bluuebunny/crossref_metadata_2025_split huggingface dataset:
Social Determinants of Health Associated With the Development of Sepsis in Adults: A Scoping Review
Authors: Sheikh Fatima , Douglas William , Catenacci Vanessa , Machon Christina , Fox-Robichaud Alison E. 
Published: July 2022

OBJECTIVE:
Evaluating risk for sepsis is complicated due to limited understanding of how social determinants of health (SDoH) influence the occurence of the disease. This scoping review aims to identify gaps and summarize the existing literature on SDoH and the development of sepsis in adults.

DATA SOURCES:
A literature search using key terms related to sepsis and SDoH was conducted using Medline and PubMed.

STUDY SELECTION:
Studies were screened by title and abstract and then full text in duplicate. Articles were eligible for inclusion if they: 1) evaluated at least one SDoH on the development of sepsis, 2) participants were 18 years or older, and 3) the studies were written in English between January 1970 and January 2022. Systematic reviews, meta-analyses, editorials, letters, commentaries, and studies with nonhuman participants were excluded.

DATA EXTRACTION:
Data were extracted in duplicate using a standardized data extraction form. Studies were grouped into five categories according to the SDoH they evaluated (race, socioeconomic status [SES], old age and frailty, health behaviors, and social support). The study characteristics, key outcomes related to incidence of sepsis, mortality, and summary statements were included in tables.

DATA SYNTHESIS:
The search identified 637 abstracts, 20 of which were included after full-text screening. Studies evaluating SES, old age, frailty, and gender demonstrated an association between sepsis incidence and the SDoH. Studies that examined race demonstrated conflicting conclusions as to whether Black or White patients were at increased risk of sepsis. Overall, a major limitation of this analysis was the methodological heterogeneity between studies.

CONCLUSIONS:
There is evidence to suggest that SDoH impacts sepsis incidence, particularly SES, gender, old age, and frailty. Future prospective cohort studies that use standardized methods to collect SDoH data, particularly race-based data, are needed to inform public health efforts to reduce the incidence of sepsis and help clinicians identify the populations most at risk.
Mind the target: circulating tumour DNA in gastrointestinal malignancies
Authors: Fontana Elisa , Ignatova Ekaterina 
Published: July 2022

Purpose of review
Circulating tumour DNA (ctDNA) is an appealing minimally invasive tool with significant theranostic potential. In this review, we highlighted recent studies evaluating three major applications of ctDNA in gastrointestinal malignancies.

Recent findings
ctDNA demonstrated a strong prognostic value in colorectal and gastroesophageal cancers in assessing minimal residual disease after radical surgery. ctDNA-guided interventional studies are ongoing.
Tracking clonal dynamics with early identification of response and resistance to therapies is of particular interest in gastrointestinal cancers especially for established targeted therapies such as antiepidermal growth factor receptor (EGFR), BRAF inhibitors and immune checkpoint inhibitors.
Early cancer detection via ctDNA approaches is encouraging and of particular relevance in gastrointestinal cancers in view of limited screening programmes and yet poor outcomes of metastatic patients.

Summary
Although feasible and powerful tool, the clinical utility of ctDNA to guide patients’ management is challenging to demonstrate and requires further investigations in large interventional clinical trials.
Updated concepts in treatment of giant cell tumor of bone
Authors: van der Heijden Lizz , Lipplaa Astrid , van Langevelde Kirsten , Bovée Judith V.M.G. , van de Sande Michiel A.J. , Gelderblom Hans 
Published: July 2022

Purpose of review
Giant cell tumors of bone (GCTB) are intermediate, locally aggressive primary bone tumors. For conventional GCTB, surgery remains treatment of choice. For advanced GCTB, a more important role came into play for systemic therapy including denosumab and bisphosphonates over the last decade.

Recent findings
In diagnostics, focus has been on H3F3A (G34) driver mutations present in GCTB. The most frequent mutation (G34W) can be detected using immunohistochemistry and is highly specific in differentiating GCTB from other giant cell containing tumors. PD-L1 expression can be used as biological marker to predict higher recurrence risks in GCTB patients.
The use of bisphosphonate-loaded bone cement is under investigation in a randomized controlled trial. A new technique consisting of percutaneous microwave ablation and bisphosphonate-loaded polymethylmethacrylate cementoplasty was proposed for unresectable (pelvic) GCTB.
Increased experience with use of denosumab raised concern on elevated recurrence rates. However, conclusions of meta-analyses should be interpreted with risk of indication bias in mind. Several small studies are published with short-course denosumab (varying from 3 to 6 doses). One small trial directly compared denosumab and zoledronic acid, with no statistical differences in radiological and clinical outcome, and nonsignificantly higher recurrence rate after denosumab. As bisphosphonates directly target neoplastic stromal cells in GCTB, larger directly comparative trials are still warranted.

Summary
Neoadjuvant denosumab is highly effective for advanced GCTB, and a short-course is advised to facilitate surgery, whereas increased recurrence rates remain of concern. Randomized controlled trials are conducted on bisphosphonate-loaded bone cement and on optimal dose and duration of neoadjuvant denosumab. PD-L1 could be a potential new therapy target in GCTB.
Use of staging for sex cord stromal tumours
Authors: Negri Serena , Grassi Tommaso , Fruscio Robert 
Published: July 2022

Purpose of review
Sex cord-stromal tumours (SCSTs) are rare ovarian cancers. As in the literature, only small case series or case reports are published, gathering solid evidence about their management is challenging. Surgery plays a pivotal role, and accurate staging is one of the most important prognostic factors. This review focuses on the current evidence for surgical staging in the management of SCSTs.

Recent findings
Staging procedures have been inferred by epithelial ovarian cancers; however, they are often only partially performed, and most SCSTs therefore end up incompletely staged, raising the issue of the need for restaging or further treatments. In addition, some parts of the staging procedure have been questioned over the years, and lymphadenectomy is now considered unnecessary for SCSTs.
The generally favourable prognosis of SCSTs, the introduction of minimally invasive surgery and fertility-sparing approaches is empowering the question of which staging procedures are beneficial for these patients. We reviewed the role of each staging procedure proposed by the guidelines in light of new scientific updates.

Summary
Surgical staging should always be performed. It includes peritoneal samplings (peritoneal washing, multiple peritoneal biopsies, omental biopsy and biopsy of any suspicious area), whereas lymphadenectomy could be omitted. Laparoscopy may be considered a feasible approach.
Surgical treatment for clinical early-stage expansile and infiltrative mucinous ovarian cancer: can staging surgeries safely be omitted?
Authors: Algera Marc D. , van Driel Willemien J. , van de Vijver Koen K. , Kruitwagen Roy F.P.M. , Lok Christianne A.R. 
Published: July 2022

Purpose of review
Mucinous ovarian cancers (MOCs) are categorized into infiltrative and expansile subtypes. These subtypes have different characteristics and prognoses. Patients with clinical early-stage disease of both subtypes currently undergo surgical staging (peritoneal washing, biopsies, omentectomy). Peritoneal and lymph node metastases of expansile MOC are rare, but whereas lymph node sampling (LNS) is omitted in these patients, peritoneal staging is not. Therefore, we collected all available MOC data to determine whether staging surgeries could safely be omitted in clinical early-stage expansile and infiltrative MOC.

Recent findings
Current literature confirms that peritoneal metastases are rare in expansile MOC: more than 90% of patients have early-stage disease. Only 3.4% of the patients with clinical early-stage expansile MOC had positive peritoneal washings at surgical staging. Patients with infiltrative MOC were diagnosed more frequently with advanced-stage disease (21–54%). Moreover, upstaging clinical early-stage infiltrative MOC based on positive cytology, peritoneum and omentum metastases occurred in 10.3% of the patients. Therefore, we recommend that patients with early-stage infiltrative MOC undergo peritoneal staging and LNS. However, in addition to omitting LNS, we can also safely recommend omitting peritoneal staging in patients with clinical early stage expansile MOC.

Summary
Peritoneal metastases are rare in clinical early-stage expansile MOC and peritoneal staging can therefore safely be omitted.
Radiation therapy on the axilla after neoadjuvant chemotherapy
Authors: Meattini Icro , Salvestrini Viola , Becherini Carlotta 
Published: July 2022

Purpose of review
The introduction of primary systemic therapy has established a new treatment paradigm for breast cancer patients. However, recommendations for regional node irradiation after neoadjuvant chemotherapy are not supported by level I evidence, yet.

Recent findings
In addition to strategies optimising systemic treatments and surgery, current discussions focus on tailoring radiation therapy for breast cancer. Especially in view of the increasingly pivotal role of neoadjuvant chemotherapy, gauging the extent of radiation therapy in the breast and nodal volumes.

Summary
The current review focuses on recent evidence regarding radiation therapy of the breast and axilla in patients receiving neoadjuvant chemotherapy for primary breast cancer based on a PubMed and EMBASE literature search for publication years 2020–2022.
Human papillomavirus, tobacco, and poor oral hygiene can act synergetically, modulate the expression of the nuclear factor kappa B signaling pathway for the development and progression of head and neck cancer in the Pakistani population
Authors: Sarwar Sumaira , Mulla Mushir , Mulla Munaz , Tanveer Rida , Sabir Maimoona , Sultan Aneesa , Malik Salman A. 
Published: July 2022

Background:
Head and neck cancers (HNCs) are a heterogeneous group of tumors that progress owing to varied enviromental and genetic risk factors. Viral infections are threatening and adept at altering the expression of cellular transcription factors such as nuclear factor kappa B (NF-κB) and deregulation of other cellular proteins like NF kappa B inhibitor alpha (IκBα). The present study was conducted to detect high-risk genotypes of human papillomavirus (HPV) and protein expression of NF-κB signaling pathway in HNC patients with HPV infection.

Methods:
For HPV detection, genomic DNA from 152 HNC tumors was extracted formalin-fixed paraffin-embedded tissue DNA kit. For genotyping, polymerase chain reaction (PCR) using a general primer, HPV type-specific primers and agarose gel electrophoresis were performed. Immunohistochemistry (IHC) was also performed on 4-μm thick tissue sections using HPV E6 monoclonal antibody. Protein expression analysis of NF-κB signaling pathway including p50, p65, and IκBα was performed using IHC.

Results:
PCR analysis showed that 24.3% (37/152) of HNC cases were HPV positive. Among HPV positive, 86.5% (32/37) were tobacco users, while among HPV negative, 66.9% (77/115) were tobacco users. A significant association of HPV positivity and tobacco user was observed by univariate analysis [P
< 0.01; odds ratio (OR): 0.310, 95% confidence interval (CI): 0.110 to 0.870]. More HPV positive patients were with poor oral hygiene (78.3%) when compared with patients with good oral hygiene (21.6%) [P < 0.03, OR: 2.440, 95% CI: 1.650 to 3.600]. The results of the logistic regression analysis showed that age, tobacco use and oral hygiene are significant predictors (P < 0.02). PCR and IHC staining results confirmed that HPV16 was predominant among HNC cases (64.8%) when compared with HPV18 (35.2%). Expression of NF-κB proteins (p50, p65, and IκBα inhibitor) were also observed in HPV and non-HPV infected HNC tissues. IHC expression of p50, and p65 showed nuclear staining, while IκBα inhibitor showed cytoplasmic staining. Protein expression in HPV cases was higher as compared to HPV naive cases (P < 0.05).

Conclusions:
From the study, it can be established that the use of tobacco, oral hygiene, and HPV infection may be synergistically involved in modulating the expression of NF-κB signaling pathway for the development and progression of HNC in the Pakistani population.
Do methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 polymorphisms modify changes in intelligence of school-age children in areas of endemic fluorosis?
Authors: Feng Zichen , An Ning , Yu Fangfang , Ma Jun , Li Na , Du Yuhui , Guo Meng , Xu Kaihong , Hou Xiangbo , Li Zhiyuan , Zhou Guoyu , Ba Yue 
Published: July 2022

Abstract

Background:
Excessive exposure to fluoride can reduce intelligence. Methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 (MTHFD1) polymorphisms have important roles in neurodevelopment. However, the association of MTHFD1 polymorphisms with children's intelligence changes in endemic fluorosis areas has been rarely explored.

Methods:
A cross-sectional study was conducted in four randomly selected primary schools in Tongxu County, Henan Province, from April to May in 2017. A total of 694 children aged 8 to 12 years were included in the study with the recruitment by the cluster sampling method. Urinary fluoride (UF) and urinary creatinine were separately determined using the fluoride ion-selective electrode and creatinine assay kit. Children were classified as the high fluoride group and control group according to the median of urinary creatinine-adjusted urinary fluoride (UFCr) level. Four loci of MTHFD1 were genotyped, and the Combined Raven's Test was used to evaluate children's intelligence quotient (IQ). Generalized linear model and multinomial logistic regression model were performed to analyze the associations between children's UFCr level, MTHFD1 polymorphisms, and intelligence. The general linear model was used to explore the effects of gene-environment and gene-gene interaction on intelligence.

Results:
In the high fluoride group, children's IQ scores decreased by 2.502 when the UFCr level increased by 1.0 mg/L (β = −2.502, 95% confidence interval [CI]:−4.411, −0.593), and the possibility for having “excellent” intelligence decreased by 46.3% (odds ratio = 0.537, 95% CI: 0.290, 0.994). Children with the GG genotype showed increased IQ scores than those with the AA genotype of rs11627387 locus in the high fluoride group (P
< 0.05). Interactions between fluoride exposure and MTHFD1 polymorphisms on intelligence were observed (Pinteraction < 0.05).

Conclusion:
Our findings suggest that excessive fluoride exposure may have adverse effects on children's intelligence, and changes in children's intelligence may be associated with the interaction between fluoride and MTHFD1 polymorphisms.
Tumor microenvironment in lung cancer-derived brain metastasis
Authors: Liu Wenwen , Powell Charles A , Wang Qi 
Published: July 2022

Abstract
Brain metastasis (BM) is the leading cause of mortality in lung cancer patients. The process of BM (from initial primary tumor development, migration and intravasation, dissemination and survival in the bloodstream, extravasation, to colonization and growth to metastases) is a complex process for which few tumor cells complete the entire process. Recent research on BM of lung cancer has recently stressed the essential role of tumor microenvironment (TME) in assisting tumor cells in the completion of each BM step. This review summarizes recent studies regarding the effects of TME on tumor cells in the entire process of BM derived from lung cancer. The identification of vulnerable targets in the TME and their prospects to provide novel therapeutic opportunities are also discussed.
A Systematic Review of Conversion to Resectability in Unresectable Metastatic Colorectal Cancer Chemotherapy Trials
Authors: Chrabaszcz Sarah , Rajeev Rahul , Witmer Hunter D.D. , Dhiman Ankit , Klooster Brittany , Gamblin T. Clark , Banerjee Anjishnu , Johnston Fabian M. , Turaga Kiran K. 
Published: July 2022

Objectives:
Metastasectomy in patients with metastatic colorectal cancer (mCRC) confers a significant survival benefit. We hypothesized that conversion to resectability (C2R) correlates with superior overall survival (OS) in patients with unresectable mCRC.

Methods:
A prospectively registered systematic review (PROSPERO CRD42015024104) of randomized clinical trials published after 2003 was conducted. Exposure of interest was C2R with a primary outcome of OS. Clinical trials were classified based on difference in C2R between study arms (<2%, 2% to 2.9%, ≥3%). Generalized estimating equations were used to measure associations while adjusting for multiple observations from the same trial.

Results:
Of 2902 studies reviewed, 30 satisfied selection criteria (n=13,618 patients). Median C2R was 7.3% (interquartile range [IQR]: 5% to 12.9%), with maximum C2R in the FOLFOX/FOLFIRI+cetuximab arm (28.6%). The median difference in C2R between 2 arms of the same study was 2.3% (IQR: 1.3% to 3.4%) with a maximum difference of 15.4% seen in FOLFOX/FOLFIRI+cetuximab versus FOLFOX/FOLFIRI. Median OS for the entire patient cohort was 20.7 months (IQR: 18.9 to 22.7 mo), with a between group difference of 1.3 months (IQR: −1.2 to 3.6 mo). The median survival difference between the 2 study arms with <2% C2R difference was 0.8 months versus 1.6 months with ≥3% C2R rates . Increasing C2R had an incremental dose-effect response on OS (P=0.021), and higher response rates correlated with C2R rates (P=0.003).

Conclusions:
C2R occurs infrequently and variably in clinical trials enrolling patients with unresectable mCRC. Prioritization of chemotherapeutic agents that enhance C2R might improve OS of patients.
Factors Associated With Participation Rate and Predictive of Improvement After Cardiac Rehabilitation in Patients With Heart Failure
Authors: Wu Li-Hua , Wang Chao-Hung , Liu Min-Hui , Hsu Chih-Chin , Yuan Pei-Hsun , Fu Tieh-Cheng 
Published: July 2022

Purpose:
Patients with heart failure (HF) are often limited in their ability to perform exercise. Cardiac rehabilitation (CR) improves aerobic capacity and quality of life (QOL) and is recommended for patients with clinically stable HF; however, it is underutilized. The aim of this study was to investigate the factors associated with participation and completion rates and predictive of improvement after phase II CR in patients with HF.

Methods:
Participation and completion rates were calculated for all patients with HF enrolled in a multidisciplinary management program from October 2008 to December 2018. Functional capacity and QOL were estimated. In patients undergoing CR, changes in peak oxygen uptake (V˙ o2peak) were measured.

Results:
Of 662 patients enrolled, 448 (68%) completed the cardiopulmonary exercise test (CPX). Phase II CR was recommended in 411 patients, of whom 291 (71%) participated in CR. Participation was significantly related to sex and the time interval in days between hospital discharge and the CPX. Overall, 171 patients completed 36 sessions of CR (with a completion rate of 59%). During CR, there were 18 (6%) adverse events. Cardiac rehabilitation was associated with improvement in V˙ o2peak from 1153 ± 393 to 1342 ± 470 mL/min (a 16% improvement; P < .001) and in QOL. The independent predictors of increase in V˙ o2peak included sex, age, diabetes mellitus, and entry V˙ o2peak.

Conclusions:
In patients with HF, factors associated with CR participation rate included sex and days between hospital discharge and the CPX. Participation in CR improved V˙ o2peak and QOL. The improvement was related to male sex, younger age, no diabetes mellitus, and higher entry V˙ o2peak.
Bacterial overgrowth and lactose intolerance: how to best assess
Authors: Ghafoor Adil , Karunaratne Tennekoon , Rao Satish S.C. 
Published: July 2022

Purpose of review
To provide an up-to-date review on the clinical assessment of two important gastrointestinal problems with overlapping symptomatology but diverse cause and testing methods. Small intestinal bacterial overgrowth (SIBO) is characterized by the presence of excess bacteria in the small intestine associated with bloating, distention, gas, and diarrhea. Lactose intolerance is caused by lactase enzyme deficiency in the small bowel mucosa leading to lactose malabsorption and symptoms of bloating, gas, and diarrhea.

Recent findings
SIBO is assessed by hydrogen/methane breath test using glucose as a substrate and/or small bowel aspirate and culture but these tests have shortcomings. Consequently, several new diagnostic techniques, including novel capsule technologies and other approaches are being evaluated. Lactose intolerance can be assessed by hydrogen/methane breath test using lactose as a substrate, or small bowel mucosal lactase assay, genetic testing and lactose tolerance test, although the efficacy and practicality of these diagnostic modalities are not equal.

Summary
In clinical practice, gas, bloating, distention, pain, and diarrhea are common gastrointestinal symptoms that often remain unexplained when routine gastrointestinal endoscopy, imaging, and stool tests are negative. These patients should be evaluated for SIBO and/or food intolerances including lactose intolerance.
Emerging phenotypes of pulmonary hypertension associated with COPD: a field guide
Authors: García Agustín Roberto , Piccari Lucilla 
Published: July 2022

Purpose of review
Pulmonary hypertension (PH) is a common complication of chronic obstructive lung disease (COPD), but clinical presentation is variable and not always ’proportional’ to the severity of the obstructive disease. This review aims to analyze heterogeneity in clinical features of PH-COPD, providing a guide for diagnosis and management according to phenotypes.

Recent findings
Recent works have focused on severe PH in COPD, providing insights into the characteristics of patients with predominantly vascular disease. The recently recognized ’pulmonary vascular phenotype’, characterized by severe PH and mild airflow obstruction with severe hypoxemia, has markedly worse prognosis and may be a candidate for large trials with pulmonary vasodilators. In severe PH, which might be best described by a pulmonary vascular resistance threshold, there may also be a need to distinguish patients with mild COPD (pulmonary vascular phenotype) from those with severe COPD ('Severe COPD-Severe PH’ phenotype).

Summary
Correct phenotyping is key to appropriate management of PH associated with COPD. The lack of evidence regarding the use of pulmonary vasodilators in PH-COPD may be due to the existence of previously unrecognized phenotypes with different responses to therapy. This review offers the clinician caring for patients with COPD and PH a phenotype-focused approach to diagnosis and management, aimed at personalized care.