bluuebunny/crossref_metadata_2025 huggingface dataset:
WITHDRAWN: Production and characterization of new composite materials from glass fiber, calcite, and starch reinforced WPET by extruder system
Authors: DENİZ Şermin , AYDOĞMUŞ Ercan , KAR Filiz
Published: April 2023

Various products are used as reinforcement elements to improve the properties of polymeric materials and to reduce costs. This study aimed to enhance the mechanical properties of waste polyethylene terephthalate (WPET). Besides, the contribution to environmental protection by using recycled products is one of the objectives of this study. Composite materials have been prepared by adding various ratios of glass fiber (3 wt.%, 6 wt.%, 9 wt.%, and 15 wt.%), calcium carbonate (5 wt.%, 15 wt.%, and 25 wt.%), and corn starch (3 wt.%) as filler into WPET. Morphological, thermal, mechanical, physical, and chemical properties of these composites have been examined by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), mechanical strength, and Shore D hardness tests. When the amount of starch in the samples is fixed, it has been observed that the hardness increases as the amount of calcite and glass wool increases. Although there is a slight decrease in thermal conductivity as the ratio of glass fiber increases, there is no significant change. However, as calcium carbonate (CaCO3) ratio increases, the thermal conductivity values also raise.
Bird and Arthropods Predation in Mosaic Agricultural Landscapes: Implication of Habitat Heterogeneity for Ecosystem Services
Authors: Osie Mulatu , Shibru Simon , Nemomissa Sileshi
Published: April 2023

Although predation is one of the key factors in determining the abundance and composition of predators, quantitative estimates of it in tropical rain forests remain patchy. We conducted an experiment in Kafa coffee agroecosystem, Southwestern Ethiopia to measure the predation rate of biocontrol on pest mimics and to assess the effect of habitat heterogeneity on these processes. We compared rates of attacks of birds and arthropods on 3000 plasticine caterpillars deployed in complex and tree simplified landscapes. We recorded a total of 33.9% incidences of predations; out of which, 46.90% was bird predation, 51.53% were gnawed by arthropods and 1.57% were unidentified. Predation rates of these natural enemies significantly differed (p < 0.05)among the landscapes. Nearly Twenty percent being in the complex and 14.2% in the tree simplified landscapes. Data were analyzed using a generalized linear mixed effect models of R program. We found higher predation rate of birds in the complex and more arthropods predation in tree simplified landscapes. We conclude that predation rates were positively related to the diversity of natural enemies and structurally complex natural habitats maintained a higher density of predators to control pests.
Development of mesoporous oxide structure using non–ionic surfactants for adsorptive application
Authors: Sarma Paran , Singh Sohan , De Mahuya
Published: April 2023

This study investigated the effect of non–ionic surfactants in developing structure of an oxide during preparation by precipitation. Aluminum oxide was used as base oxide while Tween 20 was used as the non-ionic surfactant. Effects of surfactant concentration and structure, pH and aging temperature on oxide properties were investigated. The use of surfactant modified the structure of aluminium oxide increasing fraction of mesopores as well as surface area and pore volume at all concentrations of surfactant. However, variation of surface area with surfactant concentration was not significant. Bayerite was observed as the predominant phase in all samples. Alkaline pH was observed to facilitate enhanced interaction between surfactant and hydroxide matrix resulting in high average pore size. The surface area of the samples did not differ significantly but pore volume increased from 0.6 to 1.1 ml/g as aging temperature was increased. More uniform and narrower mesopore distribution were observed for oxide prepared in presence of Tween 20 compared to that prepared using Tween 60 or Tween 80, suggesting higher interaction with the former. The 30 wt.% zinc supported on surfactant modified aluminium oxide showed higher thiophene removal capacity compared to when unmodified support was used.
Analysis of non-uniform laminar flow past a circular cylinder on the flow and sound field evolution using direct numerical simulation approach
Authors: Kumar Nilesh , Kumar Shashi , Arumuru Venugopal , Bhumkar Yogesh G.
Published: April 2023

This paper analyses the effects of a non-uniform laminar flow past a circular cylinder using the direct numerical simulation (DNS) approach. Compared to the cylinder immersed in a uniform flow case, modifications caused by the non-uniform approaching flow on the evolution of the flow and sound fields are studied in detail in the present work. The prescribed non-uniform velocity profile at the inlet has a Gaussian distribution and imitates a jet or a wake flow velocity profile. The sound is generated due to periodic vortex shedding behind the circular cylinder. The frequency of vortex shedding and the strength of the shed vortices depend on the inflow velocity profile. Hence variation of the inflow velocity profile alters the shed vortices, changing the generated sound field. It is observed that the amount of gain or deficit present in the prescribed inflow velocity profile compared to the uniform inflow profile alters the sound field information. The jet kind of inflow profile creates a sound of higher frequency and intensity in contrast to the wake kind of inflow profile. The presence of shear in the inflow velocity profile is also expected to change the sound propagation direction. However, in present simulations, the distance over which sound propagation is considered is small compared to the wavelength of the sound waves, and sound beam drift effects are not observed much.
Biennial sugar beets capable of flowering without vernalization treatment
Authors: Yosuke Kuroda , Kuranouchi Toshikazu , Okazaki Kazuyuki , Takahashi Hiroyuki , Taguchi Kazunori
Published: April 2023

A biennial sugar beet (Beta vulgaris) generally takes two years to flower and complete its life cycle. In the first year, the plant grows vegetatively, and then enters a period of cold winter. In the second year, it grows reproductively and initiates flowering under long daylength conditions. Among biennial beets that grow vegetatively in outdoor field conditions, two strains were found to flower early under 24-hour daylength conditions without being exposed to cold temperatures. The hypothetical locus related to the flowering trend was named ‘BLOND’ and crossings between strains of the BLOND and normal biennials yielded hybrid derivatives of F1, F2, and BC1F1. Bolting rate was investigated both in an outdoor field under natural daylength conditions and in a greenhouse with an artificial 24-hour daylength. BLOND strains and hybrid derivatives did not bolt in the outdoor field similar to those in the biennial control strains. This enables evaluation of important agronomic traits, such as yield, which cannot be evaluated using an annual control strain in which all plants bolt. However, under 24-hour daylength conditions, BLOND strains bolted without vernalization treatment, unlike those in the biennial control strains but similar to annuals. The bolting rates of the hybrid derivatives suggested that the flowering characteristics of BLOND were mainly controlled by a single dominant gene. Because seed production in BLOND is estimated to take at least four months, similar to that of the annual beet, BLOND’s bolt rate may be applicable for speed breeding of sugar beets.
A mild dose of aspirin promotes hippocampal neurogenesis and working memory in experimental ageing mice
Authors: Andrews Jemi Feiona Vergil , Selvaraj Divya Bharathi , Kumar Akshay , Roshan Syed Aasish , Anusuyadevi Muthuswamy , Kandasamy Mahesh
Published: April 2023

Aspirin treatment is the most widely used preventive measure against cardiovascular diseases. Aspirin is also expected to provide beneficial effects on the brain. However, the association between aspirin treatment and neurocognitive functions is a subject of debate. Ample reports strongly advocate that a mild dose of aspirin positively modulates hippocampal plasticity responsible for memory. Aspirin is a selective cyclooxygenase (COX)-2 inhibitor but the underlying mechanism through which aspirin modulates neuroplasticity remains unclear. Adult neurogenesis in the hippocampus has been established as an underlying basis of learning and memory. Therefore, aspirin treatment might be linked to the regulation of hippocampal neurogenesis. Thus, this study revisited the effect of low-dose aspirin on learning and memory in correlation with the regulation of hippocampal neurogenesis in the brains of ageing experimental mice. Results from the novel object recognition (NOR) test, Morris water maze (MWM), and cued radial arm maze (cued RAM) revealed that aspirin treatment enhances working memory in experimental ageing mice. Further, the co-immunohistochemical assessments on the brain sections indicated an increased number of doublecortin (DCX) positive immature neurons and bromodeoxyuridine (BrdU)/neuronal nuclei (NeuN) double-positive newly generated neurons in the hippocampi of mice in aspirin-treated group compared to the control group. Recently, enhanced activity of acetylcholinesterase (AChE) in circulation has been identified as an indicative biomarker of dementia. The biochemical assessment in the blood of aspirin-treated mice showed decreased activity of AChE than that of the control group. This study supports the procognitive effects of aspirin which can be translated to treat dementia.
The prognostic value of coronary flow reserve in patients with non- obstructive coronary artery disease and microvascular dysfunction A systematic review and meta-analysis with focus on imaging modality and sex difference
Authors: Jensen Signe Miang , Prescott Eva Irene Bossano , Abdulla Jawdat
Published: April 2023

Pupose: To clarify prognosis of patients with non-obstructive coronary artery disease (NOCAD) and coronary microvascular disease (CMD) assessed as low coronary flow reserve (CFR) according to imaging modalities and sex difference.
Methods: Comprehensive systematic literature review and meta-analyses were conducted. Risk of death and major adverse cardiac events (MACE) were pooled and compared in patients with abnormally low versus normal CFR using cut-off limits 2.0-2.5. Random effects model used for estimation of odds ratios (OR) and hazard ratios (HR) with 95% confidence interval (CI).
Results: Nineteen eligible observational studies provided data for death and MACE, publication bias was insignificant, p=0.62. Risk of death and MACE were significantly higher in patients with low (n=4.612, 29%) than normal CFR (n=11.367, 71%): using transthoracal echocardiography (TTE) (OR 4.25 (95%CI: 2.94, 6.15) p<0.001) and (OR 6.98 (95% CI:2.56, 19.01) p<0.001), positron emission tomography (PET) (OR 2.51 (CI 95%: 1.40, 4..49) p=0.002) and (OR 2.87 (95%CI: 2.16, 3.81) p<0.001), and invasive intracoronary assessment (OR 2.23 (95%CI: 1.15, 4.34) p<0.018), and (OR 4.61 (95%CI: 2.51, 8.48) p<0.001), respectively. Pooled adjusted HR for death and MACE were (HR 2.45(95%CI: 1.37, 3.53) p<0.001) and (HR 2.08 (95%CI: 1.54, 2.63) p<0.001) respectively. Studies comparing men and women with abnormally low CFR demonstrated similar worse prognosis in both sexes.
Conclusion: Low CFR is associated with poorer prognosis in patients with NOCAD regardless of sex. TTE may overestimate risk of death and MACE, while PET seems to be more appropriate. Future studies are needed to consolidate the current evidence.
Slow gait speed could be a signal for common geriatric syndromes besides sarcopenia
Authors: He Xu , Li Yan , Chen Jun , Zhang Li , Quan Jing , Lu Sunrui , Ying Zhou , Huang Yan , Wang Kehua
Published: April 2023

Background In China geriatricians is inadequate for the growing elderly. We need more doctors to recognize geriatric syndromes with a simple examination, which could help more elderly have better care.Aims Clarified that slow gait speed could be a signal to identify common geriatric syndromes besides sarcopenia in elderly outpatients.Methods According to the gait speed cut-off (< 1.0m/s), we classified 985 elderly outpatients (457 men and 528 women) into two groups. The groups were defined as the normal speed group (NSG, gait speed ≥ 1.0m/s), and the slow speed group (SSG, gait speed < 1.0m/s). We used the CGA management system Simply Edition (CGA-SE) software to collect data and compared demographic variations and the prevalence of functional decline in the two groups.Results Participants in SSG were significantly older, shorter in height, lighter in weight, used more drugs, and had a higher score in Edmonton, SDS, SAS, and MNA, and a lower score in BADL, and MMSE than in NSG. And they had significantly higher prevalence percentages in frailty, disability, depression, and dementia than in NSG. In addition, gait speed was an independent protective factor associated with frailty, disability, dementia, and swallowing dysfunction. And slow gait speed was an independent risk factor associated with frailty, depression, and dementia. Furthermore, participants with comorbidity, better function in daily life, and good cognition usually had faster gait speeds. However, participants with polypharmacy, low education, malnutrition risk, and frailty usually had slow gait speed(p < 0.05).Discuss Clinical physicians should give more attention to those with slow gait speed elderly outpatients, and be alert to their geriatric syndromes.Conclusions Slow gait speed could be a signal for several common geriatric syndromes in elderly outpatients. We recommended 6 meters gait speed test as a routine examination for the elderly, not only in the geriatric department but also others serving the elderly.
Development and Validation of a Diagnostic Model for AFP- Negative Hepatocellular Carcinoma
Authors: Yu Zhou , Chen Dongmei , Zheng Yansong , Wang Xuedan , Huang Shuna , Lin Tiansheng , Lin Yihan , Zhang Yanfang , Huang Yingna , Ou Qishui , Huang Jinlan
Published: April 2023

Purpose：AFP appears to be negative about 30% of overall hepatocellular carcinoma (HCC). Our study aimed to develop a nomogram model to diagnose AFP negative HCC (AFPN-HCC).
Patients and methods: The training set and the external validation set consisted of 516 and 456 objects. LASSO, univariate and multivariable logistic regression were performed to construct the model and then transformed into a visualized nomogram. We further used the receiver operating characteristic (ROC) curves, the calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC) for validation.
Results:Four variables included age, PIVKA-II, platelet (PLT) counts and prothrombin time(PT) were selected to establish the nomogram. The area under the curve (AUC) of the ROC to distinguish AFPN-HCC patients was 0.937(95%CI, 0.892-0.938) in training set and 0.942(95%CI, 0.921-0.963) using the validation set and indicated satisfactory discriminative ability of the model. The calibration plots showed favorable consistency between the prediction of the nomogram and actual observations. DCA and CIC showed that the nomogram was clinically useful.
Conclusions:Our model was effective for discrimination of AFPN-HCC from control subsets, and might be helpful for the diagnosis for AFPN-HCC.
Lactate-Modulated the Immunosuppressive Function of Myeloid-Derived Suppressor Cells through TET2-mediated SGK1 demethylation
Authors: Chu Ying , Shen Hua , Dai Haiyan , Wang Yahui , Da Wenxin , Dai Yao , Chen Zhihong , Shen Bo , Zhang Yan , Bao Pengtao , Zhang Xinxin , Cao Fenghua , Zhu Wei , Xu Huaxi , Wang Shengjun , Ma Jie
Published: April 2023

Myeloid-derived suppressor cells (MDSCs) is a collection of myeloid-derived heterogenetic cells, which has immunosuppressive capabilities in the occurrence and development of tumor. We found that compared with spleen-derived MDSCs (SP-MDSCs) of lung cancer mice xenograft model, tumor -derived MDSCs (T-MDSCs) had stronger immunosuppressive function which was caused by lactate in the tumor microenvironment. Here we revealed that lactate was involved in regulating the function and glycolysis of MDSCsand serum and glucocorticoid-inducible kinase 1(SGK1) should be an important factor during this process. Further studies demonstrated that lactate could down-regulate the DNA methylation level of SGK1 by regulating the Ten-Eleven-Translocation-2 (TET2). In summary, our findings indicated an indispensable role of lactate in the immunosuppressive functions and glycolysis of MDSCs for the first time and offer an effective therapeutic target for anti-tumor therapy.
Bosons Thermodynamics in the gravity field
Authors: Ferrari Loris , Pavan Fabrizio
Published: April 2023

A uniform force like the weight has been shown to forbid Bose-Einstein condensation (BEC), due to the discretness of the Airy spectrum, resulting from the weight. We show that BEC is forbidden even if the Airy spectrum is treated as continuous, in what we call the approximate continuous limit (ACL). The absence of BEC is due to the non vanishing limit g (ε0) > 0 of the Riemann integrable density of states (DOS), at the ground state level ε0. A thorough study is made, showing the way the Bose-Einstein condensate grows, at temperatures lower than the fictiuos BEC temperature Tf , resulting from the limit ε0 → 0. A comparison with some experimental data shows the difference between the confinement in a rigid-wall reservoir and in a harmonic trap.
Perceptions and Intention to get vaccinated against Mpox among the LGTBIQ+ Community during the 2022 outbreak: A Cross-Sectional Study in Peru
Authors: Araoz-Salinas Julieta M. , Ortiz-Saavedra Brando , Ponce-Rosas Linda , Soriano-Moreno David R. , Soriano Anderson N. , Alave Jorge , Gonzales-Zamora Jose A.
Published: April 2023

Introduction: Vaccination against mpox can control the outbreak by targeting high-risk groups, such as the LGTBIQ + community. The aim of the study was to evaluate the perception and intention to get vaccinated against mpox among the LGTBIQ + community in Peru.Methods We conducted a cross-sectional study from November 1, 2022, to January 17, 2023, in Peru. We included individuals over 18 years old, belonging to the LGBTIQ + community, and residing in the departments of Lima and Callao. To evaluate the factors associated with the intention to be vaccinated, we used Poisson regression with robust variance to create a multivariate model.Results The study comprised 373 individuals who self-identified as members of the LGBTIQ + community. The participants had a mean age of 31 years (SD ± 9), with 85.0% of males, and 75.3% reporting to be homosexual men. The majority (88.5%) expressed their intention to receive the vaccine against mpox. Believing that the vaccine is safe was associated with a higher intention to be vaccinated (aPR: 1.24; 95% CI: 1.02 to 1.50; p = 0.028).Conclusions Our study population showed a high level of mpox vaccination intent. Educational campaigns reinforcing the concept of vaccine safety should be conducted to increase the intention and possibly the vaccination rate in the LGTBIQ + community.
Ramanujan τ-function and its relationship with PSL(2,ℤ) for ℒ24(τ)+,E
Authors: Bhattacharjee Deep , Bose Pradipta Narayan , Samal Priyanka
Published: April 2023

A relation has been computed for the Θ- function and τ- function with the modular group PSL(2,ℤ) for the Leech Lattice ℒ equipped 24D Euclidean Space denoted as E in the positive–definite with even form + for the coherent structure ℒ24(τ)+,E.
The unique turret region of Kv3 channels governs the mechanism of action of highly specific positive allosteric modulators.
Authors: Covarrubias Manuel , Liang Qiansheng , Zhi Lianteng , Cirqueira Leonardo , Pilati Nadia , Marasco Agostino , Gunthorpe Martin , Alvaro Giuseppe , Large Charles , Treptow Werner
Published: April 2023

Small-molecule modulators of diverse voltage-gated K+ (Kv) channels may help treat severe neurological disorders. However, the development of selective modulators requires an understanding of their mechanism-of-action (MoA). We applied an orthogonal approach to elucidate the MoA of an imidazolidinedione derivative (AUT5), which is a highly specific positive allosteric modulator (PAM) of Kv3.1 and Kv3.2 channels. AUT5 modulation involves positive cooperativity and preferential stabilization of the open state. Critically, we found that the unique and highly conserved extracellular turret region of Kv3.1 and Kv3.2 essentially governs AUT5 modulation. Furthermore, leveraging on the cryo-EM structure of Kv3.1a, atomistic blind docking calculations revealed four equivalent AUT5 binding sites near the turrets and between the voltage-sensing and pore domains of the channel’s tetrameric assembly. Therefore, the unique Kv3 turret emerges as a novel structural correlate of the selective MoA of a new class of Kv3 channel PAMs with a therapeutic potential.
Haemophagocytic lymphocytosis (HLH) vicious cycle in a Cannabinoids addict patient case report and disease review.
Authors: Amer Amro Essam , Hamdar Hiba , Amer Ahmed Essam , Mohamed Shueb A. , Abdelrahman Pensee Chebl Abdelgwaad , Megid Nermen Magdy Abdel , Frrag Eman M.
Published: April 2023

Haemophagocytic lymphocytosis (HLH) is a rare life-threatening syndrome caused by the uncontrolled activity of cytokines, natural killers, and macrophages, which can alter the activity of the organism, resulting in multiple organ dysfunction and mortality. Fever, splenomegaly, coagulopathies, dyspnea, changes in mental status, or irritability may be associated with HLH diseases. Depending on the underlying causes, such as bacterial or viral infections, HLH may be primary, hereditary, or secondary. The early diagnosis and treatment of patients are directly related to their prognosis and clinical outcome. On the other hand, HLH can present a number of obstacles, particularly for children and newborns, as well as hematological defects which might cause other autoimmune disorders. Case presentation: We present a case of a 28-year-old male patient admitted to the hospital with a history of persistent high grade fever for two weeks, right lower limb swelling three weeks prior to admission, and right side weakness for one month. Aside from being addicted to cannabis for three years, the patient has no prior medical history. On admission, the patient was awake, conscious, oriented, and hemodynamically stable. A complete blood count, ultrasound examinations, and a whole-body CT scan revealed that the results were favorable for multiple enlarged lymph nodes and hepatosplenomegaly. The patient was given acyclovir, Vfend, Colistin, Targocid, Tinam, Septrin, and anticoagulant during the follow-up. The patient's clinical condition was rapidly deteriorating; a bone marrow biopsy was performed, which revealed haemophagocytosis; and dexamethasone was started. The patient's clinical condition deteriorated during his hospital stay until he went into cardiac arrest and had to be resuscitated for 30 minutes with pulseless electrical activity. Background and Aim: This case suggests that we should be vigilant to the patient who is admitted to the hospital with symptoms for unknown reasons, in order to diagnose HLH as soon as possible and clarify its cause, and it also puts several theories regarding the pathogenicity of this disease in our hands, which will be described in this case, making this case a subject for discussion and research in the medical field. Conclusion: Haemophagocytic lymphocytosis (HLH) is a severe inflammatory disease that improperly controls the body's immune response. Viruses and bacterial infections are just two examples of the various etiological causes that can cause it. Lab results and symptom presentations that are particular to the primary infection can indicate it. Diagnosis and treatment must be provided as soon as possible in order to reduce morbidity and mortality.
CCAR Stress Testing Impacts on Home Equity Loan Originations and Purchases
Authors: Sedai Akash , Medda Francesca
Published: April 2023

This study shows how post-crisis stress tests have affected the
supply of home equity business loans. Stress tested banks reduce their loan
originations but the reduction in loan purchases is more dramatic among
stress tested banks that failed the exercise. The magnitude of these effects
is inversely proportional to the size of the loans. Even though the aggregate
level of credit supply is relatively unchanged, within each size category of
loans adopted in this study, growth rates are directly proportional to its
origination size. The loan distributions significantly differ among stresstested
and non-stress-tested banks and there are significant geographical
shifts in loan originations both by categories of banks and size of loans.
Regulatory Science: Mathematical vs. Statistical Models
Authors: Shepard Richard B
Published: April 2023

Natural resource companies do not object to environmental regulations that are consistent and support predictability. Consistency and predictability are critical for decision making under conditions of uncertainty. Natural ecosystems are inherently variable across a broad range of temporal and spatial scales; climate change, drought, and societal desires for sustainability make people more aware of this variability. The science used for development and enforcement of environmental regulations has not kept pace with developments in ecological theory and the analytical tools capable of describing, characterizing, classifying, and predicting natural ecosystems as well as distinguishing natural variability from anthropogenic changes.Because natural resource industries (agriculture, energy, mining) provide the base for all economic and societal activities it is critical that environmental statutes and regulations be regularly updated to use the most technically sound and legally defensible scientific knowledge and tools.Mathematical models were the tools of choice when environmental statutes and regulations were introduced, perhaps because they were successfully applied to static components of the built environment such as buildings and bridges. While their limitations for highly variable natural ecosystems were accepted then, there is now no benefit to not replacing them with statistical models.This paper describes limitations in policy and regulatory decision-making based on mathematical models and explains how the appropriate statistical models avoid the subjectivity and rigidity of the former. Changing the basis of determining and justifying policy and environmental regulations is consistent with the concepts of regulatory science applied to human health.https://doi.org/10.21423/jrs-v04n04p010 (DOI assigned 5/14/2019)
Regulation of Pharmaceuticals in Developing Nations: A Case from Nepal
Authors: Poudel Bhupendra Kumar , Ishii Itsuko
Published: April 2023

Department of Drug Administration (DDA), medicine regulatory authority of Nepal, is aligned towards achieving Universal Health Coverage through the regulation of medicines, pharmacies, manufacturing facilities and medicine testing laboratories from its offices located in Kathmandu, Birgunj, Biratnagar and Nepalgunj and takes legal or administrative actions as appropriate.  It has its own regulatory laboratory, National Medicines Laboratory for testing and analysis of medicines. Besides, DDA reports suspected ADR to Upshala Monitoring Centre, Sweden, provides drug information and conducts regulatory trainings. Unlike in the developed world, DDA may not be able to fulfill all of its objectives. But then, a mechanism of regulation of pharmaceuticals is functional and is dynamic as per national need.https://doi.org/10.21423/jrs-v04n04p018 (DOI assigned 5/14/2019)
Reduction of False Positives in the Chili Candy Analysis Method for Filth Using a Newly Developed Correction Factor
Authors: Loechelt-Yoshioka Hans K. , Senff Wynn A.
Published: April 2023

In the examination of chili candy for filth using the current method and mathematical formula, it was observed that product samples containing small amounts of filth elements were disproportionally violative. After examining numerous regulatory samples, there was clear indication that it would be necessary to re-evaluate the mathematical formula to reduce false positive results. The original formula calculation is based entirely on the dry weight of recovered chili powder in the product. The formula failed to take into account the loss of soluble material from the chili powder at two critical phases: during candy production, and during processing for filth analysis. This paper provides a means to account for the lost soluble material from the chili powder and adds a correction factor to the original formula to address the high rate of false positive results.https://doi.org/10.21423/jrs-v05n01p029 (DOI assigned 4/17/2019)
Effective Use of Foreign Clinical Data in Approvals for Medical Devices in Japan
Authors: Shirotani Mari , Chiba Koji
Published: April 2023

Initial clinical development of medical devices occurs mainly in the USA and EU, with many medical devices registered in Japan afterwards. As the clinical performance of medical devices is less sensitive to ethnicity than the efficacy and safety of a drug, the performance of such devices can often be evaluated using foreign clinical data. The factors affecting the requirement for Japanese clinical data was investigated in the Japanese approvals of 103 high-risk devices, occurring between April 2005 and March 2015. The requirement for Japanese clinical data was associated with no approval in the USA and EU and the absence of foreign clinical data in the submission (p<0.001). Our results suggest that Japanese clinical data are not an essential requirement when foreign clinical data are included in the Japanese data package for approval, although, for 50% of devices with approval in the USA or EU, Japanese clinical data were still required for the Japanese approval. Reasons for this included the possibility that the performance of the device was sensitive to ethnicity associated with the medical environment, and that the device had been updated from the original one.https://doi.org/10.21423/jrs-v05n01p035 (DOI assigned 4/17/2019)
Autheniticity, Adulteration, and Counterfeit in Food, Drugs, and Dietary Supplements
Authors: Molins Ricardo
Published: April 2023

It is necessary and urgent to provide the analytical technical support to regulations aimed at curving fraud in food, pharmaceutical, and dietary supplements, to protect public health and allow fair trade.https://doi.org/10.21423/jrs-v05n01pi (DOI assigned 4/17/2019)
Establishing Laboratory Analysis Procedure for EPA FIFRA Enforcement Samples to Meet the ISO/IEC 17025:2005 Requirements using Flexible Scope Approach
Authors: Johnson Yoko Shibuya , Horvath Gareth
Published: April 2023

An ISO/IEC 17025:2005 accredited laboratory procedure that quantifies analytes and validates an analytical method used simultaneously was established for analyzing pesticide misuse samples. Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the U.S. Environmental Protection Agency (EPA) grants the authority over regulating pesticide use to each state. Samples for pesticide misuse cases such as drift complaints are analyzed by state laboratories (state FIFRA labs). State FIFRA labs receive samples that require quick turnaround with a variety of unique matrix/analyte combinations. The majority of the samples are analyzed by non-standard methods that are developed by the laboratory. It is impractical to pre-validate such non-standard methods. Yet, the forensic nature of pesticide misuse investigation samples demands legally defensible analytical data. The author's laboratory developed an expedited validation procedure that is conducted simultaneously with analyte quantitation by using the standard addition technique. The procedure received ISO/IEC 17025:2005 accreditation from the American Association for Laboratory Accreditation under their Flexible Scope Policy. The developed validation protocol and associated procedural changes made to the daily operations are supported by several laboratory documents that are unique to the Flexible Scope option.https://doi.org/10.21423/jrs-v05n02p010 (DOI assigned 3/11/2019)
Elimination of Sodium Chloride Interference on Heavy Metal Analysis in High-Salt Food
Authors: Xiao Yabing , He Jian , Ma Xing , Zhang Haibin , Li Wei
Published: April 2023

A simple method using Chelex-100 chelating resin and Atomic Absorbance Spectroscopy determination of lead, cadmium and copper in high-salt food was established. This method could solve the problem of interference on the determination of lead and cadmium in salt matrix. Kd values of sodium (Na), lead (Pb), cadmium (Cd) and copper (Cu) on chelating resin was measured. The influence of pH values of solution on absorption and behavior of ions on resin were investigated. Elution curve for Na and Cd was demonstrated. Absorption capacities of resin to Pb/Cd/Cu/Na were determined. The developed method was applied for analysis of high-salt samples. The recoveries were in the range of 91.6%~98.6% with relative standard deviations (RSDs) in the range of 2.0%～6.7%.https://doi.org/10.21423/jrs-v05n02p029 (DOI assigned 3/11/2019)
Fertilizer Mixer Performance Evaluation using Chloride Titration
Authors: Hsieh Yi-Cheng , Herrman Timothy
Published: April 2023

Mixing processes are a critical step in manufacturing blended fertilizer products. Although each stage of the production process is monitored to prevent deficiencies and ensure quality in fertilizer production, evaluation of mixing performance by regulatory agencies are the keys to assessing quality of the final product. The Office of the Texas State Chemist (OTSC) conducted a fertilizer mixer evaluation study, which involved two main components: sample collection and lab analyses. Samples from 9 mixers were collected from 7 fertilizer manufacturing locations in Texas. Firms were selected based on the type of fertilizer components currently in use and the type of mixer(s), which included cement type, vertical, volumetric and paddle. Sample collection follows the process outlined by The Fertilizer Institute (TFI). Samples are collected from the blended product and from the individual raw ingredient materials. In the laboratory, the samples from the individual raw materials and blended product stream cut samples were analyzed for size guide number (SGN), density, particle number, and nitrogen (N)-phosphorous (P)-potassium (K) levels, and Chloride (Cl-) content. The sample accuracy was calculated by comparing the actual formula weights to the expected values for the blended product. To determine mixer efficiency and reproducibility, coefficient of variations were calculated to determine the variability between various samples of the blended product. Our results indicated Cl- titration is a cost effective method to efficiently evaluate mixer performance, the mixing time of tested cement mixer may result in high variation in the N-P-K analysis, and Cl- level in blended samples. Based on our previous feed mixer study, facilities operating these cement mixers may consider to check mixer readiness and increase mixing time to achieve better homogeneity.https://doi.org/10.21423/jrs-v06n02p008 (DOI assigned 1/24/2019)
Is the total review time of new medical devices related to the size of the company?: Medical devices development and its related factors in Japan
Authors: Tomotsugu Naoki , Kaneko Masayuki , Takayama Akane , Narukawa Mamoru
Published: April 2023

Japan has one of the largest medical device markets in the world, but most devices used in Japan are pioneered by foreign medical device companies. On the other hand, medical device companies in Japan have significant potential to develop innovative medical devices. Through this research, we aim to elucidate the factors related to the total review time of new medical devices so that innovative medical devices would be developed sooner. Using the lists of approved medical devices disclosed by the Pharmaceuticals and Medical Devices Agency (PMDA), we chose all the new medical devices that were approved in Japan between Fiscal Year (FY) 2009 and 2015. We conducted two main types of analyses based on the total review time after submission and sales of the companies. The total review time tends to decrease with "Year of approval by the PMDA'' in FY 2009 to 2015 (p < 0.001). Moreover, the total review time of small and medium-sized companies is greater than that of large companies (p = 0.004). In conclusion, the total review time of new medical devices in Japan appears to be related to the following two factors: (1) year of approval, and (2) size of the enterprise.https://doi.org/10.21423/jrs-v06n02p024 (DOI assigned 1/24/2019)
The Journal of Regulatory Science in Continuous Publication
Authors: Molins Ricardo
Published: April 2023

Beginning in November 2018, the Journal of Regulatory Science (JRS) will adopt the “Continuous Publication” modality.https://doi.org/10.21423/jrs-v06n02pi (DOI assigned 1/24/2019)
Comparison of Southern-by-Sequencing (SbSTM) technology and Southern Blot Analysis for Molecular Characterization of Genetically Modified Crops
Authors: Brink Kent , Anitha S. C. , Beatty Mary K. , Anderson Jennifer A. , Lyon Megan , Weaver Janine , Dietrich Nina
Published: April 2023

Southern blot analysis is typically used for molecular characterization of genetically modified (GM) crops.  Southern-by-Sequencing (SbSTM technology, hereafter referred to as SbS) is a high-throughput, sequence-based alternative technique utilizing targeted sequence capture coupled with next-generation sequencing (NGS) and bioinformatics tools to achieve the same molecular endpoints.  To demonstrate that both SbS and Southern blot analysis reach the same conclusions about insertion copy number and intactness of the inserted DNA, both techniques were used to characterize four soybean GM events containing simple or complex DNA insertions.  To demonstrate that both techniques reach the same conclusions about the presence of unintended DNA, maize GM events containing Agrobacterium plasmid backbone fragments were characterized.  Additionally, oligonucleotides containing varying lengths of target sequence were analyzed to compare both techniques’ sensitivity for detecting small insertions.  SbS and Southern blots had similar sensitivity and provided comparable results for copy number and intactness of simple and complex DNA insertions.  Both techniques also had comparable results for detection of unintended plasmid backbone DNA sequences and small DNA fragments.  Thus, SbS can deliver the same endpoints as Southern blot analysis for key molecular characterization aspects of GM crops and gene edited varieties, providing important information to inform regulatory decisions.

https://doi.org/10.21423/jrs-v07brink
Best Practices for the Use of Portable X-Ray Fluorescence Analyzers to Screen for Toxic Elements in FDA-Regulated Products
Authors: Palmer Peter T. , Jacobs Richard M. , Yee Sally , Li Tao , Reed Christopher , Nebenzahl Deborah , Liu Anita , Chu Gordon , MacCorkell Elizabeth , Duong Tracey , Sawyer Travell , Douglas Michele
Published: April 2023

Globalization of trade has made it easy for consumers to purchase products from all over the world. A small fraction of these products contain toxic elements that may pose a health risk to consumers, and there is a clear need for small, portable, and fast methods to rapidly screen these products. Portable X-Ray Fluorescence (XRF) analyzers are the ideal tool for this application, as they involve minimal sample preparation and analysis times of a minute or less. XRF is also well suited for elemental analysis of products that are resistant to traditional hydrochloric/nitric acid digestions such as cosmetics and dietary supplements, and can prevent contamination of expensive Inductively Coupled Plasma Mass Spectrometry (ICP-MS) instruments used for ultra-trace level analyses. Moreover, XRF can be used to monitor most of the elements in the periodic table, with detection limits as low as 1-10 ppm for some elements. This article describes an U.S. Food and Drug Administration (FDA) field study to screen for consumer products containing toxic elements at an International Mail Facility (IMF). After brief training and hands-on activities using real-world samples, two three-person teams using two portable XRF systems analyzed 183 different products over a seven-hour time period, and found 10 that contained significant levels of mercury (Hg), lead (Pb), arsenic (As), and/or selenium (Se), potentially in violation of FDA’s requirements. The goal of this article is to provide guidelines and recommendations for safe, reliable, and efficient use of XRF to screen for toxic elements in FDA-regulated products.
Recommendations for Maximum Incorporation Rates of Whole Food in 90-Day Rat Feeding Studies
Authors: Goodwin Laurie , Glenn Kevin , Petrick Jay , Ranjan Rakesh , Roper Jason , Sauve-Ciencewicki Alaina , Bauman Patricia , Hodge-Bell Kimberly , Lipscomb Elizabeth
Published: April 2023

More than 25 years of 90-day rat feeding studies with GM crops have consistently shown that these studies provide no additional value to safety assessments in the absence of a testable hypothesis. However, some regulatory authorities continue to require these studies while also specifying that the test material should be relevant to the product to be consumed and tested at the maximum incorporation rate not causing nutritional imbalance. In the absence of known or suspected adverse effects, dose range-finding studies are not feasible, yet scientifically justified incorporation rates are needed to balance the nutritional requirements of the animals and to achieve the goal of observing adverse effects, should they occur. When 90-day rat feeding studies are required for GM crop safety assessments, the following maximum incorporation rates (w/w), are recommended: 50 percent maize, 30 percent soybean, 60 percent rice, 15 percent canola, and 10 percent cottonseed. These recommendations are based on empirical data regarding maximum exposure to test material and avoidance of nutritional imbalances and/or exposure to anti-nutrients or toxins naturally present in the whole food. Each recommended maximum incorporation rate provides test material consumption at levels substantially higher than the highest human worldwide chronic consumption and is fully sufficient to address regulatory requirements.
https://doi.org/10.21423/jrs-v09i2goodwin
Socio-Economic Considerations and Potential Implications for Gene-Edited Crops
Authors: Ludlow Karinne , Smyth Stuart , Falck-Zepeda Jose
Published: April 2023

Regulatory clarity and efficiency are increasingly important for the successful commercialization of technologies resulting from public and private R&D investments. This article examines recent developments in the movement away from mostly science-based risk assessment regulatory and variety approval systems focusing on human and animal health and environmental safety to hybrid systems that include assessment of socio-economic considerations allowed for under the auspices of the Cartagena Protocol on Biosafety. We propose that socio-economic consideration assessments can be grouped into three methodological categories: empirically based, legally grounded and consensus approaches. Our exploration of developments in the three categories reveals gaps in data, consistency and methodology rigor, that must be addressed for efficient and reliable socio-economic consideration assessment. We assess the potential impacts of these gaps on the regulation of gene-edited crop varieties, concluding that if gene-edited crops are regulated as genetically modified crops, they will endure the same fate, that is, lengthy regulatory approval processes and failure to be commercialized. The end result being that the regulatory burdens in potential adopting and food insecure countries will prevent important new crop varieties from reaching farmers and producers for their use.
https://doi.org/10.21423/jrs-v09i2ludlow
Utility of Weight-of-Evidence Components in Risk Assessment: Example of Digestion Results in the Allergenicity Assessment of Newly Expressed Proteins in Genetically Engineered Crops
Authors: Herman Rod , Roper Jason , Storer Nicholas
Published: April 2023

Various weight-of-evidence risk-assessment frameworks have been used for regulatory decision making. In this policy commentary, we critically assess the value of including gastric and/or intestinal digestion results in the weight of evidence designed to inform the allergenicity assessment of newly expressed proteins in genetically engineered crops. This example highlights a general concept: specifically, that there is negligible value in considering a factor as a component of the risk assessment when differing outcomes for this factor do not result in different risk decisions under any reasonable hypothetical scenario regarding results from the other components of the risk assessment. We conclude that equitable and science-based regulatory guidance should include examples of weight-of-evidence scenarios illustrating how differing outcomes for each individual component within the weight of evidence would result in a different conclusion on the acceptability of the potential risk under consideration. Critically assessing each component of the weight of evidence in this manner helps avoid inclusion of components that can only distract risk assessors from the critical decision-making process, possibly resulting in inconsistent risk assessment outcomes for the same datasets.
https://doi.org/10.21423/jrs-v09i2rod
Measure of Value: FDA in the Age of COVID
Authors: Beninger Paul
Published: April 2023

The US Food and Drug Administration (FDA) is the institutional regulatory gateway through which healthcare business sectors gain access to commercial markets in pharmaceuticals, biologicals, vaccines, medical devices, diagnostic test kits and persona protective equipment. The unfolding of events for the COVID-19 pandemic serve as a case study for understanding, in real time, how FDA has contributed value to the healthcare sector.
Federal regulatory agencies, such as FDA, require strong processes to provide fair and consistent outcomes to retain the trust of the stakeholder community. These processes include statutes and regulations, internal manual of standard operating procedures and policies, guidance documents, external advisory committees and the Office of Inspector General. These processes cover the following activities: product development conditions, regulatory pathways, types of approvals, manufacturing quality, and post marketing safety. Together, the institutional experiences that led to and shaped these processes prepared FDA for the challenges associated with COVID-19.
The sum of twelve decades of experience comes down to the following goals that provide value to the degree with which each is successful: 1) The manufacturing process must meet standards of quality and be secured. 2) Medical products must be shown, through scientific evidence and based on evidentiary standards, to be safe and effective for human use. 3) Identified risks must be mitigated, by labeling at a minimum, with additional strategies as necessary. 4) Provisions must exist for extraordinary circumstances of limited unmet medical needs and of threats to public health and national security.
https://doi.org/10.21423/jrs-v10i1beninger
Introduction to a Special Issue on Regulatory Applications of Portable Tools and Methods to Monitor Toxic Substances in Consumer Products
Authors: Palmer Pete
Published: April 2023

No abstract