bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distributions associated with simultaneous multiple hypothesis testing
Authors: Yu Chang , Zelterman Daniel 
Published: October 2020

AbstractWe develop the distribution for the number of hypotheses found to be statistically significant using the rule from Simes (Biometrika 73: 751–754, 1986) for controlling the family-wise error rate (FWER). We find the distribution of the number of statistically significantp-values under the null hypothesis and show this follows a normal distribution under the alternative. We propose a parametric distributionΨI(·) to model the marginal distribution ofp-values sampled from a mixture of null uniform and non-uniform distributions under different alternative hypotheses. TheΨIdistribution is useful when there are many different alternative hypotheses and these are not individually well understood. We fitΨIto data from three cancer studies and use it to illustrate the distribution of the number of notable hypotheses observed in these examples. We model dependence in sampledp-values using a latent variable. These methods can be combined to illustrate a power analysis in planning a larger study on the basis of a smaller pilot experiment.
Glycine mitigates fertilizer requirements of agricultural crops: case study with cucumber as a high fertilizer demanding crop
Authors: Zargar Shooshtari Fateme , Souri Mohammad Kazem , Hasandokht Mohammad Reza , Jari Sepideh Kalateh 
Published: October 2020

Abstract
Background
Different approaches have been used to improve mineral nutrient status of plants in absence of chemical fertilization and toward safer products and improved human health. Amino acids have been proposed with such roles in different recent studies. In this study, glycine was applied as foliar (250, 500 and 1000 ppm) or as soil (250 and 500 mg/plant) to cucumber plants compared to unfertilized control and NPK fertilization, under greenhouse conditions.

Results
The results showed that all glycine treatments increased leaf area and the economic life of plants compared to control. Soil application of glycine at higher concentration of 500 mg/plant was able to produce the same or better records than NPK fertilization, particularly regarding leaf mineral concentration, plant economic life and total yield. Leaf macro- micro-nutrients were most increased under 500 mg soil-glycine application. Foliar spray of 500 ppm glycine resulted in better records than the other two levels, as spray of 1000 ppm glycine showed adverse and toxic effects including leaf necrosis. Fruit firmness was increased only by NPK and soil application of 500 mg glycine, whereas fruit vitamin C was increased by NPK fertilization, soil application of glycine at both levels (250, 500 mg) and foliar application of glycine at 500 ppm compared to control plants.

Conclusion
The results indicate that soil application of 500 mg glycine/plant was able to improve leaf mineral and physiological characteristics towards higher yield and quality.
Using the Glasgow Benefit Inventory questionnaire to quantify the health benefits of lymphoedema treatment in patients with head and neck cancer
Authors: Halliday Edwin , Gittins Jayne , Ahsan Syed Farhan 
Published: October 2020

Abstract
Background
Lymphoedema is a common side effect after treatment for head and neck cancer. Our treatment protocol involves staging the degree of lymphoedema and then offering treatment comprising skin care, manual lymphatic drainage, simple lymphatic drainage, compression and elastic therapeutic tape. The Glasgow Benefit Inventory is a validated post-interventional questionnaire applicable to otorhinolaryngology interventions which measures changes in health status. The aim of this study was to quantify the health benefits of lymphoedema treatment using the Glasgow Inventory Benefit questionnaire, in patients with a history of treated head and neck cancer.

Methods
Any patient who had undergone treatment with curative intent of a primary head and neck malignancy who had been referred for lymphoedema treatment within a 6 month period was eligible for inclusion. Patients completed a questionnaire after finishing the course of lymphoedema treatment.

Results
A total of 15 patients completed the questionnaire. Ten patients (67%) demonstrated some level of improvement in quality of life, while two (13%) reported no benefit and three (20%) reported negative improvements. The average score for the total Glasgow Benefit Inventory scale was + 7.2. The greatest benefit was demonstrated with the physical benefit subscale (+ 13.1). The average general benefit score was + 9.0.

Conclusions
Lymphoedema treatment involves techniques which can fairly easily be taught to patients to complete at home. In this study, there were mild improvements in patient reported quality of life using the Glasgow Benefit Inventory in the majority of patients. Clinical interest has increased in lymphoedema recently, but there is still limited information about the effectiveness of treatments and future research should look to address these issues.
Health Outcomes at 1 Year After Thermal Ablation for Cervical Precancer Among Human Papillomavirus– and Visual Inspection With Acetic Acid–Positive Women in Honduras
Authors: Slavkovsky Rose C. , Bansil Pooja , Sandoval Manuel A. , Figueroa Jacqueline , Rodriguez Doris M. , Lobo Jose Saul , Jeronimo Jose A. , de Sanjosé Silvia 
Published: October 2020

PURPOSE This study aims to assess the detection of cervical intraepithelial lesions grades 2 and 3 (CIN2-3) at 1 year after treatment with thermal ablation among human papillomavirus (HPV)–positive and visual inspection with acetic acid (VIA)–positive women. METHODS All women screened and triaged for cervical cancer at four government health facilities in Honduras who were eligible for ablative treatment were enrolled and treated with thermal ablation. Women with confirmed CIN2-3 and a subset of women with CIN1/normal diagnoses at baseline were evaluated at 12 months. Follow-up procedures included HPV testing ( careHPV), VIA, directed biopsy (if VIA-positive), and Papanicolaou test (if HPV positive, VIA negative). Outcomes at 1 year included histologic or cytologic assessment of CIN lesions among those with any abnormal test. RESULTS Among the 319 women treated with thermal ablation, baseline histologic diagnoses were available for 317. Two (0.6%) had invasive cancer, 36 (11.4%) had CIN3, 40 (12.6%) had CIN2, and 239 (75.4%) had CIN1/normal histology. Among the 127 women eligible for follow-up, 118 (92.9%) completed all study procedures at 1 year. Overall, 98 (83.1%) had no evidence of CIN2-3 or persistent low-grade infection, 13 (11.2%) had CIN1/atypical squamous cells of undetermined significance, six (5.1%) had CIN2/high-grade squamous intraepithelial lesion, and 1 (0.8%) had a persistent CIN3. No adverse events associated with thermal ablation at 1 year were registered. CONCLUSION A high proportion of women had no evidence of CIN2-3 at 1 year after thermal ablation treatment. Thermal ablation is an alternative to cryotherapy that may facilitate greater treatment coverage and prevent unnecessary deaths from cervical cancer.
Cell-to-Medium Concentration Ratio Overshoot in the Uptake of Statins by Human Hepatocytes in Suspension, but Not in Monolayer: Kinetic Analysis Suggesting a Partial Loss of Functional OATP1Bs
Authors: Lee Wooin , Koyama Satoshi , Morita Kiyoe , Kiriake Aya , Kikuchi Ryota , Chu Xiaoyan , Lee Nora , Scialis Renato J. , Shen Hong , Kimoto Emi , Tremaine Larry , Ishiguro Naoki , Lotz Ralf , Maeda Kazuya , Kusuhara Hiroyuki , Sugiyama Yuichi 
Published: October 2020

AbstractSuspended human hepatocytes (SHH) have long been used in assessing hepatic drug uptake, while plated human hepatocytes in short-term monolayer culture (PHH) have gained use in recent years. This study aimed to cross-evaluate SHH and PHH in measuring the hepatic uptake mediated by organic anion transporting polypeptide 1Bs (OATP1Bs). We compared the time courses of cell-to-medium (C/M) concentration ratios and initial uptake clearance values of the OATP1B substrates (pitavastatin, rosuvastatin, cerivastatin, pravastatin, dehydropravastatin, and SC-62807) between SHH and PHH. For all compounds except cerivastatin, the C/M ratios in SHH displayed an apparent overshoot (an initial increase followed by a decrease) during the 180-min uptake experiment, but not in PHH. Based on the literature evidence suggesting the possible internalization of OATP1Bs in primary hepatocytes, separate experiments measured the drug uptake after varying lengths of pre-incubation in the drug-free medium. The initial uptake clearances of pitavastatin and rosuvastatin declined in SHH beyond an apparent threshold time of 20-min drug-free pre-incubation, but not in PHH. Kinetic modeling quantitatively captured the decline in the active uptake clearance in SHH, and more than half of the active uptake clearances of pitavastatin and rosuvastatin were prone to loss during the 180-min uptake experiment. These results suggested a partial, time-delayed loss of the functional OATP1Bs in SHH upon prolonged incubation. Our results indicate that PHH is more appropriate for experiments where a prolonged incubation is required, such as estimation of unbound hepatocyte-to-medium concentration ratio (Kp,uu) at the steady-state.
Androgen Suppresses In Vivo and In Vitro LH Pulse Secretion and Neural Kiss1 and Tac2 Gene Expression in Female Mice
Authors: Esparza Lourdes A , Terasaka Tomohiro , Lawson Mark A , Kauffman Alexander S 
Published: October 2020

Abstract
Androgens can affect the reproductive axis of both sexes. In healthy women, as in men, elevated exogenous androgens decrease gonad function and lower gonadotropin levels; such circumstances occur with anabolic steroid abuse or in transgender men (genetic XX individuals) taking androgen supplements. The neuroendocrine mechanisms by which endogenous or exogenous androgens regulate gonadotropin release, including aspects of pulsatile luteinizing hormone (LH) secretion, remain unknown. Because animal models are valuable for interrogating neural and pituitary mechanisms, we studied effects of androgens in the normal male physiological range on in vivo LH secretion parameters in female mice and in vitro LH secretion patterns from isolated female pituitaries. We also assessed androgen effects on hypothalamic and gonadotrope gene expression in female mice, which may contribute to altered LH secretion profiles. We used a nonaromatizable androgen, dihydrotestosterone (DHT), to isolate effects occurring specifically via androgen receptor (AR) signaling. Compared with control females, DHT-treated females exhibited markedly reduced in vivo LH pulsatility, with decreases in pulse frequency, amplitude, peak, and basal LH levels. Correlating with reduced LH pulsatility, DHT-treated females also exhibited suppressed arcuate nucleus Kiss1 and Tac2 expression. Separate from these neural effects, we determined in vitro that the female pituitary is directly inhibited by AR signaling, resulting in lower basal LH levels and reduced LH secretory responses to gonadotropin-releasing hormone pulses, along with lower gonadotropin gene expression. Thus, in normal adult females, male levels of androgen acting via AR can strongly inhibit the reproductive axis at both the neural and pituitary levels.
Mitochondrial survivin reduces oxidative phosphorylation in cancer cells by inhibiting mitophagy
Authors: Townley Amelia R. , Wheatley Sally P. 
Published: October 2020

ABSTRACT
Survivin (also known as BIRC5) is a cancer-associated protein that is pivotal for cellular life and death – it is an essential mitotic protein and an inhibitor of apoptosis. In cancer cells, a small pool of survivin localises to the mitochondria, the function of which remains to be elucidated. Here, we report that mitochondrial survivin inhibits the selective form of autophagy called ‘mitophagy’, causing an accumulation of respiratory-defective mitochondria. Mechanistically, the data reveal that survivin prevents recruitment of the E3-ubiquitin ligase Parkin to mitochondria and their subsequent recognition by the autophagosome. The data also demonstrate that cells in which mitophagy has been blocked by survivin expression have an increased dependency on glycolysis. As these effects were found exclusively in cancer cells, they suggest that the primary act of mitochondrial survivin is to steer cells towards the implementation of the Warburg transition by inhibiting mitochondrial turnover, which enables them to adapt and survive.
This article has an associated First Person interview with the first author of the paper.
Efficient Transesterification of Methyl Acetate with 2-Propanol by the Selective Removal of Methanol Using Zeolite Membranes
Authors: Ikeda Ayumi , Hasegawa Yasuhisa 
Published: October 2020

Abstract
An FAU-type zeolite membrane was applied to the efficient transesterification of methyl acetate with 2-propanol. When the transesterification reaction was carried out using DOWEX 50W as a catalyst, the conversion of methyl acetate reached 38% at equilibrium. Removal of the by-produced methanol selectively from the equilibration solution using the FAU-type zeolite membrane increased the conversion of methyl acetate to 57% by shifting the chemical equilibrium. This suggests that methanol-selective membranes have the potential to promote efficient transesterification reactions.
Diagnostic accuracy of a urine dipstick for detecting albuminuria in hypertensive patients
Authors: Panta Phornwipa , Techakehakij Win 
Published: October 2020

Background: Screening for albuminuria is generally recommended among patients with hypertension. While the urine dipstick is commonly used for screening urine albumin, there is little evidence about its diagnostic accuracy among these patients. This study aimed to assess the diagnostic accuracy of a dipstick in Thai hypertensive patients for detecting albuminuria. Methods: This study collected the data of 3,067 hypertensive patients, with the results of urine dipstick and urine albumin-to-creatinine ratio (ACR) from random single spot urine being examined in the same day at least once, at Lampang Hospital, Thailand, during 2018. For ACR, a reference standard of ≥ 30 mg/g was applied to indicate the presence of albuminuria. Results: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value of the trace result from dipsticks were 53.6%, 94.5%, 86.5%, and 75.5%, respectively. The area under the receiver operating characteristic curve of the dipstick was 0.748. Conclusion: Using the dipstick for screening albuminuria among hypertensive patients should not be recommended due to its low sensitivity. In response to high PPV, a trace threshold of the dipstick may be used to indicate presence of albuminuria.
Post-COVID recovery: characteristics of chronically critically ill patients admitted to a long-term acute care hospital
Authors: Hassenpflug Meg Stearn , Jun Dale , Nelson David R. , Dolinay Tamas 
Published: October 2020

Background: Survivors of COVID-19 pneumonia often suffer from chronic critical illness (CCI) and require long-term hospitalization. Long-term acute care (LTAC) hospitals are vital in the care of CCI patients, but their role for patients post COVID-19 infection is not known. Barlow Respiratory Hospital (BRH) is a 105-bed, LTAC hospital network serving ventilator-dependent and medically-complex patients transferred from the ICUs of hospitals in southern California. We report patient characteristics of our first series of COVID-19 survivors admitted to the post-acute venue of an LTAC hospital. Methods: Single-center observational descriptive report of patients recovering from acute infectious complications of COVID-19 pneumonia requiring long-term respiratory support. Results: From 28 April to 7 September 2020, 41 patients were admitted to BRH for continued recovery from COVID-19 pneumonia. The length of stay at the transferring hospital was twice that of non-COVID patients admitted during the same time period. Median age: 68 [44-94] years, 61% male, 80.5% with tracheostomy, 51.2% on invasive mechanical ventilation, 22% receiving hemodialysis. All mechanical ventilation and hemodialysis interventions were initiated at the transferring hospital. Conclusions: To our knowledge, this is the first report to characterize CCI and medically complex COVID-19 patients transferred to the post-acute venue of an LTAC hospital. Patients on average spent over six weeks in the transferring hospital mostly in the ICU, are largely elderly, carry the known risk factors for COVID-19 infection, and experienced respiratory failure necessitating prolonged mechanical ventilation via tracheostomy. Our findings suggest that these patients will continue to require considerable medical interventions and treatments, including weaning from mechanical ventilation, owing to the numerous sequelae of the infection and the burden of acute-on-chronic diseases. As ICU survival rates improve, this research further emphasizes the important role of the LTAC hospital in responding to the COVID-19 crisis.
Neglected Fracture in Maxillofacial: Case Series
Authors: Khairiza Rizka , Setyarto Muhammad Rizqy 
Published: October 2020

Introduction: Neglected fracture is a condition of fracture that is not handled or mishandled, resulting in a state of delay in treatment, or a worse condition and even a disability. The technical difficulty was associated with a greater incidence of complications and often lead to a suboptimal result. A more precise understanding of maxillofacial fracture's demographic patterns will help healthcare providers manage maxillofacial injuries.
Method: Twenty-nine patients with neglected maxillofacial fractures were registered in the Division of Plastic Reconstructive and Aesthetic Surgery, Dr. Kariadi Central-General Hospital Semarang, January 2015 to December 2018. The collected information included gender, age, etiology, and site of fracture. Some of the cases are presented.
Result: Neglected fracture of maxillofacial occurred predominantly in young adults. The male population was more frequently affected (62%)—most patients with neglected maxillofacial fractures associated with MVA (84%). The Mandible was the most common site of the fracture, followed by ZMC.
Conclusion: The possibility of a fracture of Mandible and ZMC or adjacent bones should be considered in any facial trauma, especially related to MVA injury. Early and proper management will provide a better result.
Randomized Trial of 2 Delayed-Release Formulations of Linaclotide in Patients With Irritable Bowel Syndrome With Constipation
Authors: Chey William D. , Sayuk Gregory S. , Bartolini Wilmin , Reasner David S. , Fox Susan M. , Bochenek Wieslaw , Boinpally Ramesh , Shea Elizabeth , Tripp Kenneth , Borgstein Niels 
Published: October 2020

INTRODUCTION:
Immediate-release (IR) formulation of linaclotide 290 μg improves abdominal pain and constipation (APC) in patients with irritable bowel syndrome (IBS) with constipation. Delayed-release (DR) formulations were developed on the premise that targeting the ileum (delayed-release formulation 1 [DR1]) or ileocecal junction and cecum (MD-7246, formerly DR2) would modulate linaclotide's secretory effects while preserving pain relief effects.

METHODS:
This phase 2b study randomized patients with IBS with constipation to placebo or 1 of 7 once-daily linaclotide doses (DR1 30, 100, or 300 μg; MD-7246 30, 100, or 300 μg; or IR 290 μg) for 12 weeks. Key efficacy endpoints were change from baseline in abdominal pain and complete spontaneous bowel movement frequency, and 6/12-week combined APC+1 responder rate.

RESULTS:
Overall, 532 patients were randomized; mean age was 45.1 years, and most were women (83.3%) and White (64.7%). All linaclotide DR1 and MD-7246 groups experienced greater improvements in abdominal pain from baseline and vs placebo throughout treatment. Linaclotide DR1 and IR led to numerically greater improvements from baseline in complete spontaneous bowel movement frequency and higher APC+1 responder rates compared with placebo; MD-7246 results were similar to placebo. Diarrhea was the most common adverse event with DR1 and IR; rates were similar between MD-7246 and placebo.

DISCUSSION:
Altering the site of drug delivery in the intestine might uncouple linaclotide's pain relief from secretory effects. Persistent, modest abdominal pain improvement with limited impact on bowel symptom parameters, as seen across MD-7246 doses, warrants further study of MD-7246 as a novel treatment for abdominal pain, regardless of IBS subtype.
Pensar en formas sonoro-simbólicas
Authors: Sad Levi Jorge 
Published: October 2020

En el presente artículo trataremos el problema de la significación de los fenómenos tímbricos en el marco de la semiología de Molino y Nattiez. Distinguimos el mero sonido en tanto vibración de las formas sonoro-simbólicas. Éstas últimas son el resultado de la acción intencional y exclusiva de un acto de producción/escucha y puede ser estudiada en su triple dimensión, en tanto hecho material, en tanto fenómeno perceptual y en tanto fenómeno imaginario. Las formas sonoro-simbólicas portan la signatura de cada operación de producción realizada por compositores, programadores de software, luthiers, diseñadores de sonido, productores discográficos y músicos.
Agriculture Supply Chain Management-An Operational Perspective
Authors: Bhatia Mahak , Bhat G.M.J. 
Published: October 2020

Goal: An integrated model for production and distribution of agricultural produce is developed. The objective of mathematical model formulated is to maximize farm revenues by investigating the production and logistics parameters associated with the type of crop cultivated. The paper aims to develop a mathematical & conceptual framework for crop distribution that will provide an optimal farm return with the reduction in farm cost.
Methodology: Mathematical and conceptual model is developed to overcome the challenges faced by growers of perishable crops. The decision of model is made on the basis of traditional/ previous season factors such as resource availability, market price of the produce in previous year. Linear Programming as a tool is used for formulation.
Results/Findings: The complexity of model depends on the type of crop cultivated and capital invested by the growers. The developed model thus results in, planning a farm model from cultivation till harvesting. The timing which is an important parameter in the case of perishable crops were taken under formulation.
Limitations of the Investigation: To analyze the different parameters affecting the decision variables a hypothetical farm planting tomatoes, cucumbers and bell peppers are taken under considered to determine the operational cost involved in logistics management of perishable crops. Only the perishable crops were considered to study so that the complexities and the constraints associated in packaging, storage and harvesting of these crops will be observed and analyzed. Most of these farm model often overviews the factor such as product deterioration, product life span, freshness & quality, price dynamics, transportation and inventory costs.
Practical Implications: The study supports the farmers practising perishable crops, to maximize the farm revenue and minimize the farm losses. The developed model will help the growers of perishable produce to analyze the scenario and consider the crop according to the market demands and available farm resources.
Originality / Value: None of the studies conducted so far will simultaneously focus on minimization of product loss and maximization of farm revenues.