bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low serum estradiol levels are related to Mycobacterium avium complex lung disease: a cross-sectional study
Authors: Uwamino Yoshifumi , Nishimura Tomoyasu , Sato Yasunori , Tamizu Eiko , Asakura Takanori , Uno Shunsuke , Mori Masaaki , Fujiwara Hiroshi , Ishii Makoto , Kawabe Hiroshi , Murata Mitsuru , Hasegawa Naoki 
Published: December 2019

Abstract
Background
The risk factors for Mycobacterium avium complex lung disease (MAC-LD) are not well known. We hypothesized that low serum estradiol (E2) levels are related to MAC-LD as most patients with MAC-LD are postmenopausal women.

Methods
This cross-sectional study compared patients with MAC-LD and healthy controls. Study subjects were postmenopausal women aged 65 years or younger. Serum testosterone, dehydroepiandrosterone sulfate (DHEA-S), and E2 levels were measured and categorized as high or low based on median levels. We performed multivariate analysis, receiver operating characteristic (ROC) curve analysis, and age- and body mass index (BMI)-matched subgroup analysis to evaluate the association between low serum E2 levels and MAC-LD.
Additionally, using blood samples obtained for other clinical studies, the levels of sex steroid hormones were compared between age- and BMI-matched MAC-LD and bronchiectasis female patients without non-tuberculosis mycobacterial infections (non-NTM BE).

Results
Forty-two patients with MAC-LD and 91 healthy controls were included. The median E2 (2.20 pg/mL vs. 15.0 pg/mL, p < 0.001), testosterone (0.230 ng/L vs. 0.250 ng/L, p = 0.005), and DHEA-S (82.5 μg/dL vs. 114.0 μg/dL, p < 0.001) levels were lower in the MAC-LD group than in the control group. Multivariate analysis revealed that low serum E2 (adjusted odds ratio = 34.62, 95% confidence interval = 6.02–199.14) was independently related to MAC-LD, whereas low DHEA-S and testosterone were not. ROC analysis illustrated a strong relationship between low serum E2 levels and MAC-LD (area under the curve = 0.947, 95% confidence interval = 0.899–0.995). Even the age- and BMI-matched subgroup analysis of 17 MAC-LD patients and 17 healthy controls showed lower serum E2 in MAC-LD patients than in healthy controls. Additionally, serum E2 levels of 20 MAC-LD patients were lower than plasma E2 levels of 11 matched non-NTM BE patients (1.79 pg/mL vs. 11.0 pg/mL, p < 0.001).

Conclusions
Low serum E2 levels were strongly related to MAC-LD in postmenopausal women.
The effects of repetitive transcranial magnetic stimulation in older adults with mild cognitive impairment: a protocol for a randomized, controlled three-arm trial
Authors: Taylor Joy L. , Hambro Benjamin C. , Strossman Nicole D. , Bhatt Priyanka , Hernandez Beatriz , Ashford J. Wesson , Cheng Jauhtai Joseph , Iv Michael , Adamson Maheen M. , Lazzeroni Laura C. , McNerney Margaret Windy 
Published: December 2019

Abstract
Background
Mild Cognitive Impairment (MCI) carries a high risk of progression to Alzheimer’s disease (AD) dementia. Previous clinical trials testing whether cholinesterase inhibitors can slow the rate of progression from MCI to AD dementia have yielded disappointing results. However, recent studies of the effects of repetitive transcranial magnetic stimulation (rTMS) in AD have demonstrated improvements in cognitive function. Because few rTMS trials have been conducted in MCI, we designed a trial to test the short-term efficacy of rTMS in MCI. Yet, in both MCI and AD, we know little about what site of stimulation would be ideal for improving cognitive function. Therefore, two cortical sites will be investigated in this trial: (1) the dorsolateral prefrontal cortex (DLPFC), which has been well studied for treatment of major depressive disorder; and (2) the lateral parietal cortex (LPC), a novel site with connectivity to AD-relevant limbic regions.

Methods/design
In this single-site trial, we plan to enroll 99 participants with single or multi-domain amnestic MCI. We will randomize participants to one of three groups: (1) Active DLPFC rTMS; (2) Active LPC rTMS; and (3) Sham rTMS (evenly split between DLPFC and LPC locations). After completing 20 bilateral rTMS treatment sessions, participants will be followed for 6 months to test short-term efficacy and track durability of effects. The primary efficacy measure is the California Verbal Learning Test-II (CVLT-II), assessed 1 week after intervention. Secondary analyses will examine effects of rTMS on other cognitive measures, symptoms of depression, and brain function with respect to the site of stimulation. Finally, selected biomarkers will be analyzed to explore predictors of response and mechanisms of action.

Discussion
The primary aim of this trial is to test the short-term efficacy of rTMS in MCI. Additionally, the project will provide information on the durability of cognitive effects and potentially distinct effects of stimulating DLPFC versus LPC regions. Future efforts would be directed toward better understanding therapeutic mechanisms and optimizing rTMS for treatment of MCI. Ultimately, if rTMS can be utilized to slow the rate of progression to AD dementia, this will be a significant advancement in the field.

Trial registration
Clinical Trials NCT03331796. Registered 6 November 2017, https://clinicaltrials.gov/ct2/show/NCT03331796. All items from the World Health Organization Trial Registration Data Set are listed in Appendix A.

Protocol version
This report is based on version 1, approved by the DSMB on 30 November, 2017 and amended on 14 August, 2018 and 19 September, 2019.
Case report on novel mutation in SPAST gene in Polish family with spastic paraplegia
Authors: Klimkowicz-Mrowiec Aleksandra , Dziubek Anna , Sado Malgorzata , Karpiński Marek , Gorzkowska Agnieszka 
Published: December 2019

Abstract
Background
Hereditary spastic paraplegia is a large group of degenerative, neurological disorders characterized by progressive lower limb spasticity and weakness. The disease was investigated precisely but still clinicians often make incorrect or late diagnosis. Our aim was to investigate the genetic background and clinical phenotype of spastic paraplegia in large Polish family.

Case presentation
A 37 years old woman presented with 4-year history of walking difficulties. On neurological examination, she had signs of upper motor lesion in lower extremities. She denied sphincter dysfunction and her cognition was normal. Her family history was positive for individuals with gait problems. The initial diagnosis was familial spastic paraplegia. Genetic testing identified a novel mutation in SPAST gene. All available family members were examined and had genetic testing. The same mutation in SPAST gene was identified in other affected family members. All patients caring the mutation presented with different phenotypes.

Conclusion
This study presents a family with spastic paraplegia due to a novel mutation c.1390G›T(p.Glu464Term) in SPAST gene. Affected individuals showed a range of phenotypes that varied in their severity. This case report demonstrates, the signs of hereditary spastic paraplegia can be often misdiagnosed with other diseases. Therefore genetic testing should always be considered in patients with lower limb spasticity and positive family history in order to help to establish the correct diagnosis.
Effect of lymph node dissection on stage-specific survival in patients with upper urinary tract urothelial carcinoma treated with nephroureterectomy
Authors: Zhai Ting-Shuai , Jin Liang , Zhou Zhen , Liu Xiang , Liu Huan , Chen Wei , Lu Jing-Yi , Yao Xu-Dong , Feng Li-Ming , Ye Lin 
Published: December 2019

Abstract
Background
We aimed to estimate the stage-specific impact of lymph node dissection (LND) on survival for upper urinary tract urothelial carcinoma (UTUC) patients treated with nephroureterectomy (NU).

Methods
Overall, 7278 UTUC patients undergoing NU within the SEER database from 2004 to 2015 were identified. Kaplan-Meier plots illustrated overall survival (OS) and cancer-specific survival (CSS) rates according to LND status. Multivariable Cox regression analyses assessed the effect of LND on OS and CSS rates stratified by pathological tumor stage.

Results
LND was performed in 26.9% of patients, and in 18.6, 23.3, 31.2 and 45.9% for pT1, pT2, pT3 and pT4 patients, respectively (P <  0.001). In multivariable Cox regression analyses, LND was associated with a higher OS or CSS in UTUC patients with pT3 and pT4 disease (all P <  0.05), but failed to achieve independent predictor status in patients with pT1 and pT2 disease (all P > 0.05). LND with 1 to 3 regional lymph nodes removed was prone to a higher OS or CSS only in pT4 compared to no LND (both P <  0.01). LND with 4 or more regional lymph nodes removed predisposed to a higher OS or CSS in pT3 or pT4 (all P <  0.05).

Conclusions
The beneficial effect of LND especially LND with 4 or more regional lymph nodes removed on survival was evident in pT3/4 patients. LND can be considered for pT3 and pT4, for pT1/2 remains to be seen, both of which will be verified by further prospective studies.
Preoperative plasma fatty acid metabolites inform risk of prostate cancer progression and may be used for personalized patient stratification
Authors: Zoni Eugenio , Minoli Martina , Bovet Cédric , Wehrhan Anne , Piscuoglio Salvatore , Ng Charlotte K. Y. , Gray Peter C. , Spahn Martin , Thalmann George N. , Kruithof-de Julio Marianna 
Published: December 2019

AbstractBackgroundLittle is known about the relationship between the metabolite profile of plasma from pre-operative prostate cancer (PCa) patients and the risk of PCa progression. In this study we investigated the association between pre-operative plasma metabolites and risk of biochemical-, local- and metastatic-recurrence, with the aim of improving patient stratification.MethodsWe conducted a case-control study within a cohort of PCa patients recruited between 1996 and 2015. The age-matched primary cases (n = 33) were stratified in low risk, high risk without progression and high risk with progression as defined by the National Comprehensive Cancer Network. These samples were compared to metastatic (n = 9) and healthy controls (n = 10). The pre-operative plasma from primary cases and the plasma from metastatic patients and controls were assessed with untargeted metabolomics by LC-MS. The association between risk of progression and metabolite abundance was calculated using multivariate Cox proportional-hazard regression and the relationship between metabolites and outcome was calculated using median cut-off normalized values of metabolite abundance by Log-Rank test using the Kaplan Meier method.ResultsMedium-chain acylcarnitines (C6-C12) were positively associated with the risk of PSA progression (p = 0.036, median cut-off) while long-chain acylcarnitines (C14-C16) were inversely associated with local (p = 0.034) and bone progression (p = 0.0033). In primary cases, medium-chain acylcarnitines were positively associated with suberic acid, which also correlated with the risk of PSA progression (p = 0.032, Log-Rank test). In the metastatic samples, this effect was consistent for hexanoylcarnitine, L.octanoylcarnitine and decanoylcarnitine. Medium-chain acylcarnitines and suberic acid displayed the same inverse association with tryptophan, while indoleacetic acid, a breakdown product of tryptophan metabolism was strongly associated with PSA (p = 0.0081, Log-Rank test) and lymph node progression (p = 0.025, Log-Rank test). These data were consistent with the increased expression of indoleamine 2,3 dioxygenase (IDO1) in metastatic versus primary samples (p = 0.014). Finally, functional experiments revealed a synergistic effect of long chain fatty acids in combination with dihydrotestosterone administration on the transcription of androgen responsive genes.ConclusionsThis study strengthens the emerging link between fatty acid metabolism and PCa progression and suggests that measuring levels of medium- and long-chain acylcarnitines in pre-operative patient plasma may provide a basis for improving patient stratification.
Ramsay-Hunt syndrome and subsequent sensory neuropathy as potential immune-related adverse events of nivolumab: a case report
Authors: Sakoh Takashi , Kanzaki Mami , Miyamoto Atsushi , Mochizuki Sayaka , Kakumoto Toshiyuki , Sato Kenichiro , Uesaka Yoshikazu , Kishi Kazuma 
Published: December 2019

Abstract
Background
Nivolumab is an immune checkpoint inhibitor (ICI) and is used for the treatment of advanced non-small cell lung cancer (NSCLC). Several immune-mediated neurological adverse events associated with ICIs have been reported to date, such as Guillain-Barré syndrome. Nivolumab-associated neurological adverse events can vary, and their etiology remains unclear.

Case presentation
A 72-year-old man with NSCLC was treated with nivolumab as a second-line therapy. After 13 rounds of nivolumab therapy, he presented with Ramsay-Hunt syndrome (RHS) followed by acute ataxic sensory neuropathy. Antiviral therapy for Varicella-Zoster virus and prednisolone resulted in partial improvement of RHS, while almost no recovery was observed in the sensory neuropathy. However, the sensory ataxia significantly improved after intravenous immunoglobulin (IVIg) therapy, and interestingly, the facial palsy associated with RHS also improved. The neurological manifestations, nerve conduction study result, and imaging findings supported that dorsal root ganglia were the primary lesion site of acute ataxic sensory neuropathy.

Conclusions
Our case presented with the comorbidity of RHS and subsequent ataxic sensory neuropathy after nivolumab therapy to whom IVIg was effective. Our case suggested the wide variability of possible neurological symptoms, and the potential usefulness of IVIg to sensory ataxic neuropathy, seen in cancer patients with ICI treatment.
Neonatal body composition: crossectional study in healthy term singletons in Germany
Authors: Wiechers Cornelia , Kirchhof Sara , Balles Lena , Avelina Vanessa , Weber Romy , Maas Christoph , Pauluschke-Fröhlich Jan , Hallschmid Manfred , Preißl Hubert , Fritsche Andreas , Poets Christian F. , Franz Axel R. 
Published: December 2019

AbstractBackgroundDuring pregnancy, a variety of factors can influence fetal growth and development. Intrauterine growth may impact on later life and health. Neonatal body composition may be a more sensitive marker for the intrauterine environment than established anthropometric parameters at birth.MethodsTo study neonatal body composition determined by air displacement plethysmography in healthy, term singletons as national reference data, and to establish factors impacting on neonatal body composition in this population. This prospective cross-sectional observational study included 271 healthy, full-term, singletons born between June 2014 and July 2015. Body composition was measured within 96 h of birth using air displacement plethysmography.ResultsMedian (Q1, Q2) fat mass / total body mass (BF%) in German singletons was 10.8% (7.7–13.4) and fat free mass (FFM) 2843 g (2606–3099). Female infants had significantly increased BF% compared to male infants (11.2% (8.7–14.0) vs. 9.6% (7.2–12.1)). On multiple regression analysis, BF% and fat mass increased with female gender, maternal pre-pregnancy body mass index, non-smoking mother and parity, whereas FFM increased with male gender and increasing gestational age at birth. Gestational weight gain category, birth mode, and postnatal age at measurement were not associated with BF%, FFM or fat mass.ConclusionsWe generated BF% and FFM centiles for healthy, term, singletons born in Germany; these are similar to those found in other European countries. Infant body composition at birth was associated with modifiable (pre-pregnancy body mass index, smoking), and given factors (gender, gestational age at birth, parity).
Neonatal body composition by air displacement plethysmography in healthy term singletons: a systematic review
Authors: Wiechers Cornelia , Kirchhof Sara , Maas Christoph , Poets Christian F. , Franz Axel R. 
Published: December 2019

Abstract
Background
There is increasing evidence that intrauterine environment and, consequently, growth in utero have both immediate and far-reaching consequences for health. Neonatal body composition might be a more sensitive marker of intrauterine environment and neonatal adiposity than birth weight and could serve as a predictor for non-communicable diseases later in life.

Methods
To perform a systematic literature review on neonatal body composition determined by air displacement plethysmography in healthy infants. The systematic review was performed using the search terms “air displacement plethysmography”, “infant” and “newborn” in Pubmed. Data are displayed as mean (Standard deviation).

Results
Fourteen studies (including n = 6231 infants) using air displacement plethysmography fulfilled inclusion criteria for meta-analysis. In these, weighted mean body fat percentage was 10.0 (4.1) % and weighted mean fat free mass was 2883 (356) g in healthy term infants. Female infants had a higher body fat percentage (11.1 (4.1) % vs. 9.6 (4.0) %) and lower fat free mass (2827 (316) g vs. 2979 (344) g). In the Caucasian subpopulation (n = 2202 infants) mean body fat percentage was 10.8 (4.1), whereas data for reference values of other ethnic groups are still sparse.

Conclusions
Body composition varies depending on gender and ethnicity. These aggregated data may serve as reference for body composition in healthy, term, singletons at least for the Caucasian subpopulation.
Difficult differentiation of a somatic symptom disorder from anterior cutaneous nerve entrapment syndrome (ACNES): a case report
Authors: Yokoyama Narifumi , Shiraki Ryousuke , Watanabe Takashi , Shiinoki Makiko , Nin Michihiro , Shimizu Taro , Yasui-Furukori Norio , Shimoda Kazutaka 
Published: December 2019

Abstract
Background
Somatization is regarded as psychological or emotional distress in the form of physical symptoms that are otherwise medically unexplained.

Case presentation
We report a case of a patient with a somatic symptom disorder (SSD) and depression who was later diagnosed with anterior cutaneous nerve entrapment syndrome (ACNES) when Carnett’s test was positive and block anesthesia using trigger point injections dramatically improved the symptom of abdominal pain.

Conclusion
We concluded that the differentiation of SSDs, such as psychogenic pain, from ACNES is very difficult. Psychiatrists should be aware of this syndrome.
A simple method for in vitro preparation of natural killer cells from cord blood
Authors: Mu Yong Xu , Zhao Yu Xia , Li Bing Yao , Bao Hong Jing , Jiang Hui , Qi Xiao Lei , Bai Li Yun , Wang Yun Hong , Ma Zhi Jie , Wu Xiao Yun 
Published: December 2019

Abstract
Background
Cord Blood (CB) has been considered a promising source of natural killer (NK) cells for cellular immunotherapy. However, it is difficult to expand the large numbers of highly pure NK cells from CB without cell sorting and feeder cells/multiple cytokines. In this study, we try to develop a simple, safe and economical method for ex vivo expansion and purification of NK cells from CB without cell sorting and feeder cells/multiple cytokines.

Results
The large numbers (mean: 1.59 × 1010) of highly pure (≥90%) NK cells from CB could be obtained through interleukin-2, group A streptococcus and zoledronate stimulation of mononuclear cells using the 21-day culture approach. When compared to resting NK cells, expanded NK cells were a higher expression of activating receptors CD16, NKG2D, NKp30, NKp44, NKp46 and activating markers CD62L and CD69, while the inhibitory receptors, CD158a and CD158b remained largely unchanged. In addition, these cells showed a higher concentration of IFN-γ, TNF-α and GM-CSF secretion and cytotoxicity to K562 cells and acute myeloid leukemia targets than resting NK cells.

Conclusion
We develop a simple, safe and economical method to obtain high yield, purity, and functionality NK cells from CB without cell sorting and feeder cells/multiple cytokines.
Association of major dietary patterns and different metabolic phenotypes: a population-based study of northwestern Iran
Authors: Nikniaz Leila , Abbasalizad Farhangi Mahdieh , Tabrizi Jafar Sadegh , Nikniaz Zeinab 
Published: December 2019

Abstract
Background
Finding the relationship between the major dietary patterns and cardiometabolic phenotypes could be used for planning prevention programs based on the cultural and dietary habits to prevent transient from a metabolically healthy state to an unhealthy state. So, we aimed to assess the association between dietary patterns and cardiometabolic phenotypes in the northwestern population of Iran.

Method
In the present cross-sectional and population-based study, 504 adults sampled by cluster sampling in East-Azerbaijan, Iran. Factor analysis was used for determining the dietary pattern. Metabolic phenotypes were determined according to body mass index (BMI) cut–off point (25 kg/m2), and the presence of the metabolic syndrome. The independent sample t-test, one-way ANOVA, chi-square, and multinomial regression were used for statistical analysis.

Results
In both adjusted (OR: 2.24, 95% CI: 1.17, 4.31) and unadjusted models (OR: 3.14, 95% CI: 1.54, 5.42), the last tertile of the animal dietary pattern was associated with metabolically healthy obese (MHO) phenotypes. After adjusting, the last tertile of the animal dietary pattern was significantly associated with an increase of metabolically unhealthy obese (MUHO) phenotype (OR: 2.61, 95% CI: 1.18, 5.76).

Conclusion
In the present study, the animal dietary pattern was associated with MHO and MUHO phenotypes. It is suggested that some measures should be taken to strengthen nutrition education for the population and advocate a balanced diet to improve the condition.