bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive value of proteomic markers for advanced rectal cancer with neoadjuvant chemoradiotherapy
Authors: Wang Hanyang , Ji Dengbo , Tian Huifang , Gao Zhaoya , Song Can , Jia Jinying , Cui Xinxin , Zhong Lijun , Shen Jing , Gu Jin 
Published: August 2022

Abstract
Background
Preoperative neoadjuvant chemoradiation (nCRT) has been the standard treatment for locally advanced rectal cancer. Serum biomarkers to stratify patients with respect to prognosis and response to nCRT are needed due to the diverse response to the therapy.

Methods
Thirteen paired pre- and post-nCRT sera from rectal cancer patients were analyzed by isobaric tags for relative and absolute quantitation (iTRAQ) method. Twenty-five proteins were selected for validation by parallel reaction monitoring (PRM) in ninety-one patients.

Results
Totally, 310 proteins were identified and quantified in sera samples. Reactome pathway analysis showed that the immune activation-related pathways were enriched in response to nCRT. Twenty-five proteins were selected for further validation. PRM result showed that the level of PZP was higher in pathological complete response (pCR) patients than non-pCR patients. The Random Forest algorithm identified a prediction model composed of 10 protein markers, which allowed discrimination between pCR patients and non-pCR patients (area under the curve (AUC) = 0.886 on testing set). Higher HEP2 and GELS or lower S10A8 in baseline sera were associated with better prognosis. Higher APOA1 in post nCRT sera was associated with better disease-free survival (DFS).

Conclusions
We identified and confirmed a 10-protein panel for nCRT response prediction and four potential biomarkers HEP2, GELS, S10A8 and APOA1 for prognosis of rectal cancer based on iTRAQ-based comparative proteomics screening and PRM-based targeted proteomic validation.
Correlation between national surveillance and search engine query data on respiratory syncytial virus infections in Japan
Authors: Uda Kazuhiro , Hagiya Hideharu , Yorifuji Takashi , Koyama Toshihiro , Tsuge Mitsuru , Yashiro Masato , Tsukahara Hirokazu 
Published: August 2022

Abstract
Background
The respiratory syncytial virus (RSV) disease burden is significant, especially in infants and children with an underlying disease. Prophylaxis with palivizumab is recommended for these high-risk groups. Early recognition of a RSV epidemic is important for timely administration of palivizumab. We herein aimed to assess the correlation between national surveillance and Google Trends data pertaining to RSV infections in Japan.

Methods
The present, retrospective survey was performed between January 1, 2018 and November 14, 2021 and evaluated the correlation between national surveillance data and Google Trends data. Joinpoint regression was used to identify the points at which changes in trends occurred.

Results
A strong correlation was observed every study year (2018 [r = 0.87, p < 0.01], 2019 [r = 0.83, p < 0.01], 2020 [r = 0.83, p < 0.01], and 2021 [r = 0.96, p < 0.01]). The change-points in the Google Trends data indicating the start of the RSV epidemic were observed earlier than by sentinel surveillance in 2018 and 2021 and simultaneously with sentinel surveillance in 2019. No epidemic surge was observed in either the Google Trends or the surveillance data from 2020.

Conclusions
Our data suggested that Google Trends has the potential to enable the early identification of RSV epidemics. In countries without a national surveillance system, Google Trends may serve as an alternative early warning system.
From motorised to active travel: using GPS data to explore potential physical activity gains among adolescents
Authors: Loh Venurs , Sahlqvist Shannon , Veitch Jenny , Thornton Lukar , Salmon Jo , Cerin Ester , Schipperijn Jasper , Timperio Anna 
Published: August 2022

Abstract
Background
A high proportion of adolescents worldwide are not doing enough physical activity for health benefits. Replacing short motorised trips with walking or cycling has the potential to increase physical activity at the population level. This study aimed to estimate the proportion of short distance motorised trips that could be replaced with walking or cycling, and the potential physical activity gains by sociodemographic and trip characteristics.

Methods
Data were from a subsample of the NEighbourhood Activity in Youth (NEArbY) study conducted among adolescents in Melbourne. A total of 217 adolescents with at least one motorised trip completed a survey and wore a Global Positioning Systems (GPS) device for eight consecutive days. Classification of travel modes were based on speed. GPS data points were geocoded in ArcGIS. Motorised trips within walkable (1.3 km) and cyclable (4.2 km) distances were identified (threshold based on 80th percentile of walking and cycling trip distances among Victorian adolescents), and the additional physical activity minutes that could be accrued by replacing walkable or cyclable motorised trip to active trips were quantified. Multilevel linear regression was used to assess differences in physical activity minutes gain by sociodemographic and trip characteristics.

Results
A total of 4,116 motorised trips were made. Of these, 17% were walkable and 61% were cyclable. Replacing motorised trips by walking and cycling resulted in estimated gains of six minutes and 15 min of physical activity per day, respectively.

Conclusion
The sizable proportion of replaceable trips and potential physical activity gains from this shift calls for attention to improve safe and connected infrastructure to support active travel.
Concurrence of IgG4-related disease and Kimura disease with pulmonary embolism and lung cancer: a case report
Authors: Lu Ye , Liu Junxiu , Yan Hengyi , Feng Wei , Zhao Li , Chen Yu 
Published: August 2022

AbstractBackgroundImmunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a systemic disease that involves the infiltration of IgG4-positive plasma cells in multiple organs. Kimura disease (KD) presents as subcutaneous masses on the head and neck, frequently accompanied by eosinophilia and high immunoglobulin E (IgE) levels. Here, we report a rare case of concurrence of IgG4-RD and KD with manifestations of asthma, pulmonary embolism, and central diabetes insipidus accompanied by lung carcinoma.Case presentationA 65-year-old Chinese male with an eight-year history of KD was admitted to our hospital with complaints of dyspnea and expectoration for one month. Laboratory examination showed a considerable elevation in the serum eosinophil count and total IgE and IgG4 levels. Chest enhanced computed tomography showed filling defects in the right pulmonary artery and a nodule in the left inferior lobe. Pancreatic enhanced magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography showed a swollen pancreatic tail and local stricture of the pancreatic duct section of the common bile duct. Enhanced MRI of the pituitary gland showed thickening of the pituitary stalk. Additionally, immunohistochemistry of the specimens collected eight years prior revealed IgG4-positive cells. Following the diagnosis of IgG4-RD with KD, glucocorticoids with immunosuppressants were initiated; there was a prompt improvement in the patient’s condition. One-year post-discharge, the patient underwent wedge-shaped resection of the lung due to enlargement of the pulmonary nodule, and the pathology revealed lung squamous carcinoma.ConclusionsThis case presents a rare clinical condition in which the concurrence of IgG4-RD and KD causes various rare manifestations including asthma, pulmonary embolism, central diabetes insipidus, and complicated lung carcinoma. This highlights the importance of monitoring for malignancies in IgG4-RD patients during follow-up.
KMT2C mutation in a Chinese man with primary multidrug-resistant metastatic adenocarcinoma of rete testis: a case report
Authors: Zhang Yue , He Xiaoyan , Gao Hui 
Published: August 2022

Abstract
Background
Adenocarcinoma of the rete testis (AORT) is an extremely rare malignant tumor with poor prognosis and limited responsiveness to traditional chemotherapy. Few previous studies have focused on the molecular mechanisms underlying therapy resistance in AORT and further scrutiny is required to enable searches for targeted drugs to guide treatment selection.

Case presentation
The current case concerns a 55-year-old man with AORT who presented with isolated bone metastasis at initial diagnosis and experienced rapid disease progression after multi-line platinum-based combination chemotherapy. Next-generation sequencing revealed a novel somatic lysine methyltransferase 2C (KMT2C) c.5605 T > C mutation in exon 36 with an abundance of 49.27%. The patient received antiangiogenic drug treatment for 2 months but this was discontinued due to unacceptable anorexia and nausea. He survived for 12 months after diagnosis.

Conclusion
A potential correlation between AORT primary multi-drug resistance and KMT2C mutations is implied. Further studies are needed to determine the efficacy of PARP1/2 inhibitors for tumors with KMT2C mutations.
Transition to practice curriculum for general internal medicine physicians: scoping review and Canadian national survey
Authors: Thomson Benjamin , O’Halloran Heather , Wu Luke , Gauthier Stephen , Taylor David 
Published: August 2022

Abstract
Background
There remains a paucity of evidence for curricula for the transition to practice (TTP) stage of Competence by Design internal medicine (IM) training programs. Current entrustable professional activities are based on expert consensus rather than robust subspecialty-specific needs assessment.

Methods
A scoping review was completed to identify studies with TTP focus. A national survey was conducted to identify transition experiences for general internal medicine physicians. Results were assessed by grounded theory analysis to identify core topics for TTP curricula.

Results
Neither scoping review nor national survey identified TTP topics related to the CanMEDS Medical Expert role. Scoping Review: 41 relevant studies were identified. Most (97.6%) were from North America. The most common study types were observational (survey) or curriculum (13/41 31.7% for each). Only two studies were exclusively in IM, and the most common subspecialty studied was surgical (13/41, 31.7%). The most common TTP topics were mentorship, billing and coding, practice management, negotiating contract and job, and financial aspects of practice. National Survey: There were 44 respondents, with the majority (25/44, 56.8%) having completed an IM subspecialty fellowship. Most (38/44) completed medical school in Canada, and most were from academic practice settings (33/44, 75.0%). The most common TTP topics were billing and coding, personal financial planning, practice management, work-life balance and mentorship. Grounded Theory Analysis: There were six themes that encompassed all TTP topics from the scoping review and national survey, being (i) building a career, (ii) continuing professional development, (iii) expectations of the profession, (iv) practice management, (v) Life, health and well-being and (vi) clinical skills. Curriculum competencies and resources for curriculum development were provided.

Conclusions
This study identifies topics critical for curricula development for IM transition to practice. Further research is required to evaluate effectiveness of curricula including topics and themes developed from this scoping review and national survey.
The test characteristics of a biased or ignorant diagnostician
Authors: Sonnenberg Amnon 
Published: August 2022

Abstract
Background
A human diagnostician may harbour a special bias towards favourable positive or negative test results. The aim of the present analysis is to describe in quantitative terms how bias can affect the test characteristics of a human tester.

Methods
Whereas an unbiased tester would give absolute (100%) preference to true positive or true negative test results, and no (0%) preference to any false positive or false negative test results, a biased tester may harbour some preferences towards false positive or false negative tests. Such bias can be phrased in terms of a separate sensitivity–specificity matrix. The bias matrix multiplied with the original test matrix yields the biased test matrix. Similarly, the extent of ignorance by a human tester about the diagnosis is modelled as a separate sensitivity–specificity matrix, which captures the concordance between positive and negative diagnoses made by an ignorant and expert diagnostician.

Results
Increasing bias or ignorance result in decreasing test performance with decreasing positive predictive values until the test completely loses its discriminatory power. With more pronounced bias towards false test results, any positive test outcome may even become misinterpreted as predicting the non-existence of a given diagnosis.

Conclusions
The proposed model helps to understand in quantitative terms, how bias and ignorance can alter a diagnostician’s interpretation of test outcomes and result in diagnostic errors.
A true congenital pancreatic cyst in a dog
Authors: Healy D. M. , Cassidy J. P. , Martin S. A. 
Published: August 2022

Abstract
Background
True congenital pancreatic cysts are a rare pathological process reported within feline and human literature. To date there has been no documented case of a true congenital cyst affecting a canine patient. The objective of this case report is to document the clinical findings, diagnostic investigations, surgical treatment, histopathological diagnosis and long-term outcome of a dog with a true pancreatic cyst.

Case presentation
A 5-month-old crossbreed dog was presented with a six-week history of abdominal pain, apparent bilateral pelvic limb weakness, reluctance to walk and intermittent vomiting and diarrhoea. An abdominal ultrasound examination performed by the dog’s primary care veterinarian identified a large intra-abdominal structure of unclear origin. A computed tomographic examination identified a large ovoid structure measuring 156 mm in length, 95 mm in height and 89 mm in width and apparently originating from the left limb of the pancreas. An exploratory coeliotomy was performed and a partial pancreatectomy was performed to allow complete removal of the cystic structure. Histopathological analysis of sections of the wall of the large fluid-filled cyst identified a thick fibromuscular wall lined by a well regimented hyperplastic tall columnar epithelium with basally located round to ovoid nuclei featuring fine chromatin stippling and abundant apically located and surface mucin, concurrent with a true congenital pancreatic cyst. A long-term follow-up of twenty-nine months identified no clinical signs of recurrence.

Conclusion
A partial pancreatectomy and en bloc excision of a true pancreatic cyst provided an excellent long-term outcome in a dog.
Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial
Authors: De Leeuw Elisabeth , Van Damme Karel F. A. , Declercq Jozefien , Bosteels Cedric , Maes Bastiaan , Tavernier Simon J. , Detalle Laurent , Smart Trevor , Glatt Sophie , Debeuf Nincy , Deckers Julie , Lameire Sahine , Vandecasteele Stefaan J. , De Neve Nikolaas , Demedts Ingel K. , Govaerts Elke , Knoop Christiane , Vanhove Karolien , Moutschen Michel , Terryn Wim , Depuydt Pieter , Van Braeckel Eva , Haerynck Filomeen , Hendrickx Tine C. J. , Parrein Vanessa , Lalla Marianna , Brittain Claire , Lambrecht Bart N. 
Published: August 2022

Abstract
Background
The efficacy and safety of complement inhibition in COVID-19 patients is unclear.

Methods
A multicenter randomized controlled, open-label trial. Hospitalized COVID-19 patients with signs of systemic inflammation and hypoxemia (PaO2/FiO2 below 350 mmHg) were randomized (2:1 ratio) to receive standard of care with or without the C5 inhibitor zilucoplan daily for 14 days, under antibiotic prophylaxis. The primary outcome was improvement in oxygenation at day 6 and 15.

Results
81 patients were randomly assigned to zilucoplan (n = 55) or the control group (n = 26). 78 patients were included in the safety and primary analysis. Most were men (87%) and the median age was 63 years. The mean improvement in PaO2/FiO2 from baseline to day 6 was 56.4 mmHg in the zilucoplan group and 20.6 mmHg in the control group (mean difference + 35.8; 95% confidence interval (CI) − 9.4 to 80.9; p = 0.12), an effect also observed at day 15. Day 28 mortality was 9% in the zilucoplan and 21% in the control group (odds ratio 0.4; 95% CI 0.1 to 1.5). At long-term follow up, the distance walked in a 6-min test was 539.7 m in zilucoplan and 490.6 m in the control group (p = 0.18). Zilucoplan lowered serum C5b-9 (p < 0.001) and interleukin-8 (p = 0.03) concentration compared with control. No relevant safety differences between the zilucoplan and control group were identified.

Conclusion
Administration of zilucoplan to COVID-19 patients in this proof-of-concept randomized trial was well tolerated under antibiotic prophylaxis. While not reaching statistical significance, indicators of respiratory function (PaO2/FiO2) and clinical outcome (mortality and 6-min walk test) suggest that C5 inhibition might be beneficial, although this requires further research in larger randomized studies.
Metabolic engineering of the l-serine biosynthetic pathway improves glutathione production in Saccharomyces cerevisiae
Authors: Kobayashi Jyumpei , Sasaki Daisuke , Hara Kiyotaka Y. , Hasunuma Tomohisa , Kondo Akihiko 
Published: August 2022

Abstract
Background
Glutathione is a valuable tri-peptide that is industrially produced by fermentation using the yeast Saccharomyces cerevisiae, and is widely used in the pharmaceutical, food, and cosmetic industries. It has been reported that addition of l-serine (l-Ser) is effective at increasing the intracellular glutathione content because l-Ser is the common precursor of l-cysteine (l-Cys) and glycine (Gly) which are substrates for glutathione biosynthesis. Therefore, we tried to enhance the l-Ser biosynthetic pathway in S. cerevisiae for improved glutathione production.

Results
The volumetric glutathione production of recombinant strains individually overexpressing SER2, SER1, SER3, and SER33 involved in l-Ser biosynthesis at 48 h cultivation was increased 1.3, 1.4, 1.9, and 1.9-fold, respectively, compared with that of the host GCI strain, which overexpresses genes involved in glutathione biosynthesis. We further examined simultaneous overexpression of SHM2 and/or CYS4 genes involved in Gly and l-Cys biosynthesis, respectively, using recombinant GCI strain overexpressing SER3 and SER33 as hosts. As a result, GCI overexpressing SER3, SHM2, and CYS4 showed the highest volumetric glutathione production (64.0 ± 4.9 mg/L) at 48 h cultivation, and this value is about 2.5-fold higher than that of the control strain.

Conclusions
This study first revealed that engineering of l-Ser and Gly biosynthetic pathway are useful strategies for fermentative glutathione production by S. cerevisiase.
Exercise and colorectal cancer: prevention and molecular mechanisms
Authors: Amirsasan Ramin , Akbarzadeh Maryam , Akbarzadeh Shabnam 
Published: August 2022

AbstractExercise and physical activity have been shown to be strongly associated with a decreased incidence rate of various chronic diseases especially numerous human malignancies. A huge number of clinical trials and meta-analysis have demonstrated that exercise is significantly effective in lowering the risk of colorectal cancer. In addition, it is suggested as an effective therapeutic modality against this cancer type. Therefore, in this review, we will review comprehensibly the effects of exercise in preventing, treating, and alleviating the adverse effects of conventional therapeutic options in colorectal cancer. Moreover, the possible mechanisms underlying the positive effects of exercise and physical activity in colorectal cancer, including regulation of inflammation, apoptosis, growth factor axis, immunity, epigenetic, etc. will be also discussed.
Short-term and long-term outcomes of indocyanine green for sentinel lymph node biopsy in early-stage breast cancer
Authors: Hua Bin , Li Yao , Yang Xin , Ren Xiaotian , Lu Xu 
Published: August 2022

Abstract
Background
Indocyanine green (ICG) is becoming a frequently used sentinel lymph node (SLN) tracer of breast cancer in China. However, there is still a lack of data on its safety. We reported the clinical outcome of ICG as a tracer of SLN over a median 67-month follow-up period to evaluate its feasibility in clinically node-negative patients with breast cancer.

Methods
A total of 194 consecutive patients underwent sentinel lymph node biopsy (SLNB) with ICG, radioisotopes (RI) and methylene blue (MB), or with ICG and MB. The SLN mapping data by each tracer was recorded, and safety outcomes were analyzed through follow-up.

Results
With the triad mapping (N = 44), the identification rate of SLN by ICG was 95.5%, slightly higher than that of MB (86.4%) and comparable with RI (95.5%) and combined methods (95.5%, 100%) (p = 0.068). Analysis of all candidates (N = 194) demonstrated that the identification rate of SLN by ICG or by ICG and MB was 99%, significantly higher than that by MB (92.8%) (p < 0.0001). No tracer-related allergic reaction and permanent skin staining of ICG were observed. Local disease progression was reported in 2 of the 194 patients at the ipsilateral axilla. After remedial axillary lymph node dissection, no disease progression was detected at follow-up.

Conclusions
ICG as an SLN tracer is more accurate than MB and comparable to the combined methods and has good clinical safety. ICG can be considered a useful supplement or suitable alternative to traditional tracers.