bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrent gastric cancer sustaining a partial response after the nivolumab discontinuation because of immune-related adverse events: a case report
Authors: Arigami Takaaki , Matsushita Daisuke , Okubo Keishi , Tanaka Takako , Sasaki Ken , Noda Masahiro , Kita Yoshiaki , Mori Shinichiro , Tsuruda Yusuke , Kurahara Hiroshi , Ohtsuka Takao 
Published: June 2020

Abstract
Background: The prognosis of patients with recurrent gastric cancer is extremely poor despite chemotherapy being clinically recommended as the first therapeutic strategy. Recent clinical trials have established the clinical utility of nivolumab in the third-line treatment of such patients. Remarkably, immune-related adverse events (irAE) have been focused as a promising predictor for tumor response to nivolumab. This report aims to present a long-term survivor of recurrent gastric cancer who was followed up without any treatments after the nivolumab discontinuation because of irAE.Case presentation: A 65-year-old male with stage III gastric cancer (cT4aN1M0) underwent distal gastrectomy and a partial resection of the transverse colon with D2 lymph node dissection after neoadjuvant chemotherapy. Owing to the final pathological stage IIIB (ypT4bN1M0), the patient received adjuvant chemotherapy. Nevertheless, during adjuvant chemotherapy 1-year post-surgery, computed tomography (CT) revealed lymph node swelling in station no. 9. Thus, upon diagnosis with lymph node recurrence, the patient was treated with two courses of capecitabine + oxaliplatin and three courses of ramucirumab + paclitaxel as the first- and second-line regimens, respectively. Based on these regimens, the patient had a progressive disease to chemotherapy. Consequently, we administered nivolumab 3 mg/kg intravenously every 2 weeks and 240 mg/kg intravenously every 2 weeks after September 2018 as the third-line regimen. After four courses of nivolumab, CT revealed a significant shrinkage of the metastatic lymph node, with a 45.6% reduction. We confirmed a partial response during 11 courses of nivolumab. Since the occurrence of grade 4 diabetes mellitus after 12 courses of nivolumab, the patient was followed up without any treatment after the nivolumab discontinuation. Currently, the patient remains a partial response for 15 months since the nivolumab discontinuation and is alive for 31 months after disease recurrence.Conclusions: Acute irAE during nivolumab chemotherapy could be one of the crucial clinical factors to predict tumor suppression in patients with advanced gastric cancer.
Systemic inflammation-based predictors of pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients: A propensity score matching analysis
Authors: Xu Ning , Li Wenliang , Huang Fengchang , Yang Jun , Wen Zhengqi , Yin Liang , Zhang Yunfei , Zhao Jingjiao , Zhou Ruize , Yang Jingyu 
Published: June 2020

Abstract
Background: In the management of locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CRT), the relationship between systemic inflammation-based predictors and tumor response remains unclear. This study aimed to determine whether these inflammatory factors can predict tumor response.Methods: Totally 205 LARC patients underwent neoadjuvant CRT and curative surgery between 2008 and 2017 were analyzed. After propensity score matching, 146 patients (73 matched pairs) were enrolled in this study. The hematological parameters were collected and their relationship with tumor response was investigated.Results: After propensity score matching, the neutrophil-lymphocyte-ratio (NLR) and platelet-lymphocyte-ratio (PLR) before CRT in good response group were significantly lower than those in poor response group, while there was no significant difference in all hematological characteristics between two groups after CRT. The cutoff values​​ of pre-CRT NLR and pre-CRT PLR were 3.10 and 198.7 after receiver operating characteristic analysis. Multivariate analysis model indicated that pre-CRT PLR was not related with tumor response, while pre-CRT NLR≥3.1 was the predictor of poor tumor response (OR=2.047, 95%CI =1.241-3.377, p=0.005). Besides, patients with NLR≥3.1 had a significantly poor tumor regression grade rates compared with patients with NLR<3.1 (p=0.036).Conclusion: The increased NLR before CRT can be regarded as a hematological factor for poor tumor response in LARC, and higher NLR also represents worse tumor regression grade.
Impact of Visceral Obesity on Chronic Obstipation, Inflammation, Immune Function and Cognitive Function Among Patients with Inflammatory Bowel Disease
Authors: Wan Yemin , Zhang Dan , Qian Yunzhi , Chang Shuchen , Qian Haihua 
Published: June 2020

Abstract
Background: Obesity has gained attention among patients with inflammatory bowel disease (IBD). The impact of visceral obesity on chronic obstipation, inflammation, immune function and cognition after diagnosis of IBD is still unknown.Methods: This is a cross-sectional study of 140 IBD patients. Patients’ visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured by abdominal computerized tomography (CT) scans and were grouped according to visceral obesity. Baseline variables, chronic obstipation status, inflammation status and immune function were compared. The implications of visceral obesity on cognitive function were evaluated using Mini-Mental State Examination (MMSE).Results: The prevalence of visceral obesity was 51% (37 out of 72) for CD patients and 26% for UC patients (18 out of 68 patients). CD patients with visceral obesity has higher incidence of chronic obstipation (81% vs. 57%, P = 0.028), higher IL-6 levels (9.3 vs. 6.0 pg/ml, P = 0.045) and lower CD4+ T cells (32.7% vs. 44.0%, P = 0.034). For UC patients, patients with visceral obesity have the tendency of higher IL-6 levels (7.2 vs. 6.0 pg/ml, P = 0.053).Conclusion: IBD patients had high risks of visceral obesity. Patients with visceral obesity had higher prevalence of chronic obstipation, higher inflammation levels, decreased immune function.
Long-Term Effect of Periodic Transcranial Direct Current Stimulation and Manual Therapy Program in Fibromyalgia Syndrome: A Case Report
Authors: Danazumi Musa Sani , Yakasai Abdulsalam Mohammed , Ibrahim Shehu Usman , Abubakar Mubarak Falke 
Published: June 2020

Abstract
Purpose of the Study: This case report describes the management of a fibromyalgia patient using Periodic Transcranial Direct Current Stimulation (tDCS) and Manual Therapy (MT). Materials and Methods: A 41-year-old woman presented with a complaint of generalized body pain and fatigue which started 10 years ago. The pain was associated with mood changes and insomnia among other symptoms, and was not responsive to analgesics and traditional herbal medicine. The patient was diagnosed as having FMS. Three sets of anodal tDCS for 20 minutes each with an interval of 10 minutes between successive stimulations followed by 30 minutes of MT were administered on each treatment day. The treatment was given 2 times per week for 8 weeks, totaling 16 hours of tDCS and 8 hours of MT. Outcomes were assessed at baseline (T0), at 1 (T1) and 2 months (T2) of intervention, and then at 4 (T3), 6 (T4) and 12 months (T5) of follow-up. Results: At 12 month follow-up (T5), outcomes indicated improvement in all symptoms (WPI=0, SS=0, FIQ=0, BPI=0, MFI-20=20, MOS=0, MASQ=38, SF-36=87, HADS=3). Conclusion: Periodic tDCS followed by MT may be used to enhance long-term remission of symptoms in a patient with FMS.
Effect of Favipiravir and an Anti-inflammatory Strategy for COVID-19
Authors: Yamamura Hitoshi , Matsuura Hiroshi , Nakagawa Junichiro , Fukuoka Hiroshi , Domi Hisaya , Chujoh Satoru 
Published: June 2020

Abstract
We attempted the cocktail treatment of favipiravir, steroid, and heparin for COVID-19. This study aimed to evaluate the effect of cocktail therapy for severe COVID-19.The treatment protocol was as follows: oral favipiravir (3600 mg on Day 1, 1600 mg from day 2 to day 14), methylprednisolone (1000 mg for 3 days), and low molecular weight (2000 IU every 12 h) or unfractionated heparin (10,000-12,000 IU/day). Thirteen patients with COVID-19 requiring mechanical ventilation were admitted during the study period. Mean patient age was 63 (range, 46-80) years, and 69.0% were men. Only one patient required extracorporeal membrane oxygenation. Time from first symptom appearance to favipiravir administration was 8.7 (range, 4-13) days. The P/F ratio changed very little over the first 6 days and then gradually recovered. The Interleukin-6 peaked on Day 4 and decreased thereafter. Presepsin also peaked on Day 3, remained about the same until Day 6, and then decreased. The clinical course of SARS-CoV-2 treatment with the cocktail in mechanically ventilated patients with COVID-19 indicated that favipiravir could partially control inflammatory mediators but could not completely control them or respiratory status.
The Application of CRISPR/Cas9 System in Cervical Precancerous Lesions
Authors: Gao Chun , Wu Ping , Yu Lan , Liu Liting , Liu Hong , Tan Xiangyu , Wang Liming , Huang Xiaoyuan , Wang Hui 
Published: June 2020

Abstract
Background : The clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system is becoming a promising gene therapy method. Herein, we evaluated the therapeutic effect of CRISPR/Cas9 system in cervical carcinogenesis, especially cervical precancerous lesions. Methods : In cervical cancer/pre-cancer cell lines, we transfected the CRISPR/Cas9, transcription activator–like effector nuclease (TALEN), and zinc finger nuclease (ZFN) plasmids, respectively. We used the cell apoptosis, cell viability, and colony formation assays to examine the efficiency and specificity of inhibition of cell apoptosis and growth between the different gene editing tools. Western blotting was used to estimate the related protein expression. We used xenograft formation assays to examine the ability of inhibition of cell growth in vivo. In the K14-HPV16 transgenic mice model of HPV-driven cervical carcinogenesis, we investigated the therapeutic effect by vaginal administration. Results : Compared to ZFN and TALEN, CRISPR/Cas9 has shown comparable efficiency and specificity of inhibition of cell apoptosis and growth in cervical cancer cell lines, which seem to be more pronounced in the S12 cell line derived from the low-grade cervical lesion. In xenograft formation assays, CRISPR/Cas9 could inhibit tumor formation in vivo and affects the expression of the corresponding protein. In the K14-HPV16 transgenic mice, CRISPR/Cas9 treatment caused mutations of the E7 gene and restored the expression of RB, E2F1, and CDK2, thereby reversing the cervical carcinogenesis phenotype. Conclusion : In this study, we have demonstrated that CRISPR/Cas9 targeting HPV16 E7 could effectively reduce the expression of E7 protein in vitro. Additionally, it could revert the HPV-related cervical carcinogenesis in K14-HPV16 transgenic mice, which has shown great potential in clinical treatment.
The loss of flight in ant workers enabled an evolutionary redesign of the thorax for ground labour
Authors: Peeters Christian , Keller Roberto A. , Khalife Adam , Fischer Georg , Katzke Julian , Blanke Alexander , Economo Evan P. 
Published: June 2020

Abstract
Background

Explanations for the ecological dominance of ants generally focus on the benefits of division of labour and cooperation during foraging. However, the principal innovation of ants relative to their wasp ancestors was the evolution of a new phenotype: a wingless worker caste optimized for ground labour. Ant workers are famous for their ability to lift and carry heavy loads, but we know surprisingly little about the morphological basis of their strength. Here we examine the consequences of the universal loss of flight in ant workers on skeletomuscular adaptations in the thorax for enhanced foraging on six legs.

Results

Using X-ray microcomputed tomography and 3D segmentation, we compared winged queens and wingless workers in Euponera sikorae (subfamily Ponerinae) and Cataglyphis savignyi (subfamily Formicinae). Workers are characterized by five major changes to their thorax: i) fusion of the articulated flight thorax (queens) into a rigid box optimized to support the muscles that operate the head, legs and abdomen, ii) redesign of internal cuticular structures for better bracing and muscle attachment, iii) substantial enlargement of the neck muscles for suspending and moving the head, iv) lengthening of the external trochanter muscles, predominant for the leg actions that lift the body off the ground, v) modified angle of the petiole muscles that are key for flexion of the abdomen. We measured volumes and pennation angles for a few key muscles to assess their increased efficacy. Our comparisons of additional workers across five genera in subfamilies Dorylinae and Myrmicinae show these modifications in the wingless thorax to be consistent. In contrast, a mutillid wasp showed a different pattern of muscle adaptations as a result of the lack of wing muscles.

Conclusions

Rather than simply a subtraction of costly flight muscles, we propose the ant worker thorax evolved into a power core underlying stronger mandibles, legs, and sting. This contrasts with solitary flightless insects where the lack of central place foraging generated distinct selective pressures for rearranging the thorax. Stronger emphasis is needed on innovations of social insects as individuals at the phenotypic level to further our understanding of the evolution of social behaviours.
Intraoperative hypotension is not associated with adverse short-term postoperative outcomes after esophagectomy in esophageal cancer patients
Authors: Yeheyis Ephraim Teffera , Kassa Seyoum , Yeshitila Hiwot , Bekele Abebe 
Published: June 2020

Abstract
Background

The effect of low systolic blood pressure and its subsequent postoperative outcome during esophagectomy for esophageal cancer is not well studied.

Methods

Prospective study was conducted and data were collected on patients who underwent esophagectomy and esophagogastrostomy for esophageal cancer. Intraoperative Hypotension (IOH), defined as Systolic Blood Pressure (SBP) < 90 mm Hg lasting more than 5 minutes, was recorded. Patients’ 30 days post-operative composite outcome of mortality, anastomotic leak and prolonged hospital stay were analyzed as outcome variables

Result

A total of 54 patients underwent esophagectomy for esophageal cancer during the study period. The mean age was 54 years. Mean duration of the surgery was 208 minutes. Intraoperative mean low SBP was 80mmHg while the lowest record was 55 mmHg. IOH occurred in 51 .2 % (n=29) of patients; of these, 7.4% (n=4) had anastomotic leak (OR 1.2, 95% CI 0.26-6.3; p=0.76) , mortality was 5.5% (n=3) (OR 1.44, 95% CI 0.22- 9.3; p =0.7) and 33 % (n=18) had prolonged hospital stay (OR 0.53, 95% CI 0.14- 1.9; p=0.34 ).Over all anastomotic leak rate was 13% (n=7). The 30 days operative mortality was 9.2% and 55 % (30) of patients had prolonged hospital stay. Multivariate analysis (logistic regression model) showed SBP < 90mmHg for more than 5 minutes was not significantly associated either with individual or composite out comes of mortality, anastomotic leak and prolonged hospital stay (AOR 1.06 ,95% CI 0.98-1.14; p=0.16)

Conclusion

In patients undergoing esophagectomy for esophageal cancer, a systolic blood pressure < 90 mm Hg for greater than 5 min during surgery has no significant statistical association either with individual or composite adverse outcomes of mortality, anastomotic leak and prolonged hospital stay.
Ergogenic effect of pre-exercise chicken broth ingestion on a high-intensity cycling time-trial
Authors: Barbaresi Silvia , Blancquaert Laura , Nikolovski Zoran , de Jager Sarah , Wilson Mathew , Everaert Inge , De Baere Siegrid , Croubels Siska , De Smet Stefaan , Cable Tim , Derave Wim 
Published: June 2020

Abstract
Background Chicken meat extract is a popular functional food in Asia. It is rich in the bioactive compounds carnosine and anserine, two histidine-containing dipeptides (HCD). Studies suggest that acute pre-exercise ingestion of chicken extracts has important applications towards exercise performance and fatigue control, but the evidence is equivocal. This study aimed to evaluate the ergogenic potential of the pre-exercise ingestion of a homemade chicken broth (CB) vs a placebo soup on a short-lasting, high-intensity cycling exercise. Methods Fourteen men participated in this double-blind, placebo-controlled, crossover intervention study. Subjects ingested either CB, thereby receiving 46.4 mg/kg body weight of HCD, or a placebo soup (similar in taste without HCD) 40min before an 8min cycling time trial (TT) was performed. Venous blood samples were collected at arrival (fasted), before exercise and at 5min recovery. Plasma HCD were measured with UPLC-MS/MS and glutathione (in red blood cells) was measured through HPLC. Capillary blood samples were collected at different timepoints before and after exercise. Results A significant improvement (p=0.033; 5.2%) of the 8min TT mean power was observed after CB supplementation compared to placebo. Post-exercise plasma carnosine (p<0.05) and anserine (p<0.001) was significantly increased after CB supplementation and not following placebo. No significant effect of CB supplementation was observed either on blood glutathione levels, nor on capillary blood analysis. Conclusions Oral CB supplementation improved the 8min TT performance albeit it did not affect the acid-base balance or oxidative status parameters. Further research should unravel the potential role and mechanisms of HCD, present in CB, in this ergogenic approach.
SYBR-Green-Based Quantitative Real-Time PCR for Discriminating Between Closely Related Angiostrongylus Cantonensis and A. Malaysisensis
Authors: Jakkul Wallop , Chaisiri Kittipong , Saralamba Naowarat , Limpanont Yanin , Dusitsittipon Sirilak , Charoennitiwat Vachirapong , Thaenkham Urusa 
Published: June 2020

Abstract
Background: Angiostrongylus cantonensis is a well-known pathogen causing human angiostrongyliasis eosinophilic meningitis. Humans, as accidental hosts, are infected by eating undercooked snails containing third-stage larvae. A. malaysiensis is closely related to A. cantonensis and has been described as a potential human pathogen. Recently, the two species have been reported to have overlapping distributions in the same endemic area, particularly in the Indochina region. Because of their similar morphological characteristics, misidentification often occurs, particularly of the third-stage larva in the snail intermediate host. Methods: We designed species-specific primers to mitochondrial cytochrome b, which was used as a genetic marker. SYBR-green quantitative real-time PCR (qPCR) was employed to quantitatively detect and identify the third-stage larvae and tissue debris in the cerebrospinal fluid (CSF) of a patient, and to quantify third-stage larvae in the snail Achatina fulica collected from the field.Results: The newly designed primers were highly specific and sensitive, even when using conventional PCR. SYBR green qPCR quantitatively detected around 10−4 ng of genomic DNA from one larva and facilitated the specific detection and identification of parasitic genetic material from the CSF of a patient with angiostrongyliasis. The method also estimated the number of larvae in A. fulica and revealed that the primary source of Angiostrongylus infection in the King Rama IX public park study area was A. malaysiensis; although, the two Angiostrongylus species each infected 10% of the snails. Conclusions: Our SYBR green qPCR method is a useful and inexpensive technique for parasite identification and has sufficient sensitivity and specificity to detect a single larva and simultaneously discriminate between A. cantonensis and A. malaysiensis. The number of larvae infecting or co-infecting the snail intermediate host can also be estimated. In future research, this qPCR method could be employed in a molecular survey of A. cantonensis and A. malaysiensis occurrence within intermediate and definitive hosts. The technique should also be applied in a study analyzing CSF specimens from patients with eosinophilic meningitis to assess the usefulness of the method for clinical diagnosis.
Wolbachia Infection in Wild Mosquitoes (Diptera: Culicidae): Implications for Transmission Modes and Host-Endosymbiont Associations
Authors: Ding Huicong , Yeo Huiqing , Puniamoorthy Nalini 
Published: June 2020

Abstract
Background: Wolbachia is an intracellular bacterial endosymbiont found in most insect lineages. In mosquitoes, the endosymbiont’s influence on host reproduction and arboviral transmission has spurred numerous studies aimed at using Wolbachia-infection as a vector control technique. However, there exist several gaps in the literature regarding the natural Wolbachia infection across species, modes of transmission as well as the associations between various Wolbachia lineages and their hosts. This study aims to address these by exploring mosquito-Wolbachia associations and their evolutionary implications.Methods: We conducted tissue-specific PCR screening of Wolbachia infection in wild mosquitoes from Singapore using the wsp molecular marker. Tissues examined include leg, gut, and reproductive tissues. We also explored mosquito-Wolbachia associations using three methods – a tanglegram, distance-based, and event-based method, and inferred instances of vertical transmission and host shifts. Results: We screened 271 adult mosquitoes (41 species and 14 genera) for Wolbachia and found that 43.9% of all individuals harboured Wolbachia. Eight out of the 21 infected species were not previously reported. We detected Wolbachia infections predominantly in the reproductive tissues, a strong indication of vertical transmission. Despite this, Wolbachia infection rates vary widely within a mosquito host species. There was no clear signal of co-phylogeny between the mosquito hosts and the twelve putative Wolbachia strains observed in our study. Host shift events were also observed. Conclusions: Our results suggest that the mosquito-Wolbachia relationship is complex and that a combination of transmission modes and multiple evolutionary events likely explain the distribution of Wolbachia diversity observed across mosquito hosts. This has implications towards understanding Wolbachia’s diversity, ecology, and utility as a biocontrol method.