Balb/c mice with intravenous injection of Ag14 clusterzymes.

Results
Our studies suggested atomically precise Ag14 clusterzymes were potential radioprotectants. Ag14 clusterzymes exhibited unique superoxide dismutase (SOD)-like activity, strong anti-oxidative abilities, especially on •OH scavenging. The Ag14 clusterzymes could effectively improve cell viability through eliminating ROS and prevent DNA damages in cells dealt with γ-ray irradiation. In vivo experiments showed that Ag14 clusterzymes could improve the irradiated mice survival rate by protecting hematological systems and repairing tissue oxidative stress damage generated by γ-ray irradiation. In addition, bio-distribution and toxicological experiments demonstrated that the ultrasmall Ag14 clusterzymes could be excreted quickly from the body by renal clearance and negligible toxicological responses were observed in mice up to 30 days.

Conclusion
In summary, atomically precise, ultrasmall and water soluble Ag14 clusterzymes with SOD-like activity were successfully developed and proved to be effective both in vitro and in vivo for radioprotection. Furthermore, with atomically precise molecular structure, Ag14 clusterzymes, on aspect of the catalytic and optical properties, may be improved by structure optimization on atom-scale level for other applications in disease diagnosis and treatment.

Graphical Abstract
RETRACTED ARTICLE: A stepwise-targeting strategy for the treatment of cerebral ischemic stroke
Authors: Hu Jingbo , Tan Xueying , Wang Dongwei , Li Yixuan , Liang Hongze , Peng Jiejun , Li Fengyan , Zhou Quan , Geng Peiwu , Wang Shuanghu , Yu Yue , Liu Jin 
Published: November 2021

Abstract
Background
Effective amelioration of neuronal damages in the case of cerebral ischemic stroke (CIS) is essential for the protection of brain tissues and their functional recovery. However, most drugs can not penetrate the blood–brain barrier (BBB), resulting in the poor therapeutic outcomes.

Results
In this study, the derivatization and dual targeted delivery technologies were used to actively transport antioxidant melatonin (MLT) into the mitochondria of oxidative stress-damaged cells in brain tissues. A mitochondrial targeting molecule triphenylphosphine (TPP) was conjugated to melatonin (TPP-MLT) to increase the distribution of melatonin in intracellular mitochondria with the push of mitochondrial transmembrane potential. Then, TPP-MLT was encapsulated in dual targeted micelles mediated by TGN peptide (TGNYKALHPHNG) with high affinity for BBB and SHp peptide (CLEVSRKNG) for the glutamate receptor of oxidative stress-damaged neural cells.TGN/SHp/TPP-MLT micelles could effectively scavenge the overproduced ROS to protect neuronal cells from oxidative stress injury during CIS occurrence, as reflected by the improved infarct volume and neurological deficit in CIS model animals.

Conclusions
These promising results showed this stepwise-targeting drug-loaded micelles potentially represent a significant advancement in the precise treatment of CIS.

Graphical Abstract
Implementation and first-year operating costs of an academic medical center-based syringe services program
Authors: Bartholomew Tyler S. , Patel Hardik , McCollister Kathryn , Feaster Daniel J. , Tookes Hansel E. 
Published: November 2021

Abstract
Background
Syringe services programs (SSPs) remain highly effective, cost-saving interventions for the prevention of blood-borne infections among people who inject drugs. However, there have been restrictions regarding financial resources allocated to these programs, particularly in the US South. This study aimed to provide cost data regarding the implementation and first-year operations of an academic-based SSP utilizing fixed and mobile strategies, including the integration of onsite wound care.

Methods
We conducted a micro-costing study that retrospectively collected detailed resource utilization and unit cost data for both the fixed and mobile SSP strategies, including onsite wound care, from both healthcare and societal perspectives. A three-step approach was used to identify, measure, and value intervention costs, and cost components were categorized into implementation, variable program, and time-dependent costs. Sensitivity analysis was performed to examine the impact of SSP operational changes (i.e., needs-based distribution and opt-out HIV/HCV testing) on the cost-per-participant. Cost data we presented as overall cost and cost-per-participant adjusted to 2017 US dollars.

Results
A total of 452 and 129 participants enrolled in fixed and mobile SSP services, respectively. The total cost associated with implementation and first year operations for the fixed site was $407,217.22 or $729.72 per participant and $311,625.52 or $2415.70 per participant for the mobile unit. The largest cost component for both modalities was time-dependent costs (personnel and overhead), while intervention materials (syringes, injection equipment, naloxone) were less than 15% of the total program cost.

Discussion/conclusion
Implementation and operation of new SSP models continue to be low cost compared to treatment for the multitude of harms PWID face without access to evidence-based prevention. Future cost-effectiveness and cost–benefit analyses integrating a comprehensive SSP model within an academic institution, including onsite wound care and other medical services, will provide a more comprehensive understanding of this model, and state-level policy action must be taken to lift the prohibition of state and local funds for the implementation, sustainability, and maintenance of these programs in Florida.