bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Rubber Effluent and NPK Fertilizer on the Performance and Fruit Quality of Snake Tomato (Trichosanthes cucumerina L. Haines) in a Three and Four Years Old (An Existing) Rubber Plantation
Authors: Uwumarongie A. M. D. , Emuedo O. A. , Uzunuigbe E. O. , Ohikhena F. U. , Chukwuka A. N. , Ugiagbe-Ekue U. , Omoruyi J. I. , Omorogbe J. A. , Aghedo S. O. , Musa S. O.
Published: September 2022

Small holder rubber farmer that account for over 75% of rubber production in Nigeria has withdrawn from production as a result of income gap created by the long gestation period of rubber amidst other agronomic challenges, hence the need to create an agronomic system that will incorporate other compactable short duration to generate additional and early source of income and take care of other agronomic challenges. An experiment was conducted in 2018 and 2019 cropping seasons to evaluate the influence of rubber effluent and NPK fertilizer on the performance and fruit quality of snake tomato in a three and four year old (an existing) rubber plantation. The treatments include sole rubber, sole snake tomato and their intercrop combinations with rubber effluent and NPK laid out in randomized complete block design replicated thrice. Data were collected on vine length, vine girth, number of leaves, leaf area, fruit yield and its components, nutrient content and uptake. Growth parameters measured increased with increase in rubber effluent application however NPK fertilized plants were superior to rubber effluent treated plant at increased dosage as there was no marked difference between plants treated with effluent at 70kgN-1 rubber effluent and NPK treated plants, it was also observed that the fourth year plant were higher than the third year. Nutrient content was observed to increase with fertilizer application as non fertilized had the lowest nutrient content, the least uptake was observed in the non fertilized plants.
In vitro and In vivo Control of Fungal Cobweb Disease of Pleurotus ostreatus (Jacq), Using Organic Materials
Authors: Nmom F. W. , Nrior R. R. , Jumbo F. S.
Published: September 2022

Aim: Assessment of In vitro and In vivo Control of Fungal Cobweb Disease of Pleurotus ostreatus (Jacq), using organic materials.

Study Design: This study was designed to control the disease by using plant materials as organic control agent; both In vitro and in vivo.

Methodology: In Pleurotus ostreatus. In the In vitro test; food poison method was used while the in vivo test was undertaken by inoculation of fully colonized substrate bags of Pleurotus ostreatus infected with cobweb disease with crude extracts of Piper guineense and lime juice as treatment stock.

Results: The results indicated P. guineense inhibition of the growth of the pathogen at 22mm while lime juice did not show any impact on the growth of the pathogen. Additionally, P. guineense inhibited the growth of the pathogen in fully colonized but infected substrates bags of P. ostreatus invivo; such that the treated samples grew and developed the fruiting bodies of the mushroom, 3 days after treatment; whereas the one treated with lime juice developed the cobweb disease.

Conclusion: The study showed that effectiveness of P. guineense extract on the pathogen was possibly due to the bioactive chemicals such as phenols, tannins, flavonoid etc which concentration in the plant material occurred in surplus. These may have interfered with the molecular targets of the pathogen and caused it to loose cellular integrity and leakage of cell content. Alternatively, the study revealed that lime juice was ineffective; possibly because of the solvent used for it's preparation which could not enhance the release of the essential bioactive chemicals in lime juice for anti fungals. Consequently, this study recommends the use of P. guineense to mushroom farmers against fungal cobweb disease of oyster mushrooms.
A Virtual Laboratory Ecosystem in Medical Education: Effectiveness of Simulations Made by Instructor
Authors: Khorasani Fatemeh Shiran , Nour Ghazal Ghasemi , Pisheh Ali Farsi , Assadi Reza
Published: September 2022

Theory: The technological revolution has profoundly changed our lives. Learning has also been affected by the significant advances in technology, leading human society to a place where distance learning would become inevitable. One of the many tools facilitating distance learning is virtual laboratories that use simulations for educational purposes and turn theoretical knowledge into practical skills. Virtual laboratories can break down the barriers of time and place for skill acquisition among learners. They offer access to laboratories or clinical equipment at a lower cost.

Hypotheses: This study aimed to set up a digital ecosystem (VirtuLab) where instructors can create customized interactive simulators for medical students. We hypothesized that VirtuLab can motivate students and help them improve technical skills through steps.

Methods: To compare the traditional teaching method (physical testing and working with real-life devices) and the virtual method (using a simulator), we initially created a graphic, virtual environment with the help of computer software and programming languages. We defined a simulated device that can help medical students (interns and externs) learn four different defibrillator applications (AED MODE, CARDIOVERSION, DC SHOCK, and PACEMAKER) virtually. After completing the virtual experiment, participants were invited to provide feedback for better performance. Then, using a questionnaire, users' opinions and scores were collected, and statistical comparisons were performed to determine the effectiveness of the virtual laboratory.

Results: Our findings showed that the time spent on each step, the total number of clicks, and the number of mistakes (failed clicks) had decreased significantly from the initial steps to the last one. The feedback obtained from the learners showed that VirtuLab has made the educational content understandable and tangible for 93% of them. Also, 87% of participants expressed their satisfaction with the simulator and found it motivating.

Conclusion: The times recorded by users during the steps indicated that with the help of a virtual simulator, learners' time and mistakes were significantly reduced through steps. With VirtuLab, it was possible to repeatedly learn and test different options without additional cost and improve practical skills in a series of steps. Besides, it was an appealing environment to up motivation, confidence, and effective learning in users.
Fecal Microbiota Transplant
Authors: Silva Mariana Araujo Mendes , Barud Mariana Dias Lopes , Barkett Gabriel Vieira , Almeida Maria Eduarda Gonçalves , Leão Mariella Vieira Pereira
Published: September 2022

Aims: The fecal microbiota transplantation (FMT) may be a possible solution for symptoms reduction and improvement of the clinical condition in Inflammatory bowel diseases (IBDs), such as Ulcerative Colitis (UC) and Crohn's Disease (CD). In addition to being effective in other conditions associated with disequilibrium in gastrointestinal microbiota, such as recurrent Clostridium difficile infection (RCDI) and Metabolic Syndrome (MS). The aim of this study was to review the applicability of FMT: in UC, CD, RCDI and MS.

Study Design: Minireview.

Place and Duration of Study: Faculty of Medical Sciences of São José dos Campos- Humanitas, between June 2021 and August 2022.

Methodology: A literature search was performed in the PubMed database for clinical trial studies and review articles, published in the last 10 (ten) years. The remission of clinical conditions was established as the primary outcome and exclusion criteria was not blind or incomplete blinding studies. Based on these studies, a review regarding the applications of FMT in patients with IBD, RCDI and MS, especially its therapeutic effects, was performed.

Results: In total, 53 (fifty-three) articles were selected. Studies have shown that FMT can be useful in the treatment of RCDI with cure rates ranging from 85% to 90% and represent a possible alternative to antibiotic therapy in cases of primary infection by C. difficile. FMT seems to be effective in inducing remission of UC, but its durability and long-term safety are still not well defined. Furthermore, in the treatment of Crohn's disease and metabolic syndrome, some studies show beneficial effects, but further studies are needed.

Conclusion: The studies are optimistic and, even if modest, suggest that FMT has the potential for treatment and/or remission of different inflammatory and infectious conditions.
Atypical Clinical Presentation of Childhood Osteosarcoma: Case Report
Authors: Ihuarula Eneh Chizoma , Franklin Nduka Ugochukwu
Published: September 2022

Aim: Highlight childhood Osteosarcoma as uncommon in a pre-adolescent female’s scapula.

Presentation of Case: 9-year-old female with left scapular outgrowth, weight loss, paleness  cachexia and axillary lymphadenopathy. Mass measured 27 by 53 cm, hard, tender with smooth, shiny unattached skin. Shoulder and Chest CT showed huge, well demarcated, heterogenous 14.6cm by 13.4cm by 14.4cm soft tissue mass with lobulated margins on the left scapular with its lytic destruction. Multiple nodules were seen on ipsi-lateral lung involving adjacent pleura. Malignant mesenchymal moderately pleomorphic cells with large pleomorphic hyperchromatic occasionally mitotic nuclei in a fibrous background with neoplastic lacy bone trabeculae, alternating hyper-cellular and hypo-cellular areas, dilated congested vessels were visualized on histology. Metastatic Osteosarcoma was diagnosed. Neo-adjuvant chemotherapy was given. Surgical tumor debulking awaited.

Discussion: The peak age for childhood Osteosarcoma is reported as 10–14years for females and 15–19 years in males which coincides with the adolescent growth spurt in both sexes (Tanner stage 3 or Sexual Maturation Rating (SMR) 3 in girls). Our pre-adolescent patient is noteworthy hence our documentation. In children Osteosarcoma occur primarily in the metaphyseal region of tubular long bones with 42% in the femur, 19% tibia and 10% humerus. Rarely in skull, pelvis or scapular (8%). The inflammatory features seen in osteosarcoma mimic osteomyelitis, cellulitis, trauma and benign bone tumors as strong differentials. Our patient’s late presentation features rather mimic our diagnosis. Our patient’s histology support Osteoblastic Osteosarcoma with high grade histology. A variant previously reported in sacrum, iliac crest and pubis. Late presentation seen has been cited as a major factor affecting surgical method as it will in this case. Otherwise limb salvage surgery with chemotherapy remains the management with best outcome.

Conclusion: Scapular Osteosarcoma in a pre-adolescent female is an uncommon presentation, hence this report.
Digital Microscopy using Online Mapping Technology: a Solution for Oral Pathology Education in Virtual Learning
Authors: Nour Ghazal Ghasemi , Ghazi Narges , Pisheh Ali Farsi , Assadi Reza , Asadi Elham
Published: September 2022

Objective: Our study aimed to develop a database containing high-quality digital oral and maxillofacial pathology (OMFP) slides without the high cost of whole slide imaging (WSI) for students and educators in low-income countries.

Methods and Materials: First, general expectations and criteria of the software were determined by asking the OMFP specialists and students during focus group meetings. Then, we generated a digital OMFP slides database available in different angles and magnifications. Next, with assistance from programmers, the offline software was linked to the database and piloted to evaluate the software faults. Users were also asked to assess the software and the evaluation continued until reaching the desired outcome. Finally, the updated version was presented to 27 dental students (third- and fourth-year) during their clinical pathology course. Students’ opinion toward the database was then evaluated using a standard questionnaire. Students’ scores were also compared to that of the last semester.

Results: Our findings showed that most students found the digital pathology software helpful, easy to use, reliable, well-organized, consistent, inclusive, and helpful. Overall, the participants regarded the experience as satisfactory. There was no significant difference between the students’ exam scores compared with the population average.

Conclusion: According to our results, digital pathology slides can improve oral pathology education and help dental students and professors in clinical and practical learning.
Kluver Bucy Syndrome: A Rare Neurological Disease with Several Challenges
Authors: Prajjwal Priyadarshi , Chaudhary Ansh , Ranjan Raunak , Chaudhary Bhupendra
Published: September 2022

Kluver Bucy Syndrome is an extremely rare disorder with a diverse presentation that can be confused with certain common diseases such as Korsakoff’s psychosis, Pick’s disease, and Alzheimer’s dementia. The most common risk factors overall and in children include Herpes simplex encephalitis. In adults, temporal lobe stroke subsequent to several possible etiologies is the second most common cause. Almost any condition that affects the brain (majorly the temporal lobe) can lead to Kluver Bucy Syndrome, making it more difficult to find out the underlying cause. The syndrome is named after Paul Bucy and Heinrich Kluver who discovered it in the monkeys. The various manifestations occur because of the involvement of the amygdala and hippocampus in the temporal lobe and include amnesia which may be anterograde or retrograde, hyperphagia, hyperorality, hypersexuality, visual agnosia, and hypermetamorphosis. The limbic system may get affected causing the above manifestations too. Management of the Kluver Bucy Syndrome is challenging and needs more research as pharmacotherapy and behavioural therapies are the only known interventions to treat patients with KBS currently with not so good outcomes as the delay in the diagnosis makes it not respond to the medications quite a number of times. The diagnosis is mainly clinical and early detection and management of the underlying cause could help provide a good prognosis. In this Review article, we review the conditions leading to Kluver Bucy syndrome, its pathophysiology, clinical features, and the major challenges in its diagnosis.
Ophthalmic Uses of Atropine: A Review
Authors: Eze Ugochukwu A. , Nathaniel Godswill I. , Pepple Godswill
Published: September 2022

Atropine has been used in medical practice for decades and is one of the essential emergency drugs. Its applications in ophthalmology have also followed a long trajectory. Therefore, this review is intended to explore the various uses of Atropine in ophthalmology. Atropine uses in strict ophthalmic indications have extensive diagnostic and therapeutic outlay including Examination under anesthesia, cycloplegic refraction, myopia, and amblyopic management, post trabeculectomy management, synechiae treatment, floppy iris syndrome, and uveitis management. The side effects have been shown to be dose-dependent with no long-term sequelae. Atropine has remained an important medicine in ophthalmic practice globally.
To Evaluate Preliminary Pharmacological Screening of Plant Extract of Ficus auriculata Lour for Anti - ulcer Activity
Authors: Joshi Deepak Chandra , Joshi Nirmal , Harshita . , Kumar Tirath
Published: September 2022

Objectives: To Evaluate Preliminary Pharmacological screening of plant extract of Ficus Auriculata Lour for  Anti - Ulcer activity.

Materials and Methods: The fresh leaves of plant ficus auriculata lour werecollected from the wild forest area of village Mushyoli Distt. Bageshwar (Uttarakhand), India. The identification and authentication of the plant leaf’s of ficusauriculta lour (BSI/NRC/Tech./Herb.(Ident.)/2019-20/433) was done byDr S.K.Singh Research officer Botany (Scientist E) at Botanical Survey of India, (Northern regional centre, Dehradun).

Results: The results of the pyloric ligation model showed that one or more processes were responsible for the reduction in baseline gastric output, the inhibition of ulcers index, the rise in stomach capacity, and the elevation in pH of gastric fluid.  The consumption of alcoholic beverages has been shown to significantly increase the levels of reduced glutathione (GSH), while the consumption of the leaves of the Ficus auriculata tree has been shown to significantly reduce the damage to the gastric mucosa caused by the consumption of alcoholic beverages.

Conclusion: There was a greater reduction in the severity of ulcers in patients who took the ethanolic extract of Ficus auriculata. Treatment with an ethanolic extract of Ficus lour leaves at dosages of 200 and 400mg/kg body weight exhibited statistically significant anti-ulcer action (p 0.0001) on the percent protection against the formation of ulcers in models produced by indomethacin. It displays a lowered stomach ulcer index, decreased total gastric acidity, increased total gastric volume, and increased total gastric protein, in contrast to the disease control. Additionally, it demonstrates an enhanced gastric pH. All of these data point to the possibility that the high flavonoid content is responsible for some of its anti-ulcer actions.
Studies on Nutrient Uptake, Use Efficiency and Yield in Different Rice (Oryza sativa L.) Establishment Methods under Nutrient Management Practices
Authors: Poojitha K. , Denesh G. R.
Published: September 2022

The experiment was conducted at Zonal Agricultural Research Station, Vishwesharaiah Canal Farm, Mandya during 2018-19 to study the nutrient uptake (NPK), use efficiency and grain yield of rice (Oryza sativa L.) in different establishment methods under varied nutrient management practices. The experiment was laid out in a split plot design with three replications. The main plot comprised of three establishment methods viz., semi dry rice, drum seeded rice and transplanted rice and whereas the subplot had five nutrient management practices. The nitrogen, phosphorous and potash uptake by rice plant in grain, straw and total was statistically on par among establishment methods. Further, the application of 150% Recommended dose of inorganic fertilizers (RDIF) recorded significantly higher total nitrogen, phosphorus and potassium uptake. Among establishment methods, significantly higher Nitrogen Use Efficiency (NUE) was recorded in transplanted rice (64.40 kg kg-1), but Phosphorus Use Efficiency (PUE) (88.38 to 101.72 kg kg-1) and Potassium Use Efficiency (KUE) (114.76 to 129.82 kg kg-1) recorded were statistically at par between establishment methods. The significantly higher NUE (90.73 kg kg-1) in Leaf Color Chart (LCC) based nitrogen management, PUE (108.36 kg kg-1) in nutrient management as per UAS (B) package of practices and KUE (149.16 kg kg-1) in 100% RDIF treatments. The grain yield recoded was at par among rice establishment methods (5521 to 6242 kg ha-1), however was superior in nutrient management with 150% RDIF (6687 kg ha-1).
Customer Relationship Management, Innovation Capability, Technological Environment, and Performance of Small and Medium Scale Enterprises: A Research Framework and Proposition
Authors: Tuamyil Rufina Betzoom , Gontur Silas , Davireng Makrop
Published: September 2022

This study looked into the consequences of customer relationship management by creating empirical evidence grounded in relationship marketing theory and dynamic capability theory. The study proposed a direct as well as an indirect relationship between customer relationship management and firm performance, recognizing technological environment as the interacting variables of customer relationship management that influences the performance of small and medium scale enterprises (SMEs), suggesting that technology environment as a moderator in the customer relationship management model. The study explained the theoretical and practical contributions of the model in our understanding of customer relationship management practices and the intervening role of innovation capability. Technological environment was also discussed especially from the perspective of SMEs.
Inflation Rate Volatility and Household Final Consumption Expenditure: Evidence from Cameroon
Authors: Ewane Enongene Betrand , Abonongi Andigema Snota
Published: September 2022

Aims: The study aims to examine the effects of inflation rate volatility on household final consumption expenditure in Cameroon. Studies on inflation rate and household final consumption expenditure in Cameroon are limited. This study provides a new insight into how inflation rate fluctuations affect household consumption expenditure in Cameroon.

Study Design: The study made use of an ex-post facto research design as the researcher has no control over the variables.

Place and Duration of the Study: The study was conducted in Cameroon using World Bank data from 1980-2020.

Methodology of the Study: The objectives of the study were accomplished using the autoregressive distributive lag (ARDL) bound test and error correction model (ECM) based on the conclusion of the unit root test.

Results: The findings indicate that the inflation rate has a positive and significant effect on household final consumption expenditure in both the short and long run.

Conclusion: The study concludes that an unstable inflation rate has a great impact on household final consumption expenditure in Cameroon.
Impact of Watershed Management on Stream Flow and Build-up Water Storage in Parasai-Sindh Watershed of SAT Region, India
Authors: Kumari Reena , Sharma Babloo , Kumari Pratibha
Published: September 2022

Aims: The study of runoff and base flow estimates and their impact on groundwater status in the semi-arid region of India is typically limited. We are focused on runoff and base flow in the Parasai-Sindh watershed, and impact of rain water harvesting structure on harvesting of stream flow and change ground water status.

Place and Duration of Study: The study site is located in Jhansi district (Bundelkhand region) of Uttar Pradesh and started from 2012 and completed at end of 2013.

Methodology: Total six rainwater harvesting structure (RHS) or checkdams were constructed on the drainage line from ridge to final outlet of watershed. Daily rainfall data was observed with automatic rain gauge during the study period. For discharge estimation, the runoff gauging station was installed at the outlet of watershed. The runoff and base flow of watershed were estimated by subtracting barometric pressure from the stage recoded by Baro and Diver install at outlet to get actual stage of runoff passing over it. The water pressure head of 200 randomly selected open wells were monitored on monthly interval.

Results: The geological area of watershed is 12.46 km2 and it’s main stream is found to be of 4th order. The results indicate that out of 49.2 mm rainfall event, runoff and base flow at outlet of watershed were found as 20.98% and 4.19%, respectively. Whereas, runoff and base flow were recorded 14.12% and 11.18%, respectively against 86.2 mm rainfall. Total runoff and base flow produced from outlet was recorded as 16 and 7%, respectively. The water head pressure of open wells was improved 92.45% after the rainy season as compared to before the rainy season.

Conclusion: The findings of the study are useful and show relationship between rainfall: runoff and estimation of base flow separation from the total discharge at the outlet of watershed. The estimation of volume of runoff which was harvested as surface runoff during rainy season and it's indirectly effected groundwater recharging through construction of RHS in ephemeral drain of Bundelkhand region.
A Polyherbal Formulation Katakakhadiradi Kashayam in Treatment of Diabetes – Review
Authors: Jessica S. Angelie , Kavimani M. , Prabhu K. , Ramadoss Mukilan , Sathish Kumar M. , Amalraj Julie Christy , Dhamodharan Jagadeesh
Published: September 2022

Diabetes is a common non-transmittable disease in the world today. It is the fourth leading  cause of mortality in most developed nations and there is significant proof that it is widespread   in many developing and newly developed nations. Diabetes patients are at risk of developing  is chemic heart disease, cerebrovascular disease and peripheral vascular disease, all of which can result in severe morbidity and death. The most widely used alternative therapy for glycaemic control is herbal medication. The effectiveness of botanicals in lowering sugar levels has been confirmed scientifically for a variety of Indian plant species. Numerous plants have been shown to be effective in treating a variety of systemic illnesses in traditional medical systems. Although many traditional/indigenous medical systems are more effective than modern medications, one of the biggest problems facing traditional medicine is the absence of comprehensive standardisation. The antioxidant, anti-inflammatory and hepatoprotective qualities of Katakakhadiradi kashayam may be responsible for its antidiabetic effects, but further  research is needed to fully comprehend this kashayam's protective effects against a variety  of ailments.
Role of Herbal Medicines in Hepatocellular Carcinoma
Authors: Javed Faryal , Zubair Summiya , Imran Hassan , Munir Safia Sultana , Riaz Humayun , Sultana Misbah , Kayani Ruqaiya Rasheed , Manzoor Saba , Nazir Saeed Ur Rashid , Ali Muhammad Maaz
Published: September 2022

Mutation in several factors and pathways leads to the development of hepatic cancer i.e. Mutation in Wnt-β-Catenin Signalling Pathway , activation of the Insulin-Like Growth Factor (IGF) Signalling Pathway, The P13/PTEN/AKT, TP53 Tumour Suppressor Gene. Liver cirrhosis and fatty liver predispose the normal tissues to fibrosis leading to liver cancer. Excessive alcohol intake results in the inflammation of liver proceeding to cirrhosis and ultimately hepatic carcinoma. Hepatocellular Carcinoma (HCC) is multi-centric i.e. has huge variability in its spread which differs from person to person. Four approaches are practiced for treatment of hepatic cancer; surgery, transarterial intervention, percutaneous intervention, and drug approach. Surgery includes liver transplant and tumour resection. Transarterial approach includes chemoembolization and embolization. Percutaneous approach includes radiofrequency thermal ablation (RFTA) and ethanol injection. Drugs are various including herbal plant medicines, herbal formulae, synthetic drugs, immune, and gene therapies. Zingiber officinal, Schinus molle L., Zerumbone, Curcuma longa and Mammea siamensis are some of the plant medicines.
Nickel Supported Parangtritis Beach Sand (PP) Catalyst for Hydrocracking of Palm and Malapari Oil into Biofuel
Authors: Ibrahim Muh. Siddik , Trisunaryanti Wega , Triyono Triyono
Published: September 2022

Nickel supported Parangtritis beach sand (PP) catalyst for hydrocracking of palm and malapari oil into biofuel has been conducted. The impregnation process of Nickel (Ni) metal on PP was carried out through the dry impregnation method (blending) using a precursor salt of NiCl2.6H2O with variations of Ni metal as much as 10 and 15 wt% of PP which produced Ni(A) and Ni(B) catalysts. Each catalyst was tested for activity and selectivity through the hydrocracking process of oil into biofuel using a semi-batch system reactor at a temperature of 450 oC, a hydrogen gas flow rate of 20 mL/minute for 2 hours, and a weight ratio of 1:200 catalyst:feed (w/w). The results showed that the Ni(A)/PP catalyst had the highest activity and selectivity with the yield of liquid products and the total biofuel fraction (biohydrocarbons) obtained from hydrocracking of palm oil of 68.50 and 49.87 wt%, respectively. Ni(A)/PP catalyst has a total acidity, surface area, and crystal size of 0.051 mmol/g, 4.44 m2/g, 25.86 nm, respectively. The reusability test of the Ni(A)/PP catalyst in the hydrocracking process of palm oil into biofuel after the third use resulted in a liquid product and the total biofuel fraction obtained was 64.20 and 41.46 wt%, respectively. The yield of liquid product and the total fraction of biofuel (biohydrocarbon) in hydrocracking malapari oil were 66.10, 47.83 wt%, respectively. Copyright © 2022 by Authors, Published by BCREC Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).
Association of Research and Development Investments With Treatment Costs for New Drugs Approved From 2009 to 2018
Authors: Wouters Olivier J. , Berenbrok Lucas A. , He Meiqi , Li Yihan , Hernandez Inmaculada
Published: September 2022

Importance

Drug companies frequently claim that high prices are needed to recoup spending on research and development. If high research and development costs justified high drug prices, then an association between these 2 measures would be expected.

Objective

To examine the association between treatment costs and research and development investments for new therapeutic agents approved by the US Food and Drug Administration (FDA) from 2009 to 2018.

Design, Setting, and Participants

This cross-sectional study analyzed 60 drugs approved by the FDA between January 1, 2009, and December 31, 2018, for which data on research and development investments and list or net prices were available. Data sources included the FDA and SSR Health databases.

Main Outcomes and Measures

The primary independent variable was estimated research and development investment. The outcome was standardized treatment costs (ie, annual treatment costs for both chronic and cycle drugs, and treatment costs for the maximum length of treatment recommended for acute drugs). Standardized treatment costs were estimated separately using list and net prices obtained from SSR Health at the time of launch and in 2021. To test the association between research and development investments and treatment costs, correlation coefficients were estimated and linear regression models were fitted that controlled for other factors that were associated with treatment costs, such as orphan status. Two models were used: a fully adjusted model that was adjusted for all variables in the data set associated with treatment costs and a parsimonious model in which highly correlated variables were excluded.

Results

No correlation was observed between estimated research and development investments and log-adjusted treatment costs based on list prices at launch (R = −0.02 and R2 = 0.0005; P = .87) or net prices 1 year after launch (R = 0.08 and R2 = 0.007; P = .73). This result held when 2021 prices were used to estimate treatment costs. The linear regression models showed no association between estimated research and development investments and log-adjusted treatment costs at launch (β = 0.002 [95% CI, −0.02 to 0.02; P = .84] in the fully adjusted model; β = 0.01 [95% CI, −0.01 to 0.03; P = .46] in the parsimonious model) or from 2021 (β = −0.01 [95% CI, −0.03 to 0.01; P = .30] in the fully adjusted model; β = −0.004 [95% CI, −0.02 to 0.02; P = .66] in the parsimonious model).

Conclusions and Relevance

Results of this study indicated that research and development investments did not explain the variation in list prices for the 60 drugs in this sample. Drug companies should make further data available to support their claims that high drug prices are needed to recover research and development investments, if they are to continue to use this argument to justify high prices.
A Bill of Children’s Digital Rights Is Required to Improve and Sustain Children’s Futures Globally
Authors: Roman-Urrestarazu Andres , Kinsey Jane , van Kessel Robin
Published: September 2022

This Viewpoint calls for policy action, such as a comprehensive Bill of Children’s Digital Rights, that would embrace rights allowing children and young people to access the digital infrastructure and interact with digital media safely.
Risk of COVID‐19 Among Unvaccinated and Vaccinated Patients With Rheumatoid Arthritis: A General Population Study
Authors: Li Hui , Wallace Zachary S. , Sparks Jeffrey A. , Lu Na , Wei Jie , Xie Dongxing , Wang Yilun , Zeng Chao , Lei Guanghua , Zhang Yuqing
Published: September 2022

Objective

To determine whether patients with rheumatoid arthritis (RA) are at higher risks for SARS–CoV‐2 infection and its severe outcomes before and after COVID‐19 vaccination.

Methods

Using a UK primary care database, we conducted 2 cohort studies to compare the risks of SARS–CoV‐2 infection, hospitalization, and death from COVID‐19 between patients with RA and the general population according to their COVID‐19 vaccination status. We used exposure score overlap weighting to balance baseline characteristics between 2 comparison cohorts.

Results

Among unvaccinated individuals, the weighted incidence rates of SARS–CoV‐2 infection (9.21 versus 8.16 of 1,000 person‐months), hospitalization (3.46 versus 2.14 of 1,000 person‐months), and death (1.19 versus 0.62 of 1,000 person‐months) were higher among patients with RA than the general population over 3 months of follow‐up; the corresponding adjusted hazard ratios (HRs) were 1.10 (95% confidence interval [95% CI] 1.00–1.24), 1.62 (95% CI 1.34–1.96), and 1.88 (95% CI 1.37–2.60), respectively. Among vaccinated individuals, the weighted rates of breakthrough infection (4.17 versus 3.96 of 1,000 person‐months; HR 1.10 [95% CI 1.00–1.20]) and hospitalization (0.42 versus 0.32 of 1,000 person‐months; HR 1.29 [95% CI 0.96–1.75]) were higher among patients with RA than the general population over 9 months of follow‐up; however, no apparent difference in the risk of these outcomes was observed over 3 and 6 months of follow‐up between 2 comparison cohorts.

Conclusion

Patients with RA are still at higher risks of SARS–CoV‐2 infection and COVID‐19 hospitalization than the general population after receiving COVID‐19 vaccines. These findings support booster COVID‐19 vaccinations and adherence of other preventive strategies among patients with RA.
Multi‐Responsive Jammed Micro‐Gels Ink: Toward Control over the Resolution and the Stability of 3D Printed Scaffolds
Authors: Es Sayed Julien , Khoonkari Mohammad , Oggioni Marta , Perrin Patrick , Sanson Nicolas , Kamperman Marleen , Włodarczyk‐Biegun Małgorzata Katarzyna
Published: September 2022

3D printing of hydrogels usually relies on a combination of fine‐tuned material chemistry and polymer chain architecture to obtain an ink with adequate yield‐stress flow, shear‐thinning, and self‐healing behavior. Recent approaches in hydrogel ink design include introduction of reversible covalent or supramolecular bonds or jamming of microparticles into a granular hydrogel. However, the dimensional stability of such systems is typically afforded by a post‐printing covalent cross‐linking step that impedes further on‐demand degradation of the scaffolds. Here, a jammed micro‐gels ink made of thermosensitive poly(N‐isopropylacrylamide) micro‐gels incorporating terpyridine ligand linkers are proposed as a 3D printable ink that is cured post‐printing by iron (II) cations for long‐term stabilization. The uncross‐linked micro‐gels ink exhibits the rheological characteristics of granular materials, meaning yield‐stress, shear‐thinning and fast recovery. Upon curing, iron (II)‐bis‐terpyridine coordination complexes between neighboring micro‐gels are formed. The supramolecular bonds are sufficiently strong and long‐lived to maintain scaffold integrity during manual handling or immersion in liquid medium for over two months. The thermosensitivity of the micro‐gels endows the printed construct with reversible and cyclable temperature‐induced resolution enhancement, while the supramolecular cross‐linking provides an asset of disintegration on‐demand. The proposed micro‐gel scaffolds are biocompatible, revealing the potential for biomedical applications and 4D bioprinting.
A New Strategy of Coupling Pyroelectric and Piezoelectric Effects for Photoresponse Enhancement of a Cu(In,Ga)Se2 Heterojunction Photodetector
Authors: Liu Jihong , Liang Zidong , Chen Jingwei , Wang Shufang , Pan Caofeng , Qiao Shuang
Published: September 2022

Pyro/piezoelectric effects are thought as essential ways to modulate photoresponses of optoelectronic devices, but the pyro/piezoelectric materials usually function as photoactive or fundamental band matching layers. In this manuscript, a Cu(In,Ga)Se2 (CIGS) multilayer heterojunction of Glass/Mo/CIGS/CdS/ZnO nanowire/ITO is prepared as a self‐powered photodetector (PD). The PD exhibits excellent performances in 405 to 1064 nm with maximum responsivity (R) of 0.455 A W−1, and detectivity (D) of 7.22 × 1011 Jones at zero bias. More importantly, the temperature variation‐induced pyroelectric field in the non‐photoactive ZnO layer is demonstrated to facilitate the transport of carriers. After introducing the pyroelectric effect, the responsivity (R) and detectivity (D) are largely increased to 4.92 A W−1 and 7.81 × 1012 Jones, respectively, and an ultrafast response time of 67.13/78.57 µs is obtained. Meanwhile, the response wavelength is extended to 1550 nm, which is far beyond the spectral limitation of the heterojunction. Besides, the piezoelectric effect of the ZnO nanowire can further optimize the band alignment and then boost the photovoltaic and pyroelectric responses. Owning to the favorable three‐synergistic mechanisms, the best R of 7.22 A W−1 and D of 1.17 × 1013 Jones are observed, which are enhanced by 1586.8% and 1620.5%, respectively, and the response time is also shortened to 50.17/60.65 µs.
3D‐Bioassembly of VH‐Spheroids for Cartilage Regeneration: in Vitro Evaluation of Chondrogenesis, Fusion and Lateral Integration
Authors: Veenendaal Laura , Longoni Alessia , Hooper Gary J. , Lim Khoon S. , Woodfield Tim B. F. , Lindberg Gabriella C. J.
Published: September 2022

Lateral integration and fusion of cartilage tissue interfaces remain significantly challenging and limits success of cartilage tissue engineering (TE) strategies. In this study, self‐assembled vitreous humor (VH) spheroids are fabricated by seeding clinically relevant human articular chondrocytes (hACs) or human mesenchymal stromal cells (hMSCs) in four VH hydrogels with different glycosaminoglycans (GAG) and protein content. Quantitative and qualitative analysis of the VH spheroids revealed that hAC‐VH spheroids are dependent on the initial GAG content of VH hydrogels to achieve successful chondrogenesis. Remarkably, uniform GAG and collagen type II distribution is found in all hMSC‐VH spheroids, independent of the VH donor. HMSC‐VH spheroids are therefore further evaluated for downstream applications by tracking cellular migration, and evaluating neotissue formation at the tissue‐tissue interface of cartilage spheroids 3D‐bioassembled into an in vitro fusion model to asses fusion and integration. hMSC‐VH spheroids enhanced multidirectional cellular migration of both hACs and hMSCs toward the tissue‐tissue interface, and consequently supported dense GAG and collagen type II deposition at the integration region. Ultimately, hMSC‐seeded VH spheroids display successful chondrogenesis and endorse fusion and integration of cartilage tissue interfaces through upregulated cellular migration of clinically relevant cell sources – key elements for clinical translation of cell‐based TE strategies.
Intrinsically Conductive Liquid Metal‐Elastomer Composites for Stretchable and Flexible Electronics
Authors: Schlingman Kory , D'Amaral Gloria M. , Carmichael R. Stephen , Carmichael Tricia Breen
Published: September 2022

Liquid metal‐embedded elastomers (LMEEs) are a class of deformable composites made of particles of liquid metal dispersed in an elastomeric matrix. Although these composites possess high thermal conductivity, they are not intrinsically electrically conductive unless a stimulus is applied to join the liquid metal inclusions into a conductive pathway. LMEEs with intrinsic conductivity, especially with a conductive surface, have great potential uses in flexible and stretchable electronics as soft, nondamaging contacts for device characterization, stretchable interconnects for deformable circuits, and as a “soft solder” to electrically connect devices to flexible and stretchable substrates. Here, a simple process is introduced to fabricate intrinsically conductive LMEEs (iLMEEs) with conductive surfaces through the sedimentation of microparticles of eutectic gallium‐indium alloy (EGaIn) in the elastomer poly(dimethylsiloxane). During this sedimentation process, an EGaIn‐rich 3D percolation network forms at the bottom surface. The resulting iLMEE possesses a conductive surface comprising a mosaic of EGaIn particles embedded in PDMS, with a low sheet resistance of 0.63 ± 0.04 Ω sq–1. iLMEE is soft, stretchable, and exhibits stable conductivity to 100% strain. We demonstrate the use of iLMEE as nondamaging, reusable soft electrical contact probes and as mechanically robust electrical connections between light‐emitting devices and flexible plastic substrates.
Development of Reflow Fill of CGeSbTe Films for Sub‐20 nm Cells in 3D Cross‐Point Memory
Authors: Park Jeonghee , Wu Zhe , Park Jiho , Kim Jonguk , Kuh Bongjin , Lee Jongmyeong , Hwang Seungwoo , Han Seungwu
Published: September 2022

To obtain reliable and scalable cells in 3D cross‐point memory, endurance failures caused by voiding from etching damage to memory cells should be resolved to preserve the properties of GeSbTe (GST) phase‐change materials. Herein, the fabrication of a damascene cell without patterning, which relies on the bottom‐up fill of carbon‐doped GST layers into confined cells, is proposed as a promising solution. The reflow fill of the sputtered carbon‐doped GST films into confined cells at high‐temperature and low‐power conditions is demonstrated, and a mechanism in which Sb and Te transfer into the cell through vapor transfer and viscous flow due to capillary pressure is verified. The aspect ratio increases from 2 to 7.7 under enhanced vaporization of Sb and Te as well as the capillary force. The advanced reflow‐fill process using a laser can overcome the limit of the conventional reflow‐fill technology by increasing the atomic mobility above the melting temperature. Based on the proposed method, 19 nm cross‐point memory devices are successfully integrated together with the Ovonyx threshold switch and appropriate memory windows are secured. Furthermore, the 9 nm cells exhibit reliable endurance cycles over 108.
ε‐Ga2O3: An Emerging Wide Bandgap Piezoelectric Semiconductor for Application in Radio Frequency Resonators
Authors: Chen Zimin , Lu Xing , Tu Yujia , Chen Weiqu , Zhang Zhipeng , Cheng Shengliang , Chen Shujian , Luo Hongtai , He Zhiyuan , Pei Yanli , Wang Gang
Published: September 2022

The explosion of mobile data from the internet of things (IoT) is leading to the emergence of 5G technology with dramatic frequency band expansion and efficient band allocations. Along with this, the demand for high‐performance filters for 5G radio frequency (RF) front‐ends keeps growing. The most popular 5G filters are constructed by piezoelectric resonators based on AlN semiconductor. However, AlN possesses a piezoelectric constant d33 lower than 5 pm V−1 and it becomes necessary to develop novel semiconductors with larger piezoelectric constant. In this work, it is shown that strong piezoelectricity exists in ε‐Ga2O3. High‐quality phase‐pure ε‐Ga2O3 thin films with a relatively low residual stress are prepared. A switching spectroscopy piezoelectric force microscope (SS‐PFM) measurement is carried out and the piezoelectric constant d33 of ε‐Ga2O3 is determined to be ≈10.8–11.2 pm V−1, which is twice as large as that of AlN. For the first time, surface acoustic wave (SAW) resonators are demonstrated on the ε‐Ga2O3 thin films and different vibration modes resonating in the GHz range are observed. The results suggest that ε‐Ga2O3 is a great material candidate for application in piezoelectric devices, thanks to its wide bandgap, strong piezoelectric property, small acoustic impedance, and low residual stress.
N,S‐Doped Porous Carbon Nanobelts Embedded with MoS2 Nanosheets as a Self‐Standing Host for Dendrite‐Free Li Metal Anodes
Authors: Li Binke , Cao Weishan , Wang Shuaize , Cao Zhenjiang , Shi Yongzheng , Niu Jin , Wang Feng
Published: September 2022

Metallic Li is one of the most promising anodes for high‐energy secondary batteries. However, the enormous volume changes and severe dendrite formation during the Li plating/stripping process hinder the practical application of Li metal anodes (LMAs). We have developed a sulfate‐assisted strategy to synthesize a self‐standing host composed of N,S‐doped porous carbon nanobelts embedded with MoS2 nanosheets (MoS2@NSPCB) for use in LMAs. In situ measurements and theoretical calculations reveal that the uniformly distributed MoS2 derivatives within the carbon nanobelts serve as stable lithiophilic sites which effectively homogenize Li nucleation and suppress dendrite formation. In addition, the hierarchical porosity and 3D nanobelt networks ensure fast Li‐ion diffusion and accommodate the volume change of Li deposits during the plating/stripping process. As a result, a Li–Li symmetric cell using the MoS2@NSPCB host operates steadily over 1500 h with an ultralow voltage hysteresis (≈24.2 mV) at 3 mA cm−2/3 mAh cm−2. When paired with a LiFePO4 cathode, the current collector‐free LMA endows the full cell with a high energy density of 460 Wh kg−1 and good cycling performance (with a capacity retention of ≈70% even after 1600 cycles at 10 C).
High β‐phase Poly(vinylidene fluoride) Using a Thermally Decomposable Molecular Splint
Authors: Choi Jinwoo , Lee Kyuho , Lee Minhwan , Kim Taebin , Eom Sangwon , Sim Jae Hyun , Lee Won Bo , Kim YongJoo , Park Cheolmin , Kang Youngjong
Published: September 2022

An additive, 1,4‐butadiene sulfone (BDS), which generates H2SO3 by in situ thermal retro‐Diels‐Alder decompositions, is used for preparing high β‐phase polyvinylidene fluoride (PVDF) films. Because of preferential multiple non‐covalent interactions of H2SO3 with all‐trans configuration of PVDF, β‐phase PVDF is spontaneously induced without mechanical drawing and/or extensive thermal annealing process. PVDF films cast from PVDF/BDS/water solutions exhibit high β‐phase content (fβ = 95%) when the BDS concentration is only cBDS = 1.0 wt%, which is confirmed by polarized optical microscopy (POM), SEM, Fourier transform infrared spectroscopy (FT‐IR), differential scan calorimetry (DSC), and 2D grazing incidence wide‐angle X‐ray scattering (GIWAXS). Because of the high β‐phase content, PVDF films prepared by using BDS exhibit excellent ferroelectric and piezoelectric properties (Ec = 50 MV/m, Pr = 5 µC/cm2, and d33 = ≈‐25 pm/V). Furthermore, a triboelectric nanogenerator (TENG) developed with high β‐phase PVDF film exhibits enhanced performance as 2.5 times higher than neat PVDF film in output charge density, allowing reliable operation of conventional electronic devices.
Dual‐Gate Anti‐Ambipolar Transistor with Van der Waals ReS2/WSe2Heterojunction for Reconfigurable Logic Operations
Authors: Shingaya Yoshitaka , Zulkefli Amir , Iwasaki Takuya , Hayakawa Ryoma , Nakaharai Shu , Watanabe Kenji , Taniguchi Takashi , Wakayama Yutaka
Published: September 2022

A dual‐gate anti‐ambipolar transistor (AAT) with a two‐dimensional ReS2and WSe2heterojunction is developed. The characteristic Λ‐shaped transfer curves yielded by the bottom‐gate voltage are effectively controlled by the top‐gate voltage. This feature is applied to logic operations, with the bottom‐ and top‐gate voltages acting as two input signals and the drain current (Id) monitored as an output signal. Importantly, a single dual‐gate AAT exhibits all the two‐input logic operations (AND, OR, XOR, NAND, NOR, and XNOR) under optimized input voltages. Additionally, drain voltage (Vd)‐induced switching between AND and OR logic operations is achieved. These features are advantageous for simplifying circuit design.