bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness analysis of initial nonoperative management versus emergency laparoscopic appendectomy for acute complicated appendicitis
Authors: Sugiura Kiyoaki , Suzuki Keiichi , Umeyama Tomoshige , Omagari Kenshi , Hashimoto Takeo , Tamura Akihiko
Published: November 2020

Background

The evidence regarding the safety and efficacy of nonoperative management is growing. However, the best treatment strategy for acute complicated appendicitis remains controversial. We aimed to evaluate the cost-effectiveness of treatment strategies for complicated appendicitis patients. This study sought to determine the most cost-effective strategy from the health care-payer’s perspective.

Methods

The primary outcome was an incremental cost effectiveness ratio (ICER) using nonoperative management with or without interval laparoscopic appendectomy (ILA) as the intervention compared with operative management with emergency laparoscopic appendectomy (ELA) alone as the control. Model variables were abstracted from a literature review, and from data obtained from the hospital records of Tochigi Medical Center. Cost-effectiveness was evaluated using an ICER. We constructed a Markov model to compare treatment strategies for complicated appendicitis in otherwise-healthy adults, over a time horizon of a single year. Uncertainty surrounding model parameters was assessed via one-way- and probabilistic-sensitivity analyses. Threshold analysis was performed using the willingness-to-pay threshold set at the World Health Organization’s criterion of $107,690.

Results

Three meta-analysis were included in our analysis. Operative management cost $6075 per patient. Nonoperative management with interval laparoscopic appendectomy (ILA) cost $984 more than operative management and produced only 0.005 more QALYs, resulting in an ICER of $182,587. Nonoperative management without ILA cost $235 more than operative management, and also yielded only 0.005 additional QALYs resulting in an ICER of $45,123 per QALY. Probabilistic sensitivity analysis with 1000 draws resulted in average ICER of $172,992 in nonoperative management with ILA and $462,843 in Nonoperative management without ILA. The threshold analysis demonstrated that regardless of willingness-to-pay, nonoperative management without ILA would not be most cost-effective strategy.

Conclusions

Nonoperative management with ILA and Nonoperative management without ILA were not cost-effective strategies compared with operative management to treat complicated appendicitis. Based on our findings, operative management remains the standard of care and nonoperative management would be reconsidered as a treatment option in complicated appendicitis from economic perspective.
Interprofessional collaboration associated with frequency of life-saving links to HIV continuum of care services in the urban environment of Newark, New Jersey
Authors: Windsor Liliane Cambraia , Pinto Rogério Meireles , Lee Carol Ann
Published: November 2020

Background

HIV continuum of care has been used as a strategy to reduce HIV transmission rates, with timely engagement in HIV testing being the first and most critical step. This study examines interprofessional-collaboration (IPC) after controlling for agency/ provider demographics, provider training and self-efficacy as a significant predictor of how frequently HIV service providers link their clients to HIV testing.

Methods

Multilevel binary logistic regression analysis was conducted to examine the effects of IPC on links to HIV testing while controlling for demographic and agency information, provider training, and standardized measures of providers’ feelings, attitudes, and opinions about IPC. Cross-sectional data from 142 providers in 13 agencies offering treatment and prevention services for HIV and substance-use disorders were collected via a survey.

Results

Those who scored higher on the IPC scale reported significantly higher rates of linkages to HIV testing. Compared to the null model (i.e., no predictor model), the final multilevel binary logistic regression model showed a significantly improved likelihood of linkage to HIV testing by 11.4%, p. < .05. The final model correctly classified 90.2% of links to HIV testing. Providers in agencies with smaller budgets and in agencies offering substance use disorder services were more likely to link clients to HIV testing. Younger providers who received HIV training were also more likely to link clients to HIV testing.

Conclusions

Findings suggest IPC training as a potential strategy to improve linkages to HIV testing for clients at risk for HIV infection. Future research is recommended to identify specific areas of IPC that might have differential effects on links to HIV testing.
Development of a multivariable prediction model to identify patients unlikely to complete a colonoscopy following an abnormal FIT test in community clinics
Authors: Petrik Amanda F. , Keast Erin , Johnson Eric S. , Smith David H. , Coronado Gloria D.
Published: November 2020

Background

Colorectal cancer (CRC) is the 3rd leading cancer killer among men and women in the US. The Strategies and Opportunities to STOP Colon Cancer in Priority Populations (STOP CRC) project aimed to increase CRC screening among patients in Federally Qualified Health Centers (FQHCs) through a mailed fecal immunochemical test (FIT) outreach program. However, rates of completion of the follow-up colonoscopy following an abnormal FIT remain low. We developed a multivariable prediction model using data available in the electronic health record to assess the probability of patients obtaining a colonoscopy following an abnormal FIT test.

Methods

To assess the probability of obtaining a colonoscopy, we used Cox regression to develop a risk prediction model among a retrospective cohort of patients with an abnormal FIT result.

Results

Of 1596 patients with an abnormal FIT result, 556 (34.8%) had a recorded colonoscopy within 6 months. The model shows an adequate separation of patients across risk levels for non-adherence to follow-up colonoscopy (bootstrap-corrected C-statistic > 0.63). The refined model included 8 variables: age, race, insurance, GINI income inequality, long-term anticoagulant use, receipt of a flu vaccine in the past year, frequency of missed clinic appointments, and clinic site. The probability of obtaining a follow-up colonoscopy within 6 months varied across quintiles; patients in the lowest quintile had an estimated 18% chance, whereas patients in the top quintile had a greater than 55% chance of obtaining a follow-up colonoscopy.

Conclusions

Knowing who is unlikely to follow-up on an abnormal FIT test could help identify patients who need an early intervention aimed at completing a follow-up colonoscopy.

Trial registration

This trial was registered at ClinicalTrials.gov (NCT01742065) on December 5, 2012. The protocol is available.
Solitary tracheal B-cell lymphoma in an adult alpaca (Vicugna pacos)
Authors: Marchionatti Emma , Van der Vekens Elke , Peters Laureen Michèle , Kaiponen Taina Susanna , Berenguer Veiga Inês , Zanolari Patrik
Published: November 2020

Background

This report describes a case of solitary tracheal lymphoma in a 14-year-old alpaca mare.

Case presentation

The alpaca was referred for dyspnea and inspiratory noise. The clinical examination included complete blood cell count, blood chemistry, endoscopy, ultrasound, radiographs, and computed tomography (CT). A solitary tracheal intraluminal and juxtatracheal lymphoma was diagnosed by fine needle aspiration (FNA). The owner requested euthanasia due to the uncertain prognosis. At postmortem examination, the presence of solitary lymphoma without involvement of other organs was confirmed. Immunohistochemical analysis confirmed a B-cell origin.

Conclusions

Although multicentric lymphoma is the most commonly described neoplasia affecting South American camelids (SAC), solitary forms of the disease may occur.
Tuberculosis caused by Mycobacterium caprae in a camel (Camelus dromedarius)
Authors: Infantes-Lorenzo J. A. , Romero B. , Rodríguez-Bertos A. , Roy A. , Ortega J. , de Juan L. , Moreno I. , Domínguez M. , Domínguez L. , Bezos J.
Published: November 2020

Background

Animal tuberculosis (TB) is distributed worldwide and has a wide range of wild and domestic reservoirs. Few studies concerning TB in camelids have been published in the last decade, particularly as regards Old World Camelids (OWC), but the increase in reports of TB outbreaks in these species in recent years suggests a high susceptibility to the infection.

Case presentation

We studied a dromedary camel (Camelus dromedarius) herd (n = 24) in which aMycobacterium capraeinfection was detected. The TB infection was confirmed in one animal at necropsy through the detection of TB lesions, mainly in the abdominal organs, and the subsequent isolation ofM. caprae(SB0157 spoligotype). The whole herd was additionally tested using cellular and humoral based diagnostic techniques. The intradermal tuberculin test results were compared with those obtained using P22 ELISA for the detection of specific antibodies against theM. tuberculosiscomplex. The TB infected animal was a positive reactor to both the intradermal tuberculin tests and P22 ELISA, while the others were negative to all the diagnostic tests.

Conclusion

The present study foundM. capraeinfection in OWC. This is the first report ofM. capraeinfection in an OWC not living in a zoo. Since the animal was born in the herd and fed with goat’s milk, this practice was suspected to be the potential source of TB infection, which was not confirmed in the other animals present in the herd. Moreover, our results highlight that the intradermal tuberculin test and the P22 ELISA could be valuable tools for the diagnosis of TB in OWC.
CD4 T-cell immune stimulation of HER2 + breast cancer cells alters response to trastuzumab in vitro
Authors: Song Patrick N. , Mansur Ameer , Dugger Kari J. , Davis Tessa R. , Howard Grant , Yankeelov Thomas E. , Sorace Anna G.
Published: November 2020

Introduction

The HER2 + tumor immune microenvironment is composed of macrophages, natural killer cells, and tumor infiltrating lymphocytes, which produce pro-inflammatory cytokines. Determining the effect of T-cells on HER2 + cancer cells during therapy could guide immunogenic therapies that trigger antibody-dependent cellular cytotoxicity. This study utilized longitudinal in vitro time-resolved microscopy to measure T-cell influence on trastuzumab in HER2 + breast cancer.

Methods

Fluorescently-labeled breast cancer cells (BT474, SKBR3, MDA-MB-453, and MDA-MB-231) were co-cultured with CD4 + T-cells (Jurkat cell line) and longitudinally imaged to quantify cancer cell viability when treated with or without trastuzumab (10, 25, 50 and 100 μg/mL). The presence and timing of T-cell co-culturing was manipulated to determine immune stimulation of trastuzumab-treated HER2 + breast cancer. HER2 and TNF-α expression were evaluated with western blot and ELISA, respectively. Significance was calculated using a two-tailed parametrict-test.

Results

The viability of HER2 + cancer cells significantly decreased when exposed to 25 μg/mL trastuzumab and T-cells, compared to cancer cells exposed to trastuzumab without T-cells (p = 0.01). The presence of T-cells significantly increased TNF-α expression in trastuzumab-treated cancer cells (p = 0.02). Conversely, cancer cells treated with TNF-α and trastuzumab had a similar decrease in viability as trastuzumab-treated cancer cells co-cultured with T-cells (p = 0.32).

Conclusions

The presence of T-cells significantly increases the efficacy of targeted therapies and suggests trastuzumab may trigger immune mediated cytotoxicity. Increased TNF-α receptor expression suggest cytokines may interact with trastuzumab to create a state of enhanced response to therapy in HER2 + breast cancer, which has potential to reducing tumor burden.
Kelch 13-propeller polymorphisms in Plasmodium falciparum from Jazan region, southwest Saudi Arabia
Authors: Dafalla Ommer Mohammed , Alzahrani Mohammed , Sahli Ahmed , Al Helal Mohammed Abdulla , Alhazmi Mohammad Mohammad , Noureldin Elsiddig Mohammed , Mohamed Waheed Sideeg , Hamid Tajeldin Bashir , Abdelhaleem Aymen Awad , Hobani Yahya Ali , Arif Ommar Ali , Bokar Ibrahim Munagi , Hakami Abdulazai Mohammed , Eisa Zaki Manawar
Published: November 2020

Background

Artemisinin-based combination therapy (ACT) is recommended at the initial phase for treatment ofPlasmodium falciparum, to reduce morbidity and mortality in all countries where malaria is endemic. Polymorphism in portions ofP. falciparumgene encoding kelch (K13)-propeller domains is associated with delayed parasite clearance after ACT. Of about 124 different non-synonymous mutations, 46 have been identified in Southeast Asia (SEA), 62 in sub-Saharan Africa (SSA) and 16 in both the regions. This is the first study designed to analyse the prevalence of polymorphism in theP. falciparum k13-propeller domain in the Jazan region of southwest Saudi Arabia, where malaria is endemic.

Methods

One-hundred and fortyP. falciparumsamples were collected from Jazan region of southwest Saudi Arabia at three different times: 20 samples in 2011, 40 samples in 2016 and 80 samples in 2020 after the implementation of ACT.Plasmodium falciparum kelch13(k13) gene DNA was extracted, amplified, sequenced, and analysed using a basic local alignment search tool (BLAST).

Results

This study obtained 51 non-synonymous (NS) mutations in three time groups, divided as follows: 6 single nucleotide polymorphisms (SNPs) ‘11.8%’ in samples collected in 2011 only, 3 (5.9%) in 2011and 2016, 5 (9.8%) in 2011 and 2020, 5 (9.8%) in 2016 only, 8 (15.7%) in 2016 and 2020, 14 (27.5%) in 2020 and 10 (19.6%) in all the groups. The BLAST revealed that the 2011 isolates were genetically closer to African isolates (53.3%) than Asian ones (46.7%). Interestingly, this proportion changed completely in 2020, to become closer to Asian isolates (81.6%) than to African ones (18.4%).

Conclusions

Despite the diversity of the identified mutations in thek13-propeller gene, these data did not report widespread artemisinin-resistant polymorphisms in the Jazan region where these samples were collected. Such a process would be expected to increase frequencies of mutations associated with the resistance of ACT.
Circular RNA hsa_circ_0004872 inhibits gastric cancer progression via the miR-224/Smad4/ADAR1 successive regulatory circuit
Authors: Ma Cunying , Wang Xiaoying , Yang Fenghua , Zang Yichen , Liu Jiansong , Wang Xinyi , Xu Xia , Li Wenjuan , Jia Jihui , Liu Zhifang
Published: November 2020

Background

Emerging evidence has shown that circular RNAs (circRNAs) play a crucial regulatory role in the occurrence and development of cancer. Exploring the roles and mechanisms of circRNAs in tumorigenesis and progression may help to identify new diagnostic markers and therapeutic targets. In the present study, we investigated the role and regulatory mechanism of hsa_circ_0004872 in gastric cancer (GC).

Methods

qRT-PCR was used to determine the expression of hsa_circ_0004872 in GC tissues and cells. EdU, CCK-8, transwell and scratch wound healing assays were used to assess the role of hsa_circ_0004872 in GC cell proliferation, invasion and migration, respectively. Subcutaneous and tail vein tumor injections in nude mice were used to assess the role of hsa_circ_0004872 in vivo. RIP assay, biotin-coupled probe pull-down assay, FISH and luciferase reporter assay were performed to confirm the relationship between hsa_circ_0004872 and the identified miRNA. ChIP assay, luciferase reporter assay and western blot were used to determine the direct binding of Smad4 to the promoter of the ADAR1 gene.

Results

In this study, we found that hsa_circ_0004872 was dramatically downregulated in GC tissues compared with adjacent noncancerous tissues. The expression level of hsa_circ_0004872 was associated with tumor size and local lymph node metastasis. Enforced expression of hsa_circ_0004872 inhibited the proliferation, invasion and migration of GC cells, whereas knockdown of hsa_circ_0004872 had the opposite effects. Nude mice experiments showed that ectopic expression of hsa_circ_0004872 dramatically inhibited tumor growth and metastasis in vivo. Moreover, we demonstrated that hsa_circ_0004872 acted as a “molecular sponge” for miR-224 to upregulate the expression of the miR-224 downstream targets p21 and Smad4. Importantly, we found that the RNA-editing enzyme ADAR1 inhibited hsa_circ_0004872 expression and further led to the upregulation of miR-224. Smad4, the downstream target of miR-224, could further affect hsa_circ_0004872 levels by directly binding to the promoter region of ADAR1 to inhibit ADAR1 expression.

Conclusions

Our findings showed that hsa_circ_0004872 acted as a tumor suppressor in GC by forming a negative regulatory loop consisting of hsa_circ_0004872/miR-224/Smad4/ADAR1. Thus, hsa_circ_0004872 may serve as a potential biomarker and therapeutic target for GC.
Elucidating the cellular response of silver nanoparticles as a potential combinatorial agent for cisplatin chemotherapy
Authors: Rank Miranda Renata , Pereira da Fonseca Micaella , Korzeniowska Barbara , Skytte Lilian , Lund Rasmussen Kaare , Kjeldsen Frank
Published: November 2020

Background

Combination chemotherapy uses drugs that target different cancer hallmarks, resulting in synergistic or additive toxicity. This strategy enhances therapeutic efficacy as well as minimizes drug resistance and side effects. In this study, we investigated whether silver nanoparticles act as a combinatorial partner to cisplatin. In so doing, we compared post-exposure biological endpoints, intracellular drug accumulation, and changes in the proteome profile of tumoral and normal cell lines.

Results

Combinatorial exposure corresponded to cytotoxicity and oxidative stress in both cell lines, yet was substantially more effective against tumoral cells. Proteome analysis revealed that proteins related to energy metabolism pathways were upregulated in both cell lines, suggesting that combinatorial exposure corresponded to energetic modulation. However, proteins and upstream regulators involved in the cell cycle were downregulated, indicating reduced cell proliferation. The response to oxidative stress was markedly different in both cell lines; downregulation of antioxidant proteins in tumoral cells, yet upregulation of the antioxidant defense system in normal cells. These outcomes may have avoided higher cell death rates in normal cells.

Conclusions

Taken together, our results indicate that combining silver nanoparticles with cisplatin increases the biological activity of the latter, and the combination warrants further exploration for future therapies.
Enhanced antitumor effects of follicle-stimulating hormone receptor-mediated hexokinase-2 depletion on ovarian cancer mediated by a shift in glucose metabolism
Authors: Zhang Meng , Liu Qiyu , Zhang Mingxing , Cao Cong , Liu Xiaoxia , Zhang Mengyu , Li Guiling , Xu Congjian , Zhang Xiaoyan
Published: November 2020

Background

Most cancers favor glycolytic-based glucose metabolism. Hexokinase-2 (HK2), the first glycolytic rate-limiting enzyme, shows limited expression in normal adult tissues but is overexpressed in many tumor tissues, including ovarian cancer. HK2 has been shown to be correlated with the progression and chemoresistance of ovarian cancer and could be a therapeutic target. However, the systemic toxicity of HK2 inhibitors has limited their clinical use. Since follicle-stimulating hormone (FSH) receptor (FSHR) is overexpressed in ovarian cancer but not in nonovarian healthy tissues, we designed FSHR-mediated nanocarriers for HK2 shRNA delivery to increase tumor specificity and decrease toxicity.

Results

HK2 shRNA was encapsulated in a polyethylene glycol-polyethylenimine copolymer modified with the FSH β 33–53 or retro-inverso FSH β 33–53 peptide. The nanoparticle complex with FSH peptides modification effectively depleted HK2 expression and facilitated a shift towards oxidative glucose metabolism, with evidence of increased oxygen consumption rates, decreased extracellular acidification rates, and decreased extracellular lactate and glucose consumption in A2780 ovarian cancer cells and cisplatin-resistant A2780CP counterpart cells. Consequently, cell proliferation, invasion and migration were significantly inhibited, and tumor growth was suppressed even in cisplatin-resistant ovarian cancer. No obvious systemic toxicity was observed in mice. Moreover, the nanoparticle complex modified with retro-inverso FSH peptides exhibited the strongest antitumor effects and effectively improved cisplatin sensitivity by regulating cisplatin transport proteins and increasing apoptosis through the mitochondrial pathway.

Conclusions

These results established HK2 as an effective therapeutic target even for cisplatin-resistant ovarian cancer and suggested a promising targeted therapeutic approach.
Content validation of the Kamath and Stothard questionnaire for carpal tunnel syndrome diagnosis: a cognitive interviewing study
Authors: Dabbagh Armaghan , MacDermid Joy C. , Packham Tara L. , Macedo Luciana G.
Published: November 2020

Background

Accurate diagnosis of carpal tunnel syndrome (CTS) is essential for directing appropriate treatment; and for making decisions about work injury claims. The Kamath and Stothard Questionnaire (KSQ) is a self-reported tool used for the diagnosis of CTS. Comprehensibility and comprehensiveness of this questionnaire are critical to diagnostic performance and need to be established. The purpose of the study was to describe how potential respondents, clinicians, and measurement researchers interpret KSQ questions in order to identify and resolve potential sources of misclassification.

Methods

Hand therapists, measurement researchers, participants with CTS, and a control group were interviewed using cognitive interviewing techniques (talk aloud, semi-structured interview probes) in Hamilton, Canada. All interviews were recorded and transcribed verbatim. A directed content analysis was done to analyze the interviews using a previously established framework.

Findings

Eighteen participants were interviewed. Areas, where questions were unclear to some participants, were recorded and categorized into five themes: Clarity and Comprehension (52%), Relativeness (38%), Inadequate Response Definition (4%), Perspective Modifiers (4%), and Reference Point (2%). Respondents also identified several symptoms of CTS that are not covered by the KSQ that might be of diagnostic value, e.g., weakness and dropping items.

Conclusion

The content validity of the current iteration of the KSQ was not established. The problematic questions identified in the study have been reported to have low specificity and negative predictive values in a previous quantitative study. The content validity issues identified may explain the poor performance. Recommendations were made to modify the wording of the KSQ and the potential addition of three new questions. Future studies should determine whether the modified questionnaire can provide better diagnostic accuracy and psychometric properties. The results of this study may assist in ruling in or out CTS diagnosis to a wide variety of target audience, such as hand specialists, physical and occupational therapists, as well as family doctors.
Experiencing earthquake in the first trimester of the fetal life increases subsequent diabetes risk in the adulthood: a cross-sectional study
Authors: Li Na , Song Mei , Wang Lan , Zhao Xiao-chuan , Wang Ran , Gao Yuan-yuan , Yu Lu-lu , An Cui-xia , Wang Xue-yi
Published: November 2020

Objective

To investigate the long-term effect of prenatal exposure to earthquake stress on diabetes risk in the adulthood.

Methods

This study included employees of Tangshan Kailuan Mining Group between July 29, 1976 and April 28, 1977. The exposure group included subjects who experienced the Tangshan Earthquake during their prenatal period and who had lived in Tangshan since birth. The non-exposure group included subjects who were born 1–1.9 years after the earthquake and who had lived in Tangshan since birth. A questionnaire was designed that included sociodemographic information, conditions during pregnancy, and earthquake experience. Anthropometric measurements including height and weight, body mass index (BMI), waist circumference were made. Fasting plasma glucose (FPG) and lipid profiles were also determined.

Results

Totally 947 subjects were included with 397 subjects in the exposed group and 550 subjects in the non-exposed group. The diabetes rate is significant different in these four groups(χ2 =8.045, P = 0.045). Moreover, 11.8, 7.5 and 8.0% of the subjects who were exposed to earthquake in the 1st, 2nd, and 3rd trimester of pregnancy had diabetes. 5.1% of the subjects had diabetes in non-exposure group. Our multivariate analysis showed that 1st trimester (OR 2.481, 95%CI 1.02, 6.034; P = 0.045) and loss of family members during earthquake (OR 2.452, 95%CI 1.293, 4.653; P = 0.006) were associated with significantly increased risk of diabetes.

Conclusions

Exposure to earthquake during the first trimester of pregnancy and experience of family member loss in the earthquake significantly increased the subsequent risk of diabetes in the middle age (36–39 years of age). Our data suggest that earthquake experience in the early pregnancy has a longer-term effect on diabetes risk during adulthood.
Combined thrombogenic effects of vessel injury, pregnancy and procoagulant immune globulin administration in mice
Authors: Xu Yanqun , Liang Yideng , Parunov Leonid , Despres Daryl , Eckhaus Michael , Scott Dorothy , Ovanesov Mikhail , Struble Evi B.
Published: November 2020

Background

Pregnant women are at increased risk of thrombotic adverse events. Plasma derived immune globulin (IG) products, which are used in pregnancy for various indications, may contain procoagulant impurity activated coagulation factor XI (FXIa). Procoagulant IG products have been associated with increased thrombogenicity but their effect in pregnancy is unknown.

Methods

Late pregnant (gestation days 17–20) or early lactation (days 1–3) and control female mice were treated with IGs supplemented with human FXIa then subjected to ferric chloride (FeCl3) vessel injury. Occlusion of blood vessel was assessed by recording blood velocity in the femoral vein for 20 min using doppler ultrasound laser imaging. FXIa dose was selected by the ability to increase thrombin generation in mouse plasma in vitro.

Results

FXIa produced robust thrombin generation in mouse plasma ex vivo. Following FeCl3injury, pregnant and non-pregnant mice receiving IG + FXIa exhibited faster reduction of blood velocity in femoral vein compared to IG alone or untreated controls. In vitro, thrombin generation in plasma samples collected after thrombosis in FXIa-treated animals was elevated and could be reduced by anti-FXI antibody.

Conclusions

Our results suggest that intravenously-administered FXIa may contribute to thrombosis at the site of vascular injury in both pregnant and non-pregnant animals.
Molecular characterization of breast cancer: a potential novel immune-related lncRNAs signature
Authors: Lai Jianguo , Chen Bo , Zhang Guochun , Li Xuerui , Mok Hsiaopei , Liao Ning
Published: November 2020

Background

Accumulating evidence has demonstrated that immune-related lncRNAs (IRLs) are commonly aberrantly expressed in breast cancer (BC). Thus, we aimed to establish an IRL-based tool to improve prognosis prediction in BC patients.

Methods

We obtained IRL expression profiles in large BC cohorts (N = 911) from The Cancer Genome Atlas (TCGA) database. Then, in light of the correlation between each IRL and recurrence-free survival (RFS), we screened prognostic IRL signatures to construct a novel RFS nomogram via a Cox regression model. Subsequently, the performance of the IRL-based model was evaluated through discrimination, calibration ability, risk stratification ability and decision curve analysis (DCA).

Results

A total of 52 IRLs were obtained from TCGA. Based on multivariate Cox regression analyses, four IRLs (A1BG-AS1, AC004477.3, AC004585.1 and AC004854.2) and two risk parameters (tumor subtype and TNM stage) were utilized as independent indicators to develop a novel prognostic model. In terms of predictive accuracy, the IRL-based model was distinctly superior to the TNM staging system (AUC: 0.728 VS 0.673,P = 0.010). DCA indicated that our nomogram had favorable clinical practicability. In addition, risk stratification analysis showed that the IRL-based tool efficiently divided BC patients into high- and low-risk groups (P < 0.001).

Conclusions

A novel IRL-based model was constructed to predict the risk of 5-year RFS in BC. Our model can improve the predictive power of the TNM staging system and identify high-risk patients with tumor recurrence to implement more appropriate treatment strategies.
Low-volume high-intensity interval training improves cardiometabolic health, work ability and well-being in severely obese individuals: a randomized-controlled trial sub-study
Authors: Reljic Dejan , Frenk Fabienne , Herrmann Hans J. , Neurath Markus F. , Zopf Yurdagül
Published: November 2020

Background

Obesity is associated with impaired health and lower work ability. Increased physical activity is a cornerstone in the treatment of obesity and related risk factors. Recently, high-intensity interval training (HIIT) has emerged as a popular exercise option. However, data regarding the effects on cardiometabolic health, perceived work ability and well-being in severely obese individuals are lacking.

Methods

Sixty-five obese individuals with sedentary occupation (48.7 ± 9.9 years, BMI: 39.6 ± 7.1 kg/m2) were randomly allocated to an extremely time-efficient HIIT (5 × 1 min at 80–95% maximal heart rate on cycle ergometers, 2×/week for 12 weeks) or an inactive control group (CON). Both groups received nutritional counseling to support weight loss. Primary outcome was maximal oxygen uptake (VO2max), secondary outcomes were cardiometabolic risk indices, body composition, work ability index (WAI), quality of life (QoL, EQ-5D-5L-questionnaire) and perceived stress (PSQ-questionnaire).

Results

Mean body weight reduction was 5.3 kg [95% confidence interval (95% CI) − 7.3 to − 3.3 kg] in the HIIT group (P < 0.001) and 3.7 kg (95% CI − 5.3 to − 2.1 kg) in CON (P < 0.001), respectively. Only the HIIT group showed significant (P < 0.001) changes in VO2max [+ 3.5 mL/kg/min (95% CI 2.5 to 4.6 mL/kg/min)], waist circumference [–7.5 cm (95% CI − 9.8 to − 5.1 kg)], mean arterial blood pressure [− 11 mmHg (95% CI − 14 to − 8 mmHg)], WAI [+ 3.0 points (95% CI 1.7 to 4.3 points)] and QoL [+ 10% (95% CI 5 to 16%)]. In CON, none of these parameters improved significantly.

Conclusions

Low-volume HIIT may induce significant improvements in cardiometabolic health, especially VO2max, WAI and well-being in obese individuals after only 12 weeks. Our results underpin the wide range of benefits on health and subjective measures through exercise that go well beyond simple weight loss through dietary restriction alone.

Trial registration: ClinicalTrials.gov Id: NCT03306069. Registered 10 October 2017, https://clinicaltrials.gov/ct2/show/NCT03306069.
A brief guide to the science and art of writing manuscripts in biomedicine
Authors: Forero Diego A. , Lopez-Leon Sandra , Perry George
Published: November 2020

Publishing articles in international scientific journals is the primary method for the communication of validated research findings and ideas. Journal articles are commonly used as a major input for evaluations of researchers and institutions. Few articles have been published previously about the different aspects needed for writing high-quality articles. In this manuscript, we provide an updated and brief guide for the multiple dimensions needed for writing manuscripts in the health and biological sciences, from current, international and interdisciplinary perspectives and from our expertise as authors, peer reviewers and editors. We provide key suggestions for writing major sections of the manuscript (e.g. title, abstract, introduction, methods, results and discussion), for submitting the manuscript and bring an overview of the peer review process and  of the post-publication impact of the articles.
Transcriptome analysis identifies putative multi-gene signature distinguishing benign and malignant pancreatic head mass
Authors: Chhatriya Bishnupriya , Mukherjee Moumita , Ray Sukanta , Saha Barsha , Lahiri Somdatta , Halder Sandip , Ghosh Indranil , Khamrui Sujan , Das Kshaunish , Bhattacharjee Samsiddhi , Mohapatra Saroj Kant , Goswami Srikanta
Published: November 2020

Background

Most often, the patients with pancreatic diseases are presented with a mass in pancreatic head region and existing methods of diagnosis fail to confirm whether the head mass is malignant or benign. As subsequent management of the disease hugely depends on the correct diagnosis, we wanted to explore possible biomarkers which could distinguish benign and malignant pancreatic head masses.

Methods

In order to address that gap, we performed a case–control study to identify genome-wide differentially expressed coding and noncoding genes between pancreatic tissues collected from benign and malignant head masses. These genes were next shortlisted using stringent criteria followed by selection of top malignancy specific genes. They subsequently got validated by quantitative RT-PCR and also in other patient cohorts. Survival analysis and ROC analysis were also performed.

Results

We identified 55 coding and 13 noncoding genes specific for malignant pancreatic head masses. Further shortlisting and validation, however, resulted in 5 coding genes as part of malignancy specific multi-gene signature, which was validated in three independent patient cohorts of 145 normal and 153 PDAC patients. We also found that overexpression of these genes resulted in survival disadvantage in the patients and ROC analysis identified that combination of 5 coding genes had the AUROC of 0.94, making them potential biomarker.

Conclusions

Our study identified a multi-gene signature comprising of 5 coding genes (CDCA7,DLGAP5,FOXM1,TPX2andOSBPL3) to distinguish malignant head masses from benign ones.
Technical note: factors affecting dose distribution in the overlap region of two-segment total body irradiation by helical tomotherapy
Authors: Wang HaiYang , Liu JunQi , Pi YiFei , Liu Qi , Mi Yang , Yang XiangXiang , Guo YueXin , Fan RuiTai
Published: November 2020

Objective

To assess the effects of various treatment planning parameters to identify the optimal gap distance for precise two-segment total body irradiation (TBI) using helical tomotherapy (HT) with fixed jaw mode.

Methods and materials

Data of a treatment plan for 8 acute leukemia patients (height range: 109–130 cm) were analyzed. All patients underwent total-body computed tomography (CT) with 5-mm slice thickness. A lead wire, placed at 10 cm above the patella, was used to mark the boundary between the two segments. Target volumes and organs at risk were delineated using a Varian Eclipse 10.0 physician’s workstation. Different distances between the lead wire and the boundary of the two targets were used. CT images were transferred to the HT workstation to design the treatment plans, by adjusting parameters, including the field width (FW; 2.5 cm, and 5 cm), pitch (0.287 and 0.430), modulation factor (1.8). The plans were superimposed to analyze the dose distributions in the overlap region when varying target gap distances, FWs, pitches to determine the optimal combinations.

Results

The pitch did not affect the dose distribution in the overlap region. The dose distribution in the overlap region was mostly homogeneous when the target gap distance was equal to the FW. Increased FW diminished the effect of the target gap distance on the heterogeneous index of the overlap region.

Conclusions

In two-segment TBI treatments by HT with Helix mode, a gap distance equal to the FW may achieve optimal dose distribution in the overlap region.
Per-fraction positional and dosimetric performance of prone breast tangential radiotherapy on Halcyon™ linear accelerator assessed with daily rapid kilo-voltage cone beam computed tomography: a single-institution pilot study
Authors: Yoon Suk W. , Taunk Neil K. , Freedman Gary M. , Hubley Emily , O’Reilly Shannon , Teo Boon- Keng K. , Anamalayil Shibu , Dong Lei , Kennedy Christopher , Zou Wei , Metz James M. , Li Taoran
Published: November 2020

Background

This study investigates daily breast geometry and delivered dose to prone-positioned patients undergoing tangential whole breast radiation therapy (WBRT) on an O-ring linear accelerator with 6X flattening filter free mode (6X-FFF), planned with electronic compensation (ECOMP) method. Most practices rely on skin marks or daily planar image matching for prone breast WBRT. This system provides low dose daily CBCT, which was used to study daily robustness of delivered dose parameters for prone-positioned WBRT.

Methods

Eight patients treated with 16-fraction prone-breast WBRT were retrospectively studied. Planning CTs were deformed to daily CBCT to generate daily synthetic CTs, on which delivered dose distributions were calculated. A total of 8 × 16 = 128 synthetic CTs were generated. Consensus ASTRO definition was used to contour Breast PTV Eval for each daily deformed CT. Breast PTV Eval coverage (V90%) and hotspot (V105% and Dmax) were monitored daily to compare prescription dose with daily delivered dose. Various predictors including patient weight, breast width diameter (BWD), and Dice similarity coefficient (DSC) were fit into an analysis of covariance model predicting V90% and V105% deviation from prescribed (ΔV90%, ΔV105%). Statistical significance is indicated with asterisks (* forp < 0.05; ** forp < 0.001).

Results

Daily delivered Breast PTV Eval V90% was moderately smaller than prescribed (median ΔV90% = − 0.1%*), while V105% was much larger (median ΔV105% = + 10.1%** or + 92.4 cc**). Patient’s weight loss correlated with significantly increased ΔV105% (+ 4.6%/ − 1% weight, R2 = 0.4**) and moderately decreased ΔV90% (− 0.071%/ − 1% wt., R2 = 0.2**). Comprehensive ANCOVA models indicated three factors affect ΔV90% and ΔV105% the most: (1) BWD decrease (− 0.09%* and + 10%**/ − 1 cm respectively), (2) PTV Eval volume decrease (− 0.4%** and + 9%**/ − 100 cc), and for ΔV105% only, (3) the extent of breast deformation (+ 10%**/ − 0.01 DSC). Breast PTV Eval volume also decreased with time (− 2.21*cc/fx), possibly indicating seroma resolution and increase in V105% over time.

Conclusions

Daily CBCT revealed key delivered dose parameters vary significantly for patients undergoing tangential prone breast WBRT planned with ECOMP using 6X-FFF. Patient weight, BWD, and breast shape deformation could be used to predict dosimetric variations from prescribed. Preliminary findings suggest an adaptive plan based on daily CBCT could reduce excessive dose to the breast.
Modern treatment outcomes for early T-stage oropharyngeal cancer treated with intensity-modulated radiation therapy at a tertiary care institution
Authors: Di Gravio Eric J. , Lang Pencilla , Kim Hugh Andrew Jinwook , Chinnery Tricia , Mundi Neil , MacNeil S. Danielle , Mendez Adrian , Yoo John , Fung Kevin , Mymryk Joe S. , Barrett John W. , Read Nancy , Venkatesan Varagur , Kuruvilla Sara , Mendez Lucas C. , Winquist Eric , Mitchell Sylvia , Mattonen Sarah A. , Nichols Anthony C. , Palma David A.
Published: November 2020

Background

Transoral surgery (TOS), particularly transoral robotic surgery (TORS) has become the preferred modality in the United States for the treatment of early stage oropharyngeal cancer, largely due to assumptions of fewer toxicities and improved quality of life compared to primary radiotherapy (RT). However, these assumptions are based on retrospective analysis, a subset of which utilize primary RT groups not limited to T1-2 stage tumors for which transoral robotic surgery is FDA approved. Thus, there is potential for underestimating survival and overestimating toxicity, including treatment related mortality, in primary RT.

Methods

Consecutive cases of early T-stage (T1–T2) oropharyngeal cancer presenting to the London Health Sciences Centre between 2014 and 2018 treated with RT or chemoradiation (CRT) were reviewed. Patient demographics, treatment details, survival outcomes and toxicity were collected. Toxicities were retrospectively graded using the Common Terminology Criteria for Adverse Events criteria.

Results

A total of 198 patients were identified, of which 82% were male and 73% were HPV-positive. Sixty-eight percent of patients experienced a grade 2 toxicity, 48% a grade 3 and 4% a grade 4. The most frequent toxicities were dysphagia, neutropenia and ototoxicity. The rates of gastrostomy tube dependence at 1 and 2 years were 2.5% and 1% respectively. There were no grade 5 (fatal) toxicities. HPV-positive patients experienced improved 5-year overall survival (86% vs 64%, p = 0.0026).

Conclusions

Primary RT or CRT provides outstanding survival for early T-stage disease, with low rates of severe toxicity and feeding tube dependence. This study provides a reference for comparison for patients treated with primary transoral surgery.
Outcome of lung metastases due to bone giant cell tumor initially managed with observation
Authors: Tsukamoto Shinji , Ciani Giovanni , Mavrogenis Andreas F. , Ferrari Cristina , Akahane Manabu , Tanaka Yasuhito , Rocca Michele , Longhi Alessandra , Errani Costantino
Published: November 2020

Background

The outcomes of patients with lung metastases from giant cell tumor of bone (GCTB) vary from spontaneous regression to uncontrolled growth. To investigate whether observation is an appropriate first-line management approach for patients with lung metastases from GCTB, we evaluated the outcomes of patients who were initially managed by observation.

Methods

We retrospectively reviewed the data of 22 patients with lung metastases from histologically confirmed GCTB who received observation as a first-line treatment approach. The median follow-up period was 116 months.

Results

Disease progression occurred in 12 patients (54.5%). The median interval between the discovery of lung metastases and progression was 8 months. Eight patients underwent metastasectomy following initial observation. The median interval between the discovery of lung metastases and treatment by metastasectomy was 13.5 months. None of the patients experienced spontaneous regression. Of the 22 patients, 36.4% needed a metastasectomy, and 9.1% required denosumab treatment during the course of the follow-up period. Disease progression occurred in 45.5% of the 11 patients with lung nodules ≤ 5 mm, while all five of the patients with lung nodules > 5 mm experienced disease progression. Progression-free survival was significantly worse in the group with lung nodules > 5 mm compared to the group with lung nodules ≤ 5 mm (p= 0.022).

Conclusions

Observation is a safe first-line method of managing patients with lung metastases from GCTB. According to radiological imaging, approximately half of the patients progressed, and approximately half required a metastasectomy or denosumab treatment. However, patients with lung nodules > 5 mm should receive careful observation because of the high rate of disease progression in this group.
Assessing the effect of Gotfried reduction with positive buttress pattern in the young femoral neck fracture
Authors: Huang Kai , Fang Xiaohui , Li Guijun , Yue Jiajun
Published: November 2020

Background

Although many available surgical procedures for displaced femoral neck fractures in young patients, there are still many challenges to achieve satisfactory results. The incidence of avascular necrosis and nonunion rates remains relatively high despite the progress in our understanding and surgical technique. The purpose of this study was to evaluate the clinical efficacy of Gotfried reduction and cannulated screw fixation in the treatment of femoral neck fracture for young adults.

Methods

A retrospective analysis was made on 67 cases from May 2013 to March 2019. They were divided into three groups according to the first postoperative anteroposterior view of hip X-ray: Anatomic reduction (group A), Gotfried positive buttress reduction (group B), and Gotfried negative buttress reduction (group C). The incidence of avascular osteonecrosis of the femoral head (AVN) and the Harris scores of hip joints were compared in three groups at the last follow-up.

Results

The mean follow-up period after surgery was 22.5 ± 11.3 (range, 11–34) months. There were 21 cases (mean age, 49.7 ± 11.6) in group A, 24 cases (mean age, 48.6 ± 11.3) in group B, 22 cases (mean age, 48.3 ± 12.4) in group C. No significant difference in general preoperative demographics (P > 0.05). The incidence of avascular necrosis of femoral head in group A, B, and C was 19.05%, 20.83%, and 22.73%, respectively, showing no significant difference between groups (P = 0.156). The mean Harris hip scores at the final follow-up for groups A (85.6 ± 6.7) and B (84.5 ± 6.2) were significantly higher than group C (74.3 ± 8.3), and the difference was statistically significant (P = 0.043). The incidence of femoral neck shortening in group A and group B was significantly lower than that in group C in postoperative 1 year, and the difference was statistically significant (P < 0.05).

Conclusions

Gotfried positive buttress reduction and fixation for femoral neck fracture may lead to similar clinical results with anatomic reduction, but much better than Gotfried negative buttress reduction. For the patients of femoral neck fracture with severe displacement and difficulty reduction, it is not necessary to pursue anatomical reduction. Achieving positive valgus reduction can also obtain satisfactory clinical results, and should try to avoid negative buttress.
Chronic lymphedema in patients with kaposiform hemangioendothelioma: incidence, clinical features, risk factors and management
Authors: Ji Yi , Chen Siyuan , Xia Chuncao , Zhou Jiangyuan , Jiang Xian , Xu Xuewen , Yang Kaiying , Zhang Xuepeng , Kong Feiteng , Lu Guoyan , Zhang Yongbo
Published: November 2020

Objectives

There are no cohort studies of chronic lymphedema in patients with kaposiform hemangioendothelioma (KHE). We sought to characterize the incidence, clinical features, risk factors and management of chronic lymphedema in patients with KHE.

Methods

We conducted a multicenter retrospective analysis of patients who had a minimum of 3 years of follow-up after the onset of KHE and/or Kasabach–Merritt phenomenon (KMP). Clinical features were reviewed to determine the possible cause of chronic lymphedema. The degree of lymphedema, risk factors and management strategies were analyzed.

Results

Among the 118 patients, chronic lymphedema was confirmed by lymphoscintigraphy 1 year after the onset of KHE and/or KMP in 13 patients. In 8 patients with lymphedema, extremity swelling was evident in the presence of KHE and/or KMP. In all patients with lymphedema, a unilateral extremity was affected, along with ipsilateral KHE. Most (84.6%) patients reported moderate lymphedema. Lymphedema was more common in patients with larger (≥ 10 cm) and mixed lesions involving the extremities (P < 0.01). A history of KMP and sirolimus treatment were not predictors of lymphedema (P > 0.05). Overall, 76.9% of patients received sirolimus treatment after referral, including 53.8% who presented extremity swelling before referral. Seven (53.8%) patients received compression therapy. Five (38.5%) patients reported lymphedema-associated decreased range of motion at the last follow-up.

Conclusions

Chronic lymphedema is a common sequela of KHE and can occur independently of KMP and sirolimus treatment. Patients with large and mixed KHE involving extremities should be closely monitored for this disabling complication.